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Neuroscience › Neurology

Neurological Disease Mechanisms and Treatments

Works Count: 46680

Description

This cluster of papers focuses on chronic cerebral hypoperfusion and its association with neurodegenerative diseases, vascular cognitive impairment, white matter lesions, and oxidative stress. The research includes experimental models, glial activation, memory impairment, and the neuroprotective effects of various compounds.

Keywords

Cerebral Hypoperfusion; Vascular Cognitive Impairment; White Matter Lesions; Neurodegenerative Diseases; Experimental Models; Oxidative Stress; Glial Activation; Memory Impairment; Animal Models; Neuroprotective Effects

Intake of flavonoids and risk of dementia.

2000-01-01
Daniel Commenges , Virginie Scotet , S. Renaud +3 more

The neuropathology and cerebrovascular mechanisms of dementia

2015-07-15
Limor Raz , Janice E. Knoefel , Kiran Bhaskar
The prevalence of dementia is increasing in our aging population at an alarming rate. Because of the heterogeneity of clinical presentation and complexity of disease neuropathology, dementia classifications remain controversial. … The prevalence of dementia is increasing in our aging population at an alarming rate. Because of the heterogeneity of clinical presentation and complexity of disease neuropathology, dementia classifications remain controversial. Recently, the National Plan to address Alzheimer’s Disease prioritized Alzheimer’s disease-related dementias to include: Alzheimer’s disease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, and mixed dementias. While each of these dementing conditions has their unique pathologic signature, one common etiology shared among all these conditions is cerebrovascular dysfunction at some point during the disease process. The goal of this comprehensive review is to summarize the current findings in the field and address the important contributions of cerebrovascular, physiologic, and cellular alterations to cognitive impairment in these human dementias. Specifically, evidence will be presented in support of small-vessel disease as an underlying neuropathologic hallmark of various dementias, while controversial findings will also be highlighted. Finally, the molecular mechanisms shared among all dementia types including hypoxia, oxidative stress, mitochondrial bioenergetics, neuroinflammation, neurodegeneration, and blood–brain barrier permeability responsible for disease etiology and progression will be discussed.
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Memantine for dementia

2006-04-19
Rupert McShane , Almudena Areosa Sastre , Neda Minakaran

Hypertension and Cerebrovascular Dysfunction

2008-06-01
Costantino Iadecola , Robin L. Davisson
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Risk factors for progression of brain atrophy in aging

2005-05-24
Christian Enzinger , Franz Fazekas , Paul M. Matthews +4 more
<b>Objectives: </b> To determine the rate of brain atrophy in neurologically asymptomatic elderly and to investigate the impact of baseline variables including conventional cerebrovascular risk factors, <i>APOE</i> ε4, and white … <b>Objectives: </b> To determine the rate of brain atrophy in neurologically asymptomatic elderly and to investigate the impact of baseline variables including conventional cerebrovascular risk factors, <i>APOE</i> ε4, and white matter hyperintensity (WMH) on its progression. <b>Methods: </b> We assessed the brain parenchymal fraction at baseline and subsequent annual brain volume changes over 6 years for 201 participants (F/M = 96/105; 59.8 ± 5.9 years) in the Austrian Stroke Prevention Study from 1.5-T MRI scans using SIENA (structural image evaluation using normalization of atrophy)/SIENAX (an adaptation of SIENA for cross-sectional measurement)(www.fmrib.ox.ac.uk/fsl). Hypertension, cardiac disease, diabetes mellitus, smoking, and regular alcohol intake were present in 64 (31.8%), 60 (29.9%), 5 (2.5%), 70 (39.3%), and 40 (20.7%) subjects, respectively. Plasma levels of fasting glucose (93.7 ± 18.6 mg/dL), glycated hemoglobin A (HbA<sub>1c</sub>; 5.6 ± 0.7%), total cholesterol (228.3 ± 40.3 mg/dL), and triglycerides (127.0 ± 75.2 mg/dL) were determined. WMH was rated as absent (n = 56), punctate (n = 120), early confluent (n = 14), and confluent (n = 11). <b>Results: </b> The baseline brain parenchymal fraction of the entire cohort was 0.80 ± 0.02 with a mean annual brain volume change of −0.40 ± 0.29%. Univariate analysis demonstrated a higher rate of brain atrophy in older subjects (<i>p</i> = 0.0001), in those with higher HbA<sub>1c</sub> (<i>p</i> = 0.0001), higher body mass index (<i>p</i> = 0.02), high alcohol intake (<i>p</i> = 0.04), severe WMH (<i>p</i> = 0.03), and in <i>APOE</i> ε4 carriers (<i>p</i> = 0.07). Multivariate analysis suggested that baseline brain parenchymal fraction, HbA<sub>1c</sub>, and WMH score explain a major proportion of variance in the rates of brain atrophy in the cohort (corrected <i>R</i><sup>2</sup> = 0.27; <i>p</i> = 0.0001). <b>Conclusions: </b> Neurologically asymptomatic elderly experience continuing brain volume loss, which appears to accelerate with age. Glycated hemoglobin A (HbA<sub>1c</sub>) was identified as a risk factor for a greater rate of brain atrophy. Clustering of factors associated with the so-called metabolic syndrome in subjects with high HbA<sub>1c</sub> suggests a link between this syndrome and late-life brain tissue loss.

Barbiturate Protection in Acute Focal Cerebral Ischemia

1974-01-01
Allan L. Smith , Julian T. Hoff , Surl L. Nielsen +1 more
We have found that anesthetic technique modifies the neurological and pathological sequelae of unilateral middle cerebral artery and internal carotid artery occlusion in dogs. Occlusion was performed in seven groups … We have found that anesthetic technique modifies the neurological and pathological sequelae of unilateral middle cerebral artery and internal carotid artery occlusion in dogs. Occlusion was performed in seven groups of six dogs during each of the following anesthetic regimens: light (0.8%) halothane, "awake," deep (1.9%) halothane, deep halothane with mean arterial pressure reduced to 55 torr, pentobarbital (56 mg per kilogram), light halothane plus 40 mg per kilogram thiopental begun just before cerebral artery occlusion, and light halothane plus 40 mg per kilogram thiopental begun 15 minutes after occlusion. Body temperature, arterial P co co 2 P o o 2 pH, and blood pressure (except as noted above) were maintained normal. Neurological examinations were performed daily. On the seventh day the dogs were killed and their brains removed for pathological study. Hemiparesis occurred in five of six dogs under light halothane and five of six awake dogs; a mean of 10.8% and 9.6%, respectively, of their right hemispheres were infarcted. In the deep halothane groups, all of the normotensive and five of the six hypotensive dogs became severely hemiplegic; mean infarction size was 28.2% and 34.1%, respectively. Only one of the 18 dogs who received a barbiturate sustained a neurological deficit -- a transient unilateral weakness. Means of 1.4%, 2.7%, and 0.1% of the right hemisphere were infarcted in the barbiturate animals. The protective action of barbiturates in canine acute focal cerebral ischemia suggests that they should be considered for anesthesia in surgery requiring cerebral vessel occlusion and perhaps even for treatment of acute stroke.
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Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

2007-02-13
Stefan M. Gold , Isabel Dziobek , Victoria Sweat +7 more
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Pathogenetic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans.

1976-01-01
Yukio Yamori , Ryoichi Horie , Hajime Handa +2 more
The predilection sites of cerebrovascular lesions (cerebral hemorrhage and/or softening) were studied in 1,278 stroke-prone spontaneously hypertensive rats (SHRSP). The precise supply to the main cerebral arteries was determined by … The predilection sites of cerebrovascular lesions (cerebral hemorrhage and/or softening) were studied in 1,278 stroke-prone spontaneously hypertensive rats (SHRSP). The precise supply to the main cerebral arteries was determined by trypan blue injections and microangiography. The three major territories were the anteromedial cortex, the occipital cortex, and the basal ganglia. A common angioarchitectural characteristic of these three areas was the blood supply through "recurrent branching" from the main stream. In the basal ganglia, where there is a preponderance of lesions, the arteries responsible for these lesions belonged to the lateral group of lenticulostriate arteries. The primary pre-stroke arterial lesions were further studied microangiographically in SHRSP killed at the time the initial symptoms of stroke were detected. These points were located at the "boundary zone" of the main cerebral arteries. Our findings indicated the importance of these two angioarchitectural minor loci as the basis for functional or organic circulatory disturbances that may cause stroke. Since these local factors of stroke are common in the cortex and basal ganglia of rats and basal ganglia of humans, these SHRSP are regarded as good pathogenetic models for studies on stroke in humans.

Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

2015-01-01
Axel Montagne , Samuel Barnes , Melanie D. Sweeney +7 more
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Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment

2009-12-23
Robert Krikorian , Tiffany Nash , Marcelle D. Shidler +2 more
Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular … Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular pathology in individuals with CVD, and consumption of such flavonoid-containing foods is associated with a reduced risk for dementia. In addition, preliminary animal data have indicated improvement in memory and motor function with grape juice supplementation, suggesting potential for cognitive benefit in ageing humans. In this initial investigation of neurocognitive effects, we enrolled twelve older adults with memory decline but not dementia in a randomised, placebo-controlled, double-blind trial with Concord grape juice supplementation for 12 weeks. We observed significant improvement in a measure of verbal learning and non-significant enhancement of verbal and spatial recall. There was no appreciable effect of the intervention on depressive symptoms and no effect on weight or waist circumference. A small increase in fasting insulin was observed for those consuming grape juice. These preliminary findings suggest that supplementation with Concord grape juice may enhance cognitive function for older adults with early memory decline and establish a basis for more comprehensive investigations to evaluate potential benefit and assess mechanisms of action.
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The Pathobiology of Vascular Dementia

2013-11-01
Costantino Iadecola
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Neurovascular regulation in the normal brain and in Alzheimer's disease

2004-05-01
Costantino Iadecola

Risk Factors for Vascular Dementia and Alzheimer Disease

2004-09-17
Philip B. Gorelick
Alzheimer disease and vascular cognitive impairment are important causes of cognitive decline in the elderly. It has now been shown that vascular risk factors have measurable negative effects on the … Alzheimer disease and vascular cognitive impairment are important causes of cognitive decline in the elderly. It has now been shown that vascular risk factors have measurable negative effects on the brain and are associated with cognitive impairment. We review vascular factors that might be responsible to cognitive decline in Alzheimer disease and vascular cognitive impairment and the corresponding intervenvations that might prevent cognitive impairment as we age.
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Pathogenesis of Leukoaraiosis

1997-03-01
Leonardo Pantoni , Julio Herrero García
Background Changes in the cerebral hemispheric white matter, detectable with increasing frequency by modern neuroimaging methods, are associated with aging and conceivably may contribute to the development of specific cognitive … Background Changes in the cerebral hemispheric white matter, detectable with increasing frequency by modern neuroimaging methods, are associated with aging and conceivably may contribute to the development of specific cognitive deficits. The pathogenesis of these cerebral white matter abnormalities (sometimes described as leukoaraiosis) is unknown. This review evaluates the available evidence in support of the hypothesis that the etiology of leukoaraiosis is related to a specific type of cerebral ischemia and highlights mechanisms by which ischemic injury to the brain may induce selected structural alterations limited to the cerebral white matter. Summary of Review The review is based on the critical analysis of over 100 publications (most appearing in the last decade) dealing with the anatomy and physiology of the arterial circulation to the cerebral white matter and with the pathogenesis of leukoaraiosis. Conclusions A significant number of clues support the hypothesis that some types of leukoaraiosis may be the result of ischemic injury to the brain. Structural changes affecting the small intraparenchymal cerebral arteries and arterioles that are associated with aging and with stroke risk factors, altered cerebral blood flow autoregulation, and the conditions created by the unique arterial blood supply of the hemispheric white matter each seem to contribute to the development of leukoaraiosis. To the best of our ability to interpret current information, the type of ischemic injury that is most likely responsible for these white matter changes involves transient repeated events characterized by moderate drops in regional cerebral blood flow that induce an incomplete form of infarction. This hypothesis could be tested in appropriate experimental models.
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Cardiovascular Risk Factors Promote Brain Hypoperfusion Leading to Cognitive Decline and Dementia

2012-12-03
Jack C. de la Torre
Heart disease is the major leading cause of death and disability in the world. Mainly affecting the elderly population, heart disease and its main outcome, cardiovascular disease, have become an … Heart disease is the major leading cause of death and disability in the world. Mainly affecting the elderly population, heart disease and its main outcome, cardiovascular disease, have become an important risk factor in the development of cognitive decline and Alzheimer’s disease (AD). This paper examines the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular deficits in the development of cognitive impairment preceding AD. The evidence indicates a strong association between AD and cardiovascular risk factors, including ApoE 4 , atrial fibrillation, thrombotic events, hypertension, hypotension, heart failure, high serum markers of inflammation, coronary artery disease, low cardiac index, and valvular pathology. In elderly people whose cerebral perfusion is already diminished by their advanced age, additional reduction of cerebral blood flow stemming from abnormalities in the heart-brain vascular loop ostensibly increases the probability of developing AD. Evidence also suggests that a neuronal energy crisis brought on by relentless brain hypoperfusion may be responsible for protein synthesis abnormalities that later result in the classic neurodegenerative lesions involving the formation of amyloid-beta plaques and neurofibrillary tangles. Insight into how cardiovascular risk factors can induce progressive cognitive impairment offers an enhanced understanding of the multifactorial pathophysiology characterizing AD and ways at preventing or managing the cardiovascular precursors of this dementia.
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Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI

2003-11-01
Tom den Heijer , S. E. Vermeer , Ewoud J. van Dijk +4 more
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Focal Brain Ischemia in the Rat: Methods for Reproducible Neocortical Infarction Using Tandem Occlusion of the Distal Middle Cerebral and Ipsilateral Common Carotid Arteries

1988-08-01
Steve Brint , Michael Jacewicz , Marika Kiessling +2 more
This article describes a 3-year experience with focal neocortical ischemia in three rat strains. Multiple groups of adult Wistar (n = 50), Fisher 344 (n = 31), and spontaneously hypertensive … This article describes a 3-year experience with focal neocortical ischemia in three rat strains. Multiple groups of adult Wistar (n = 50), Fisher 344 (n = 31), and spontaneously hypertensive (n = 72) rats were subjected to permanent occlusion of the distal middle cerebral (MCA) and ipsilateral common carotid arteries (CCA). Twenty-four hours later the animals were killed, and frozen brain sections were stained with hematoxylin and eosin to demarcate infarcted tissue. The infarct volume for each section was quantified with an image analyzer, and the total infarct volume was calculated with an iterative program that summed all interval volumes. Neocortical infarct volume was the largest and most reproducible in the spontaneously hypertensive rats (SHR). Statistical power analysis to project the numbers of animals necessary to detect a 25 or 50% change in infarct volume with α = 0.05 and β = 0.2 revealed that only the SHR model was practical in terms of requisite animals: i.e., &lt;10 animals per group. Tandem occlusion of the distal MCA and ipsilateral CCA in the SHR strain provides a surgically simple method for causing large neocortical infarcts with reproducible topography and volume. The interanimal variability in infarct volume that occurs even in the SHR strain dictates that randomized, concomitant controls are necessary in each study to ensure the accurate assessment of experimental manipulations or pharmacologic therapies.

Cerebral microvascular pathology in aging and Alzheimer's disease

2001-08-01
Eszter Farkas , Paul G.M. Luiten

The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia

2010-07-11
Costantino Iadecola

The expression, localization and functional significance of β-nerve growth factor in the central nervous system

1987-11-01
Scott R. Whittemore , Åke Seiger

The Quantification of Cerebral Infarction following Focal Ischemia in the Rat: Influence of Strain, Arterial Pressure, Blood Glucose Concentration, and Age

1988-08-01
D. Duverger , Eric T. MacKenzie
Focal cerebral ischemia was induced by occlusion of the middle cerebral artery in rats. The volumetric assessment of infarcted tissue, 2 days following occlusion, was calculated from the examination of … Focal cerebral ischemia was induced by occlusion of the middle cerebral artery in rats. The volumetric assessment of infarcted tissue, 2 days following occlusion, was calculated from the examination of eight preselected coronal sections. Five differing rat strains were examined. A small and variable infarcted volume was seen in Wistar-Kyoto rats; Sprague-Dawley rats had a relatively large, but still variable, infarcted volume. Of the normotensive rat strains, the most reproducible volume of infarcted tissue was seen in Fischer-344 rats; also the absolute value of the infarcted volume did not vary from one series to another in this strain. Chronic arterial hypertension, studied in both normal and stroke-prone spontaneously hypertensive rats, was associated with significantly larger infarction volumes. Age does not change the volume of necrosis: Fischer-344 rats were studied at 3, 9, and 20 months of age, and no significant differences were noted between these ages. Experimental diabetes was induced by the administration of streptozotocin 3 days prior to middle cerebral artery occlusion. Severe hyperglycemia (&gt;400 mg/dl) was associated with a considerably increased volume of infarction. The variability of the resultant lesion is high in the most commonly studied strains, but our results suggest that, for studies in normotensive rats, the use of the Fischer-344 strain produces a standardized and repeatable infarction that may be significantly modified by experimental interventions. Age is not a factor that affects the occlusion-induced infarction; in contrast, both chronic arterial hypertension and experimental diabetes aggravate the histological consequences of middle cerebral artery occlusion in the rat. We conclude that quantitative histological evaluation of infarct size allows a meaningful assessment of the gravity of focal cerebral ischemia.

Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review

2014-08-24
Stefan L.C. Geijselaers , Simone J. S. Sep , Coen D.A. Stehouwer +1 more

Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's disease

2005-07-02
Taufika Islam Williams , Bert C. Lynn , William R. Markesbery +1 more

Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions

2013-10-18
Geert Jan Biessels , Mark W. J. Strachan , Frank L.J. Visseren +2 more

Brain Magnetic Resonance Imaging Correlates of Impaired Cognition in Patients With Type 2 Diabetes

2006-04-01
S.M. Manschot , Augustina M.A. Brands , Jeroen van der Grond +4 more
The structural correlates of impaired cognition in type 2 diabetes are unclear. The present study compared cognition and brain magnetic resonance imaging (MRI) between type 2 diabetic patients and nondiabetic … The structural correlates of impaired cognition in type 2 diabetes are unclear. The present study compared cognition and brain magnetic resonance imaging (MRI) between type 2 diabetic patients and nondiabetic control subjects and assessed the relationship between cognition and MRI findings and blood pressure and metabolic control. The study included 113 patients and 51 control subjects. Brain MRI scans were rated for white matter lesions (WMLs), cortical and subcortical atrophy, and infarcts. Neuropsychological test scores were divided into five cognitive domains and expressed as standardized Z values. Type 2 diabetes was associated with deep WMLs (P = 0.02), cortical (P &amp;lt; 0.001) and subcortical (P &amp;lt; 0.05) atrophy, (silent) infarcts (P = 0.06), and impaired cognitive performance (attention and executive function, information-processing speed, and memory, all P &amp;lt; 0.05). Adjustment for hypertension did not affect the results. Within the type 2 diabetic group, cognitive function was inversely related with WMLs, atrophy, and the presence of infarcts (adjusted for age, sex, and estimated IQ), and there was a modest association with HbA1c and diabetes duration. This association was strongest for age, even more so than in control subjects. We conclude that cognitive impairments in patients with type 2 diabetes are not only associated with subcortical ischemic changes in the brain, but also with increased brain atrophy.
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White Matter Lesions and Glial Activation in a Novel Mouse Model of Chronic Cerebral Hypoperfusion

2004-10-08
Masunari Shibata , Ryo Ohtani , Masafumi Ihara +1 more
Cerebrovascular white matter (WM) lesions are closely associated with cognitive impairment and gait disorders in the elderly. We have successfully established a mouse model of chronic cerebral hypoperfusion that may … Cerebrovascular white matter (WM) lesions are closely associated with cognitive impairment and gait disorders in the elderly. We have successfully established a mouse model of chronic cerebral hypoperfusion that may provide new strategies for the molecular analysis of cerebrovascular WM lesions.Adult C57Bl/6 male mice were subjected to bilateral common carotid artery stenosis (BCAS) using external microcoils with varying inner diameters from 0.16 to 0.22 mm. Cerebral blood flow (CBF) in the frontal cortices was measured by laser-Doppler flowmetry at 2 hours and at 1, 3, 7, 14, and 30 days after BCAS. The brains were then removed and examined at 30 days with histological stains and immunohistochemistry for markers of microglia and astroglia.At 2 hours, the CBF values (ratio to the preoperative value) did not change in the 0.22 mm group but decreased significantly to 77.3+/-13.4% in the 0.20 mm group, 67.3+/-18.5% in the 0.18 mm group, and 51.4+/-11.5% in the 0.16 mm group. At day 1, the CBF began to recover in all groups but remained significantly lower until 14 days in comparison to the control group. In the 0.20 mm and 0.18 mm groups, WM lesions occurred after 14 days without any gray matter involvement. These lesions were the most intense in the corpus callosum adjacent to the lateral ventricle but were mild in the anterior commissure and optic tract. In contrast, 4 of 5 mice developed some gray matter changes in the 0.16 mm group. The proliferation of activated microglia and astroglia was observed in the WM beyond 3 days after BCAS.WM lesions were successfully induced after chronic cerebral hypoperfusion with relative preservation of the visual pathway. These features in this mouse model are appropriate for cognitive assessment and genetic analysis, and it may provide a powerful tool to understand the pathophysiology of WM lesions.
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Brain Atrophy in Type 2 Diabetes

2013-08-13
Chris Moran , Thanh G. Phan , Jian Chen +7 more
Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or … Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function.This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures.T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume.Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.
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Cerebral White Matter Lesions and the Risk of Dementia

2004-10-01
Niels D. Prins , Ewoud J. van Dijk , Tom den Heijer +5 more
<h3>Objective</h3> To study the association between white matter lesions (WML) in specific locations and the risk of dementia. <h3>Design</h3> The Rotterdam Scan Study, a prospective population-based cohort study. We scored … <h3>Objective</h3> To study the association between white matter lesions (WML) in specific locations and the risk of dementia. <h3>Design</h3> The Rotterdam Scan Study, a prospective population-based cohort study. We scored periventricular and subcortical WML on magnetic resonance imaging and observed participants until January 2002 for incident dementia. <h3>Setting</h3> General population. <h3>Participants</h3> We included 1077 people aged 60 to 90 years who did not have dementia at baseline. <h3>Main Outcome Measure</h3> Incident dementia by<i>Diagnostic and Statistical Manual of Mental Disorders, Third Edition</i>(<i>DSM III-R</i>) criteria. <h3>Results</h3> During a mean follow-up of 5.2 years, 45 participants developed dementia. Higher severity of periventricular WML increased the risk of dementia, whereas the association between subcortical WML and dementia was less prominent. The adjusted hazard ratio of dementia for each standard deviation increase in periventricular WML severity was 1.67 (95% confidence interval, 1.25-2.24). This increased risk was independent of other risk factors for dementia and partly independent of other structural brain changes on magnetic resonance imaging. <h3>Conclusion</h3> White matter lesions, especially in the periventricular region, increase the risk of dementia in elderly people.

Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases

2007-01-19
Eszter Farkas , Paul G.M. Luiten , Ferenc Bari
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A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction.

1986-07-01
S T Chen , Chung Y. Hsu , E. L. Hogan +2 more
In the search for a more reproducible focal ischemic stroke model in the rat, we systematically interrupted blood flow to the right middle cerebral artery territory by ligating the right … In the search for a more reproducible focal ischemic stroke model in the rat, we systematically interrupted blood flow to the right middle cerebral artery territory by ligating the right middle cerebral artery, and the right and left common carotid arteries in succession. Using a laser-Doppler flowmeter, we found that the relative surface blood flow in cerebral cortex supplied by the right middle cerebral artery decreased to 62, 48, and 18% of baseline respectively after successive ligation of the right middle cerebral artery, and the right and left common carotid arteries. A focal infarct in the cerebral cortex supplied by the right middle cerebral artery was consistently noted after ligation of the right middle cerebral and the right common carotid arteries and temporary clip occlusion of the left common carotid artery for 60 min. The surface areas of infarction measured 100 +/- 6 mm2 and the maximal cross-sectional area of infarction was 10.4 +/- 1.1 mm2 (N = 10). The mortality rate was 7% (N = 70). The characteristic changes of ischemic necrosis were limited to the cortex with sparing of subcortical structures. No motor deficits occurred. Occlusion of the right middle cerebral artery alone or together with the right common carotid artery did not consistently cause gross infarction and the maximal cross-sectional area of infarction was smaller (the right middle cerebral artery, 1.7 +/- 0.8 mm2, N = 10; the right middle cerebral artery plus the right common carotid artery, 4.8 +/- 1.9 mm2, N = 10). Permanent ligation of the right middle cerebral artery and both common carotid arteries had a high mortality (60% in 3 days, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
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Blood brain barrier: ageing and microvascular disease-systematic review and meta-analysis

2009-07-17
Andrew Farrall , Joanna M. Wardlaw

Cerebral hypoperfusion and clinical onset of dementia: The Rotterdam study

2005-05-31
Annemieke Ruitenberg , Tom den Heijer , S. L. M. Bakker +4 more
Abstract Cerebral blood flow (CBF) velocity is decreased in patients with Alzheimer's disease. It is being debated whether this reflects diminished demand because of advanced neurodegeneration or that cerebral hypoperfusion … Abstract Cerebral blood flow (CBF) velocity is decreased in patients with Alzheimer's disease. It is being debated whether this reflects diminished demand because of advanced neurodegeneration or that cerebral hypoperfusion contributes to dementia. We examined the relation of CBF velocity as measured with transcranial Doppler with dementia and markers of incipient dementia (ie, cognitive decline and hippocampal and amygdalar atrophy on magnetic resonance imaging) in 1,730 participants of the Rotterdam Study aged 55 years and older. Cognitive decline in the 6.5 years preceding CBF velocity measurement was assessed with repeated Mini‐Mental State Examinations in nondemented subjects (n = 1,716). Hippocampal and amygdalar volumes were assessed in a subset of 170 nondemented subjects. Subjects with greater CBF velocity were less likely to have dementia. Furthermore, in nondemented subjects, greater CBF velocity was related to significantly less cognitive decline over the preceding period (odds ratio per standard deviation increase in mean CBF 0.74 [95% confidence interval, 0.58–0.98]) and larger hippocampal and amygdalar volumes. A low CBF is associated with dementia, but also with markers of incipient dementia. Although we cannot exclude that this is caused by preclinical neurodegeneration leading to hypoperfusion, it does suggest that cerebral hypoperfusion precedes and possibly contributes to onset of clinical dementia. Ann Neurol 2005;57:789–794

The neuroprotective potential of flavonoids: a multiplicity of effects

2008-10-20
David Vauzour , Katerina Vafeiadou , Ana Rodriguez‐Mateos +2 more

Alzheimer Disease as a Vascular Disorder

2002-04-01
J. C. de la Torre
The main stumbling block in the clinical management and in the search for a cure of Alzheimer disease (AD) is that the cause of this disorder has remained uncertain until … The main stumbling block in the clinical management and in the search for a cure of Alzheimer disease (AD) is that the cause of this disorder has remained uncertain until now.Evidence that sporadic (nongenetic) AD is primarily a vascular rather than a neurodegenerative disorder is reviewed. This conclusion is based on the following evidence: (1) epidemiological studies showing that practically all risk factors for AD reported thus far have a vascular component that reduces cerebral perfusion; (2) risk factor association between AD and vascular dementia (VaD); (3) improvement of cerebral perfusion obtained from most pharmacotherapy used to reduce the symptoms or progression of AD; (4) detection of regional cerebral hypoperfusion with the use of neuroimaging techniques to preclinically identify AD candidates; (5) presence of regional brain microvascular abnormalities before cognitive and neurodegenerative changes; (6) common overlap of clinical AD and VaD cognitive symptoms; (7) similarity of cerebrovascular lesions present in most AD and VaD patients; (8) presence of cerebral hypoperfusion preceding hypometabolism, cognitive decline, and neurodegeneration in AD; and (9) confirmation of the heterogeneous and multifactorial nature of AD, likely resulting from the diverse presence of vascular risk factors or indicators of vascular disease.Since the value of scientific evidence generally revolves around probability and chance, it is concluded that the data presented here pose a powerful argument in support of the proposal that AD should be classified as a vascular disorder. According to elementary statistics, the probability or chance that all these findings are due to an indirect pathological effect or to coincidental circumstances related to the disease process of AD seems highly unlikely. The collective data presented in this review strongly support the concept that sporadic AD is a vascular disorder. It is recommended that current clinical management of patients, treatment targets, research designs, and disease prevention efforts need to be critically reassessed and placed in perspective in light of these important findings.
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Increased intrathecal levels of the angiogenic factors VEGF and TGF-β in Alzheimer’s disease and vascular dementia

2002-03-01
E. Tarkowski , Razao Issa , Magnus Sjögren +4 more

Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease

2015-12-18
Amy R. Nelson , Melanie D. Sweeney , Abhay P. Sagare +1 more
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Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions.

1994-03-01
Toshiaki Watanabe , Satoshi Yuki , Mariko Egawa +1 more
The anti-ischemic effects and a possible mechanism of a new antistroke agent, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied. Preischemic treatment with MCI-186 (3 mg/kg i.v.) facilitated the recovery of electrocorticographic activity and … The anti-ischemic effects and a possible mechanism of a new antistroke agent, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied. Preischemic treatment with MCI-186 (3 mg/kg i.v.) facilitated the recovery of electrocorticographic activity and prolonged survival time in global complete ischemia of rats; MCI-186 (1 and 3 mg/kg i.v.) also mitigated dysfunction of the blood-brain barrier and energy failure in hemispheric embolization of rats. Postischemic treatment with MCI-186 (3 mg/kg i.v.) decreased cortical infarction in focal embolization of rats. MCI-186 (0.6-2.4 mM) inhibited the OH.-induced hydroxylation of salicylate (maximal inhibition, 40.2%), but at 100 microM it did not influence O2- generation. MCI-186 inhibited the formation of linoleic acid-conjugated dienes caused by OH. (IC50 = 32.0 microM). Also, concurrent administration of MCI-186 (3-100 mg/kg i.v.) ameliorated hyperglycemia, hyperlipopeoxidemia and degranulation of beta-cells in alloxan (40 mg/kg i.v.)-treated rats. In addition, MCI-186 inhibited iron-dependent peroxidation in rat brain homogenates and mitochondrial homogenates (IC50 = 15.0 and 2.3 microM, respectively) and prevented iron-dependent peroxidative disintegration of mitochondrial membranes (IC50 = 39.0 microM). These findings suggest that MCI-186 has potent anti-ischemic actions and that its mechanism may be closely associated with beneficial antioxidant activities.

Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease

2016-05-06
Subbiah Pugazhenthi , Limei Qin , P. Hemachandra Reddy
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Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease

2016-06-27
Mak Adam Daulatzai
Aging, hypertension, diabetes, hypoxia/obstructive sleep apnea (OSA), obesity, vitamin B12/folate deficiency, depression, and traumatic brain injury synergistically promote diverse pathological mechanisms including cerebral hypoperfusion and glucose hypometabolism. These risk factors … Aging, hypertension, diabetes, hypoxia/obstructive sleep apnea (OSA), obesity, vitamin B12/folate deficiency, depression, and traumatic brain injury synergistically promote diverse pathological mechanisms including cerebral hypoperfusion and glucose hypometabolism. These risk factors trigger neuroinflammation and oxidative‐nitrosative stress that in turn decrease nitric oxide and enhance endothelin, Amyloid‐β deposition, cerebral amyloid angiopathy, and blood–brain barrier disruption. Proinflammatory cytokines, endothelin‐1, and oxidative‐nitrosative stress trigger several pathological feedforward and feedback loops. These upstream factors persist in the brain for decades, upregulating amyloid and tau, before the cognitive decline. These cascades lead to neuronal Ca 2+ increase, neurodegeneration, cognitive/memory decline, and Alzheimer's disease (AD). However, strategies are available to attenuate cerebral hypoperfusion and glucose hypometabolism and ameliorate cognitive decline. AD is the leading cause of dementia among the elderly. There is significant evidence that pathways involving inflammation and oxidative‐nitrosative stress (ONS) play a key pathophysiological role in promoting cognitive dysfunction. Aging and several comorbid conditions mentioned above promote diverse pathologies. These include inflammation, ONS, hypoperfusion, and hypometabolism in the brain. In AD, chronic cerebral hypoperfusion and glucose hypometabolism precede decades before the cognitive decline. These comorbid disease conditions may share and synergistically activate these pathophysiological pathways. Inflammation upregulates cerebrovascular pathology through proinflammatory cytokines, endothelin‐1, and nitric oxide (NO). Inflammation‐triggered ONS promotes long‐term damage involving fatty acids, proteins, DNA, and mitochondria; these amplify and perpetuate several feedforward and feedback pathological loops. The latter includes dysfunctional energy metabolism (compromised mitochondrial ATP production), amyloid‐β generation, endothelial dysfunction, and blood–brain‐barrier disruption. These lead to decreased cerebral blood flow and chronic cerebral hypoperfusion‐ that would modulate metabolic dysfunction and neurodegeneration. In essence, hypoperfusion deprives the brain from its two paramount trophic substances, viz., oxygen and nutrients. Consequently, the brain suffers from synaptic dysfunction and neuronal degeneration/loss, leading to both gray and white matter atrophy, cognitive dysfunction, and AD. This Review underscores the importance of treating the above‐mentioned comorbid disease conditions to attenuate inflammation and ONS and ameliorate decreased cerebral blood flow and hypometabolism. Additionally, several strategies are described here to control chronic hypoperfusion of the brain and enhance cognition. © 2016 Wiley Periodicals, Inc.
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Diabetes and Cognitive Impairment

2016-08-04
Lindsay Zilliox , Krish Chadrasekaran , Justin Kwan +1 more

Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area.

1997-04-01
J. M. Orgogozo , J.F. Dartigues , Sylviane Lafont +5 more

Impaired neurovascular coupling in aging and Alzheimer's disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline

2016-11-11
Stefano Tarantini , Cam Ha T. Tran , Grant R. Gordon +2 more
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Free Radical Damage in Ischemia‐Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy

2018-01-01
Ming-Shuo Sun , Hang Jin , Xin Sun +4 more
Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. … Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury after revascularization therapy can result in worsening outcomes. Among all possible pathological mechanisms of ischemia-reperfusion injury, free radical damage (mainly oxidative/nitrosative stress injury) has been found to play a key role in the process. Free radicals lead to protein dysfunction, DNA damage, and lipid peroxidation, resulting in cell death. Additionally, free radical damage has a strong connection with inducing hemorrhagic transformation and cerebral edema, which are the major complications of revascularization therapy, and mainly influencing neurological outcomes due to the disruption of the blood-brain barrier. In order to get a better clinical prognosis, more and more studies focus on the pharmaceutical and nonpharmaceutical neuroprotective therapies against free radical damage. This review discusses the pathological mechanisms of free radicals in ischemia-reperfusion injury and adjunctive neuroprotective therapies combined with revascularization therapy against free radical damage.
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Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications

2018-07-18
Geert Jan Biessels , Florin Despa
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Current advances in ischemic stroke research and therapies

2018-09-16
Derek Barthels , Hiranmoy Das

Inflammation and cerebral small vessel disease: A systematic review

2019-06-10
Audrey Low , Elijah Mak , James B. Rowe +2 more

Vascular Cognitive Impairment and Dementia

2019-06-24
Costantino Iadecola , Marco Duering , Vladimir Hachinski +4 more
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Hypertension-induced cognitive impairment: from pathophysiology to public health

2021-06-14
Zoltán Ungvári , Péter Tóth , Stefano Tarantini +4 more

Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study

1996-03-25
S. O. Keli

The role of a mammalian network in regulating ischemic stroke outcome

2025-09-05
Giudice Luca Scoyni Flavia
QUICK GUIDE ABOUT THE FOLDERS AND FILES This repository contains the code used to align the sequences and to analyse the counts used in the paper: The role of a … QUICK GUIDE ABOUT THE FOLDERS AND FILES This repository contains the code used to align the sequences and to analyse the counts used in the paper: The role of a mammalian network in regulating ischemic stroke outcome. Plus, it has intermediary files regarding steps of data processing. For example, the output files produced with fastqc, multiqc, PCA and other methods. The raw fastq files of the aligned sequences can be downloaded from GEO database using the links provided in the publication. "Alignments" folder contains the code used to align and quantify the sequencing data. Each subfolder is associated to a specific sequencing dataset used in the paper.For miRNA and total RNA sequences, we used the corresponding nf-core pipeline.For circular sequences, we used ciriquant software pulled into a local docker.For each run of nf-core pipeline and ciriquant, we kept the most important intermediary files like the ones related to quality control from "fastqc" and "multiqc".For each run of nf-core pipeline, the subfolder "pipeline_info" contains the report of the execution of the nf-core pipeline and the command used to call it.For ciriquant run, config.yml and op0_CIRIquant.sh show which has been the setting and files used for the execution.The alignment of total RNA sequencing data has been performed twice.Standard alignment with default parameters.Edited_genome alignment with the mm10 genome annotation modified to include Cdr1as.Mus_musculus folder contains the mm10 genome annotation modified to include Cdr1as. "Analysis" folder contains the code to analyse the counts produced with the nf-core and ciriquant pipelines.Each subfolder is associated to a specific sequencing dataset used in the paper.The scripts of a folder are always indipendent from the files belonging to other folders.The scripts are ordered based on how they must be executed, so op1, op2, op3 ...The scripts always elaborate the data coming from their "data" folder, use the functions inside their own "funs" folder and produce the results in their own "output" folder; changing the structure of a folder may give errors during the execution of a script. "Analysis_revision" folder contains the code to add to the "Analysis" folder.This code has been added to reply to reviewer's comments. BE CAREFULL: both the code for the alignments and analysis includes pointers to file paths which must be changed in order to be run in your system.

The role of a mammalian network in regulating ischemic stroke outcome

2025-09-05
Giudice Luca Scoyni Flavia
QUICK GUIDE ABOUT THE FOLDERS AND FILES This repository contains the code used to align the sequences and to analyse the counts used in the paper: The role of a … QUICK GUIDE ABOUT THE FOLDERS AND FILES This repository contains the code used to align the sequences and to analyse the counts used in the paper: The role of a mammalian network in regulating ischemic stroke outcome. Plus, it has intermediary files regarding steps of data processing. For example, the output files produced with fastqc, multiqc, PCA and other methods. The raw fastq files of the aligned sequences can be downloaded from GEO database using the links provided in the publication. "Alignments" folder contains the code used to align and quantify the sequencing data. Each subfolder is associated to a specific sequencing dataset used in the paper.For miRNA and total RNA sequences, we used the corresponding nf-core pipeline.For circular sequences, we used ciriquant software pulled into a local docker.For each run of nf-core pipeline and ciriquant, we kept the most important intermediary files like the ones related to quality control from "fastqc" and "multiqc".For each run of nf-core pipeline, the subfolder "pipeline_info" contains the report of the execution of the nf-core pipeline and the command used to call it.For ciriquant run, config.yml and op0_CIRIquant.sh show which has been the setting and files used for the execution.The alignment of total RNA sequencing data has been performed twice.Standard alignment with default parameters.Edited_genome alignment with the mm10 genome annotation modified to include Cdr1as.Mus_musculus folder contains the mm10 genome annotation modified to include Cdr1as. "Analysis" folder contains the code to analyse the counts produced with the nf-core and ciriquant pipelines.Each subfolder is associated to a specific sequencing dataset used in the paper.The scripts of a folder are always indipendent from the files belonging to other folders.The scripts are ordered based on how they must be executed, so op1, op2, op3 ...The scripts always elaborate the data coming from their "data" folder, use the functions inside their own "funs" folder and produce the results in their own "output" folder; changing the structure of a folder may give errors during the execution of a script. "Analysis_revision" folder contains the code to add to the "Analysis" folder.This code has been added to reply to reviewer's comments. BE CAREFULL: both the code for the alignments and analysis includes pointers to file paths which must be changed in order to be run in your system.

Statement of Retraction: Ephedrine alleviates middle cerebral artery occlusion-induced neurological deficits and hippocampal neuronal damage in rats by activating PI3K/AKT signaling pathway

2025-06-25
| Bioengineered

Causes and consequences of vascular dementia across the life course: Evidence from a UK Biobank phenome-wide and Mendelian randomization study

2025-06-23
Phazha LK Bothongo , Victoria Taylor‐Bateman , Roxanna Korologou‐Linden +5 more
Abstract Background Vascular dementia (VaD) is the second most common cause of dementia, yet its risk factors and biological mechanisms remain poorly understood. Objective To identify causes and consequences of … Abstract Background Vascular dementia (VaD) is the second most common cause of dementia, yet its risk factors and biological mechanisms remain poorly understood. Objective To identify causes and consequences of VaD by developing a polygenic risk score (PRS) for VaD and conducting a phenome-wide association study (PheWAS), followed by Mendelian randomization (MR) analyses using data from the UK Biobank. Methods Using data from 334,758 UK Biobank participants, we first constructed a VaD PRS based on the most recent genome-wide association study (GWAS). We then performed an age-stratified PheWAS (39–53, 53–62, 62–72 years), examining 9,319 phenotypes associated with the VaD PRS. We followed up PheWAS hits with two-sample MR to evaluate causal relationships with VaD risk. Results Our PheWAS revealed age-dependent associations, with many relationships strengthening as age increased. Associations were found with vascular and Alzheimer’s dementias; cerebrovascular traits such as white matter hyperintensities (WMH), stroke, and intracerebral haemorrhage; adverse lipid profiles; elevated systolic blood pressure and glucose levels; reduced brain volumes (subcortical and hippocampal); and poorer cognitive function. The VaD PRS was also associated with higher risk of depression, Parkinson’s disease, neuroinflammatory disorders, and decreased basal metabolic rate and fat-free mass. MR analyses supported causal effects for WMH (OR: 1.83, 95% CI: 1.39–2.40), depression (1.25, 1.02–1.54), lipid traits (e.g., apolipoprotein B/A1 ratio: 1.31, 1.06–1.62), HbA1c (1.14, 1.02–1.28), and diastolic (1.03, 1.01–1.04) and systolic (1.01, 1.01–1.02) blood pressure. Protective factors included years of schooling (0.76, 0.64–0.90), apolipoprotein A (0.74, 0.59–0.92), fat-free mass (0.84, 0.71–0.99), and basal metabolic rate (0.82, 0.69–0.97). Conclusions Our findings highlight the central role of cardiometabolic and educational factors in the development of vascular dementia. Several modifiable risk factors—particularly blood pressure, glucose regulation, lipid levels, and years of schooling—showed evidence of causal effects on VaD risk. Age-stratified results suggest that early intervention, ideally from midlife, may offer the greatest preventive benefit by mitigating the progressive accumulation of vascular damage contributing to dementia risk.

Exploring research trends and hotspots in PI3K/Akt signaling pathway in ischemic stroke: a bibliometric analysis

2025-06-23
Yingquan Liu , Yu Ye , Lin Bai +4 more | Frontiers in Molecular Neuroscience
Objective This study explores potential therapeutic strategies by determining the current research status, hotspots, and development trends through bibliometric analysis of the PI3K/Akt in ischemic stroke (IS). Methods We searched … Objective This study explores potential therapeutic strategies by determining the current research status, hotspots, and development trends through bibliometric analysis of the PI3K/Akt in ischemic stroke (IS). Methods We searched the Web of Science Core Collection for publications on IS and the PI3K/Akt pathway, covering January 1, 2010, to December 31, 2024. VOSviewer and CiteSpace software were used to analyze research hotspots and cutting-edge topics in the field and generate visual maps of relevant countries, institutions, authors, journals, keywords, and references. Results A total of 635 publications were analyzed. The number of publications indicates a steady annual increase in research output. China, Capital Medical University, and Wang Lei were identified as the most prolific country, institution, and author, respectively. The top three contributing journals were Brain Research , Journal of Ethnopharmacology , and Frontiers in Pharmacology . Autophagy, microglia and neuroinflammation, bioinformatics approaches, and traditional Chinese medicine (TCM) are not only current research areas but also important trends for future research. Notably, targeting IS with TCM holds significant potential for translating basic research findings into clinical applications. Conclusion This bibliometric analysis provides an in-depth overview of research on the PI3K/Akt pathway in IS, revealing current research status, hotspots, and future research trends. This will provide valuable guidance and direction for developing novel therapeutic strategies targeting this pathway.

Multi-Target Protective Effects of β-Caryophyllene (BCP) at the Intersection of Neuroinflammation and Neurodegeneration

2025-06-23
Caterina Ricardi , Anna Mazzierli , Stefano Guglielmo +5 more | International Journal of Molecular Sciences
Recent advances in cannabinoid-based therapies identified the natural CB2 receptor agonist β-caryophyllene (BCP) as a promising anti-inflammatory and neuroprotective agent. To further explore its therapeutic potential on the management of … Recent advances in cannabinoid-based therapies identified the natural CB2 receptor agonist β-caryophyllene (BCP) as a promising anti-inflammatory and neuroprotective agent. To further explore its therapeutic potential on the management of neurodegenerative disorders, in the present study we investigated the ability of BCP to prevent neuroinflammation and promote neuroprotection by using both in vitro and ex vivo models of β-amyloid induced neurotoxicity. Our data showed that BCP significantly protected human microglial HMC3 cells from Aβ25-35-induced cytotoxicity, reducing the release of pro-inflammatory cytokines (TNF-α, IL-6) while enhancing IL-10 secretion. These effects were associated with a reduced activation of the NF-κB pathway, which emerged as a central mediator of BCP action. Notably, the use of CB2R- or PPARγ-selective antagonists revealed that the observed NF-κB inhibition by BCP may involve the coordinated activation of both canonical (e.g., CB2R) and non-canonical (e.g., PPARγ) receptors. Moreover, BCP restored the expression of SIRT1, PGC-1α, and BDNF, indicating the involvement of neurotrophic pathways. Clear neuroprotective properties for BCP have been highlighted in Aβ1-42-treated brain slice preparations, where BCP demonstrated the rescue of both the amyloid-dependent depression of BDNF expression and long-term synaptic potentiation (LTP) impairment. Overall, our results suggest that BCP constitutes an attractive natural molecule for the treatment of Aβ-induced neuroinflammation and synaptic dysfunction, warranting further exploration for its clinical application.

Qishentaohong Granules Alleviate Heart Failure by Modulating Mitochondrial Fission and Mitophagy Balance

2025-06-21
Jialin Jin , Yuxuan Li , Xiang Li +7 more | Journal of Ethnopharmacology

Corrigendum to “JLX001 Ameliorates ischemia/reperfusion injury by reducing neuronal apoptosis via downregulating JNK signaling pathway” [Neuroscience 418 (2019) 189–204]

2025-06-21
Lin Zhou , Luyao Ao , Yunyi Yan +7 more | Neuroscience

How Much Do Vascular Risk Factors Contribute to Dementia?

2025-06-20
Samantha Anderer | JAMA

EGb761 suppressed vascular dementia via modulating Wnt/β-catenin signaling pathway-induced apoptosis and autophagy in hippocampal neuronal cells

2025-06-19
Nan Yin , Zhipeng Tang , Yanyan Yang +4 more | European journal of medical research

[Identifying genetic etiology of ischemic stroke based on pleiotropy of obesity related genes: A sibling study].

2025-06-18
Kai Wang , Huijun Wang , Hao Yu +7 more | PubMed
To identify genetic etiology of ischemic stroke (IS) based on pleiotropy of obesity related genes. A discordant sib-pair study was designed based on the Fangshan family cohort in Beijing. Body … To identify genetic etiology of ischemic stroke (IS) based on pleiotropy of obesity related genes. A discordant sib-pair study was designed based on the Fangshan family cohort in Beijing. Body mass index (BMI) polygenic risk score (PRS) was first constructed under different P values. Using the polygenic transmission disequilibrium test (pTDT), we then compared the actual BMI genetic risk of siblings with IS to their expected risk, to analyze whether higher BMI was over-transmitted to siblings with IS. The single nucleotide polymorphism (SNP) that comprised the PRS over-transmitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS. This set was then utilized as a candidate set to identify and verify risk SNPs asso-ciated IS by transmission disequilibrium test. Finally, we identified independent genomic risk loci and mapped to genes, we then explored the biological function of the identified risk loci and genes by functional annotation and pathway enrichment. A total of 541 participants were enrolled, with an average age of (58.4±8.1) years, including 326 discordant sib pairs of ischemic stroke. Compared with non-IS participants, IS participants with males, education level below junior high school, hypertension and hyperlipidemia accounted for a higher proportion (P < 0.05). For all the BMI PRS, we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation, suggesting that genetic risk associated with high BMI was over-transmitted with IS. Compared with other SNP sets, the set (P < 5×10-4) corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS. Within this set, there were 45 SNPs having linkage and association with IS, which were located in 43 independent genomic risk loci and mapped to 40 genes. These genes were significantly enriched in the lipid metabolism pathway. The rs2232852 corrected by multiple tests was mapped to CYB5R1 and ADIPOR1, which were related to lipid metabolism and the ferroptosis pathway. Pleiotropy between BMI-related genes and IS was observed. Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes, which were functionally enriched in lipid metabolic pathways. The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1, which were related to lipid metabolism and the ferroptosis pathway, suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Therapeutic potential of natural products in ischemic stroke: targeting angiogenesis

2025-06-18
Wenyuan Li , E Liu , Yihao Zhou +2 more | Frontiers in Pharmacology
Ischemic stroke (IS), a leading global cause of mortality and long-term disability, necessitates immediate intervention for eligible patients. Current guidelines mandate intravenous thrombolysis within 4.5 h of symptom onset for … Ischemic stroke (IS), a leading global cause of mortality and long-term disability, necessitates immediate intervention for eligible patients. Current guidelines mandate intravenous thrombolysis within 4.5 h of symptom onset for individuals without contraindications, achieving vessel recanalization rates up to 85% in treated cohorts. However, therapeutic time windows may extend to 4.5–24 h for select patients when guided by advanced multimodal imaging (CT perfusion or diffusion-weighted MRI) to identify salvageable penumbral tissue. While revascularization remains the cornerstone of acute IS management, emerging evidence underscores angiogenesis as a critical biological process for neurovascular repair and functional recovery during the subacute-to-chronic phases. Natural products (NPs), have demonstrated multiple advantages in the treatment of IS, including multi-target modulation, relatively easy access to raw materials, relatively low price, and the significant advantage of having wide selectivity offer novel opportunities for addressing these limitations. This review systematically analyses 13 major NPs classes including saponins, terpenoids, cycloenol ether terpene glycosides, flavonoids, ketones and macrocycles, phenolic acids, phenylpropanoids, polysaccharides, phenolphthaleins, complexes/extracts, volatile oils, alkaloids, and polymeric materials complexes class of compounds, We elucidate the molecular cascade in which NPs regulate the hypoxia-inducible factor 1α (HIF-1α)/Vascular endothelial growth factor (VEGF), Notch and Wnt/β-catenin signaling pathways to promote vascular regeneration. In particular, our study focuses on the critical role of angiogenesis during the development of IS, highlighting that NPs can enhance neovascularization by alleviating oxidative stress/inflammation, among other pathways. These insights offer translational possibilities for the development of NP-based combination therapies targeting both the acute neuroprotective and chronic recovery phases.

Retraction Note to: Anthocyanins Improve Hippocampus-Dependent Memory Function and Prevent Neurodegeneration via JNK/Akt/GSK3β Signaling in LPS-Treated Adult Mice

2025-06-17
Muhammad Sohail Khan , Tahir Ali , Min Woo Kim +3 more | Molecular Neurobiology

Lycium barbarum polysaccharide alleviates neurobehavioral deficits in mice with ischemic cerebral injury

2025-06-16
Ruiqing Mian , Liqiong Ma | bioRxiv (Cold Spring Harbor Laboratory)
Objective: To investigate the effects of Lycium barbarum polysaccharides (LBP) on neurobehavioral impairments in mice with ischemic stroke and explore the underlying mechanisms. Methods: A middle cerebral artery occlusion (MCAO) … Objective: To investigate the effects of Lycium barbarum polysaccharides (LBP) on neurobehavioral impairments in mice with ischemic stroke and explore the underlying mechanisms. Methods: A middle cerebral artery occlusion (MCAO) model was established using the filament occlusion method to evaluate the therapeutic effects of LBP on pathological brain tissue damage after cerebral ischemia-reperfusion injury (I/R). Mice were randomly divided into three groups: sham surgery (Sham), I/R, and I/R + LBP. Behavioral tests, including the Y-maze test, rotarod test, and balance beam test, were systematically conducted to assess the impact of LBP on neurobehavioral impairments. Enzyme-linked immunosorbent assay (ELISA) was used to quantify peripheral blood levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), reflecting inflammatory status. Results: LBP significantly ameliorated neuroinflammation and oxidative stress in mice with cerebral I/R injury, demonstrating marked protection against I/R-induced neurofunctional damage. LBP notably improved motor and memory deficits caused by ischemic stroke. Compared to the I/R group, LBP improved neuroinflammation and oxidative stress levels post-I/R injury. Conclusion: This study demonstrates that LBP alleviates ischemic stroke-induced neurological damage by attenuating inflammatory responses.

G protein and MYD Growth Factor in neuroprotection after cerebral ischemia-reperfusion

2025-06-15
Yisheng Cheng , Xiaoxiao Cheng , Han Zhao +1 more | Neurological Research
To explore the neuroprotective role of Myeloid-Derived Growth Factor (MYDGF) and its regulatory mechanisms involving G protein-coupled signaling pathways after cerebral ischemia-reperfusion injury (CIRI). A mouse model of CIRI was … To explore the neuroprotective role of Myeloid-Derived Growth Factor (MYDGF) and its regulatory mechanisms involving G protein-coupled signaling pathways after cerebral ischemia-reperfusion injury (CIRI). A mouse model of CIRI was established using middle cerebral artery occlusion (MCAO). Mice were divided into five groups: Mock, scramble shRNA (sh-scr), MYDGF knockdown (MYDGF-shRNA), Gαi1/3 knockdown (Gαi1/3-shRNA), and recombinant MYDGF treatment. MYDGF mRNA expression was analyzed using qRT-PCR, and protein levels were assessed via Western blot. Cell-type specific knockdown in glial cells was achieved using targeted adenoviral shRNA. MYDGF exerted neuroprotective effects by activating PI3K-AKT-mTOR and ERK-MAPK signaling pathways. Gαi1/3 was identified as a key regulatory factor mediating these effects. MYDGF exerted neuroprotective effects by activating PI3K-AKT-mTOR and ERK-MAPK signaling pathways. Gαi1/3 was identified as a key regulatory factor mediating these effects.

22-OR: Type 2 Diabetes Subtypes and Risk of Dementia in the United States

2025-06-13
Zhongyu Li , Bertha Cecilia Salazar , Jiali Guo +5 more | Diabetes
Introduction and Objective: Dementia, an emerging complication of type 2 diabetes (T2D), may be driven by chronic hyperglycemia and insulin resistance. We evaluated the risk of dementia across T2D subtypes, … Introduction and Objective: Dementia, an emerging complication of type 2 diabetes (T2D), may be driven by chronic hyperglycemia and insulin resistance. We evaluated the risk of dementia across T2D subtypes, which differ in clinical profiles and risk of vascular complications. Methods: We identified newly diagnosed T2D (n = 727,076; age: 64.4 years [SD:13.3], 52% female) over 2012-2023 from the Epic Cosmos platform and classified them into Severe Insulin-Deficient Diabetes (SIDD, 21.6%), Mild Obesity-Related Diabetes (MOD, 23.8%), Mild Age-Related Diabetes (MARD, 40.9%) or Unclassified (i.e., Mixed; 13.7%). First occurrence of any dementia and also specific risks of vascular dementia, Alzheimer’s, and other dementias within ten years after T2D diagnosis were identified using ICD-10-CM codes. Cox proportional hazards models were used to estimate covariate-adjusted absolute and relative hazards (HR) by subtype. Results: Compared with MOD, SIDD (HR: 2.25 [95%CI: 1.92, 2.64]) and MARD (2.00 [1.70, 2.34]) had higher hazards for any dementia (Figure). Unclassified diabetes showed intermediate hazards of any dementia (1.38 [1.16, 1.65]). Risks of vascular, Alzheimer’s, and other dementias were also higher in SIDD and MARD compared to MOD and Unclassified diabetes. Conclusion: T2D subtypes differ in dementia risks, emphasizing the need for research into tailored prevention strategies and early screening, particularly for SIDD and MARD. Disclosure Z. Li: None. B. Salazar: None. J. Guo: None. K.O. Sanaka: None. A. Kahkoska: None. P. Vellanki: Advisory Panel; Eli Lilly and Company. M.K. Ali: Advisory Panel; Eli Lilly and Company. J. Varghese: None.

Betaine protects cerebral microvascular endothelium and ameliorates hypertension-induced cognitive dysfunction via upregulation of the endothelial nitric oxide synthase/nitric monoxide signaling pathway

2025-06-13
Jiale Sun , Wei Zhang , Xueying Wang +2 more | Journal of Hypertension
Objectives: Hypertension-induced endothelial damage in cerebral microvessels is a key factor contributing to vascular cognitive impairment (VCI). Endothelial function stabilization considerably depends on the endothelial nitric oxide synthase (eNOS)/nitrogen monoxide … Objectives: Hypertension-induced endothelial damage in cerebral microvessels is a key factor contributing to vascular cognitive impairment (VCI). Endothelial function stabilization considerably depends on the endothelial nitric oxide synthase (eNOS)/nitrogen monoxide (NO) pathway. Furthermore, the eNOS/NO signaling pathway plays a role in stabilizing the vascular endothelium. Although betaine (bet) has been shown to improve cognitive dysfunction, its underlying mechanisms remain unclear. Therefore, this study aimed to determine whether betaine protects cognitive function by regulating eNOS/NO activity. Methods: Male 7-month-old spontaneously hypertensive rats (SHR) were randomly assigned to four groups: SHR, Bet, Bet and N(G)-Nitroarginine methyl ester hydrochloride (L-NAME), and L-NAME groups. Male 7-month-old Wistar Kyoto rats (WKY) served as controls. All animals received treatment or saline for 4 weeks. In-vitro experiments were conducted using rat brain microvascular endothelial cells (RBMECs) treated with either homocysteine (Hcy) or betaine. Behavioral experiments, western blotting, pathological tissue staining, Doppler ultrasound technique, and ELISA were employed to assess the impact of hypertension on cognitive and endothelial functions. Results: Hypertension led to cognitive decline in SHR by causing endothelial dysfunction, blood-brain barrier disruption, inflammation, oxidative stress, and apoptosis. Bet administration significantly improved these pathological indicators of cognitive impairment; however, the eNOS inhibitor L-NAME reversed its effects. Conclusion: Our findings suggest that betaine protects vascular endothelium and improves VCI by modulating the eNOS/NO signaling pathway.

Long intervals between repetitive concussions reduce risk of cognitive impairment and limit microglial activation, astrogliosis, and tauopathy in adolescent rats

2025-06-12
Yuichi Hirata , Kyohei Kin , Takayuki Nagase +7 more | Research Square (Research Square)
<title>Abstract</title> Although previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and … <title>Abstract</title> Although previous studies have demonstrated the effects of concussions do not accumulate as the time interval between injuries increases, little is known about the relationship between this interval and the effects of repetitive concussions. The objective of this study is to explore the relationship between the time interval and changes in behavior and histology following repetitive concussions. Male adolescent rats received concussions by weight drop and were randomly assigned to one of four experimental groups, receiving concussions three times either daily, every other day, once per week, or once every 2 weeks. Only rats that received daily concussions exhibited cognitive impairment, while the other groups did not. No groups showed motor or anxiety-like impairments. Histological analysis revealed increased total and activated microglia, as well as astrogliosis, in the prefrontal cortex, corpus callosum, dentate gyrus, and cornu Ammonis 1 region of the hippocampus in rats subjected to daily concussions. Accumulation of phosphorylated tau was also observed in the prefrontal cortex and cornu Ammonis 1. Longer intervals between concussions may reduce the risk of cognitive impairment and limit microglial activation, astrogliosis, and phosphorylated tau accumulation. These findings may help guide decisions on the appropriate timing for return to play in humans.

Scutellarin Alleviates Cuprizone-Induced Demyelination by Improving Mitochondrial Dysfunction, Reducing Lipid Oxidation and Inhibiting the p38 MAPK Pathway

2025-06-12
Qiting Zhao , Yantuanjin Ma , Shufen Wang | Antioxidants
The occurrence of demyelination in the central nervous system (CNS) causes neurodegenerative lesions. The occurrence and development of demyelination involve multiple pathological mechanisms, including the generation of reactive oxygen species … The occurrence of demyelination in the central nervous system (CNS) causes neurodegenerative lesions. The occurrence and development of demyelination involve multiple pathological mechanisms, including the generation of reactive oxygen species (ROS) caused by mitochondrial dysfunction in microglia and subsequent neuroinflammation. Scutellarin is a natural flavonoid drug with significant neuroprotective effects, including antioxidant, anti-inflammatory, and anti-apoptotic properties, and is widely used in the treatment of neurological diseases. However, the protective effects and mechanisms of scutellarin on demyelination have not yet been elucidated. This study aims to investigate the neuroprotective effects of scutellarin on demyelination and its underlying molecular mechanisms. Our results showed that treatment with scutellarin significantly alleviated Cuprizone-induced myelin damage, neuronal apoptosis, and neurological deficits in mice. In in vitro experiments, scutellarin significantly reduced Cuprizone–copper-induced pro-inflammatory microglia formation and inhibited the secretion of TNF-α, thereby reducing myelin cell damage. Mechanism studies revealed that scutellarin inhibited the secretion of TNF-α by microglia and alleviated myelin cell damage by reducing the excessive production of mitochondrial reactive oxygen species (Mito-ROS), reactive oxygen species (ROS), and malondialdehyde (MDA) induced by Cuprizone–copper in microglia. Finally, scutellarin improved mitochondrial dysfunction in microglia and significantly alleviated myelin cell damage by inhibiting the expression of p38MAPK. In conclusion, our findings demonstrate that scutellarin exerts significant neuroprotective effects on Cuprizone-induced mice by improving mitochondrial dysfunction in microglia, thereby reducing inflammatory responses. This effect is closely associated with the inhibition of the p38MAPK pathway.

14. ĐÁNH GIÁ TÍNH TIN CẬY VÀ GIÁ TRỊ CỦA THANG ĐO KOREAN STANDARD PATTERN IDENTIFICATION FOR STROKE III PHIÊN BẢN TIẾNG VIỆT

2025-06-12
Nguyễn Thị Hướng Dương , Tăng Khánh Huy , Trần Bảo Ngọc +1 more | Tạp chí Y học Cộng đồng
Mục tiêu: Y học cổ truyền Việt Nam sử dụng phương pháp chẩn đoán hội chứng để chẩn đoán đột quỵ, nhưng vẫn chưa có công cụ chuẩn hóa. Thang … Mục tiêu: Y học cổ truyền Việt Nam sử dụng phương pháp chẩn đoán hội chứng để chẩn đoán đột quỵ, nhưng vẫn chưa có công cụ chuẩn hóa. Thang đo K-SPI-Stroke III của Hàn Quốc cung cấp một giải pháp, và do đó cần đánh giá tính khả thi áp dụng tại Việt Nam do sự khác biệt về văn hóa và thể chất. Đối tượng và phương pháp: Nghiên cứu được thực hiện qua hai giai đoạn. Giai đoạn 1 chuyển ngữ và thích ứng văn hóa thang đo K-SPI-Stroke III sang tiếng Việt, đánh giá tính giá trị nội dung (I-CVI và S-CVI: 100%; độ rõ ràng I-CVI: 80-100%, S-CVI/Ave: 99%, S-CVI/UA: 96%) và tính giá trị bề mặt. Giai đoạn 2 đánh giá độ tin cậy và giá trị với 66 bệnh nhân đột quỵ. Kết quả: Tính nhất quán nội bộ (Cronbach’s alpha: 0,78-0,84) và độ tin cậy lặp lại (hệ số Kappa câu hỏi: 0,43-0,86; tương quan thang đo phụ: 0,76-0,94) đều cao. Giá trị phân biệt cho thấy sự khác biệt đáng kể về điểm số giữa các hội chứng, với giá trị dự đoán đạt 62,1%. Kết luận: Phiên bản tiếng Việt của K-SPI-Stroke III thể hiện độ tin cậy và giá trị mạnh mẽ, hỗ trợ việc sử dụng trong nghiên cứu chẩn đoán đột quỵ bằng y học cổ truyền tại Việt Nam.

The converging paths to hippocampal sclerosis of ageing: insights from LATE-NC and vascular disease

2025-06-05
Ryan P Coburn , Hugo Botha | Brain
This scientific commentary refers to ‘Common neuropathologic change drivers of hippocampal sclerosis of ageing’ by Woodworth et al. (https://doi.org/10.1093/brain/awaf158). This scientific commentary refers to ‘Common neuropathologic change drivers of hippocampal sclerosis of ageing’ by Woodworth et al. (https://doi.org/10.1093/brain/awaf158).

Cerebrovascular alterations in a mouse model of late-onset Alzheimer’s disease

2025-06-05
Christian Crouzet , Danny F. Xie , Maiella Nona Laquindanum Nuqui +7 more | Neurophotonics
Alzheimer's disease (AD) is an age-related neurodegenerative disorder with cerebrovascular alterations contributing to cognitive decline. Assessing cerebrovascular changes in mouse models that mimic the human condition of late-onset, sporadic AD … Alzheimer's disease (AD) is an age-related neurodegenerative disorder with cerebrovascular alterations contributing to cognitive decline. Assessing cerebrovascular changes in mouse models that mimic the human condition of late-onset, sporadic AD is important for better human applicability. To assess cerebrovascular changes in three mouse models: (1) 3xTg-AD; (2) the humanized amyloid-beta knock-in ( hAβ -KI) mouse model of late-onset, sporadic AD; and (3) age-matched wild-type mice. We measured resting-state cerebral blood flow (CBF) and neurovascular coupling (NVC) using laser speckle imaging (LSI) and performed ex vivo analyses of gene expression and cerebrovascular structure using bulk ribonucleic acid sequencing and confocal microscopy, respectively. Our study identifies specific cerebrovascular alterations in the hAβ -KI mouse model, including increased resting-state CBF, a shift toward smaller blood vessel diameters, impaired NVC, and transcriptomic changes related to metabolism and inflammation. Notably, we found that the increased resting-state CBF was primarily associated with female hAβ -KI mice. Our findings demonstrate that the hAβ -KI mouse model exhibits cerebrovascular alterations that warrant further investigation to uncover the underlying mechanisms. Expanding these studies could enhance our understanding of cerebrovascular alterations in AD and support the development of targeted therapeutic strategies.

Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia

2025-06-03
Adnan Akif , T.T. Nguyen , Langni Liu +5 more | Fluids and Barriers of the CNS
As a key inflammatory factor, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation and the progression of neurodegenerative diseases. Dysregulation of NLRP3 … As a key inflammatory factor, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation and the progression of neurodegenerative diseases. Dysregulation of NLRP3 signaling can trigger various inflammatory responses in the brain, contributing to the development of neurodegenerative diseases such as ischemic stroke, vascular dementia (VaD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Therefore, the NLRP3 signaling pathway is a promising therapeutic target for the treatment of neurodegenerative diseases, including VaD. In this study, we investigated the therapeutic effects of a synthetic sulfonylurea NLRP3 inhibitor, AMS-17, in a VaD mouse model using bilateral common carotid artery stenosis (BCAS) and elucidated the underlying mechanisms. All mice were randomly divided into three groups: Sham, VaD + Vehicle, and VaD + AMS-17. Cognitive function was assessed using the Y-maze and Morris water maze (MWM) on the 50th day after BCAS. Brain sections and blood serum samples were collected for biomarker analysis and immunohistochemistry. Neurodegeneration, expressions of the molecules involved in the NLRP3 signaling pathways, tight junction proteins, and myelination were assessed using western blotting and immunofluorescence (IF). The levels of Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-4 (IL-4) in the blood were measured using ELISA. AMS-17 treatment improved cognitive function, enhanced blood-brain barrier (BBB) integrity, and promoted remyelination in VaD mice. Additionally, AMS-17 reduced neurodegeneration and decreased the expression of NLRP3 and its associated proteins, Apoptosis-associated speck-like protein (ASC), and cleaved caspase-1 in the brain. It also lowered pro-inflammatory TNF-α and IL-1β levels, while increasing the anti-inflammatory IL-4 level in the blood. The findings of this study provide the first promising evidence for the use of AMS-17 in VaD treatment in mice. This study introduces AMS-17 as a novel chemical scaffold with NLRP3 inhibitory activity, which can be further developed for the treatment of VaD in humans. Not applicable.

The Role of Phytochemicals in Age-Related Cognitive Decline: A Natural Solution for Brain Health

2025-06-01
Esther Ugo Alum , Daniel Ejim Uti , Simeon Ikechukwu Egba +2 more | Natural Product Communications
Age-related cognitive decline, characterized by memory loss, attention deficits, and reduced executive function, remains a major public health challenge, with limited pharmaceutical interventions offering symptomatic relief. Phytochemicals, bioactive compounds derived … Age-related cognitive decline, characterized by memory loss, attention deficits, and reduced executive function, remains a major public health challenge, with limited pharmaceutical interventions offering symptomatic relief. Phytochemicals, bioactive compounds derived from plants, have emerged as promising neuroprotective agents due to their antioxidant, anti-inflammatory, and neurogenic properties. This review explores the role of phytochemicals in mitigating cognitive deterioration through in vitro, in vivo, and clinical studies. Key compounds such as flavonoids, curcumin, resveratrol, and Ginkgo biloba derived compounds including; Ginkgolic Acids, terpenoids (Ginkgolides and Bilobalide), have demonstrated potential in reducing oxidative stress, modulating neuroinflammation, enhancing mitochondrial function, and improving neurotransmitter balance. However, challenges such as bioavailability, dose optimization, and clinical translation hinder their widespread adoption. Advances in delivery technologies, including nanoencapsulation and liposomal formulations, may enhance their therapeutic efficacy. Additionally, integrative strategies combining phytochemical-rich diets with lifestyle interventions, such as the Mediterranean and MIND diets, present a holistic approach to cognitive health. While preliminary findings are promising, further large-scale clinical trials are needed to validate the efficacy of phytochemicals in preventing and treating age-related cognitive decline. Understanding their mechanisms and overcoming translational barriers will facilitate their integration into mainstream healthcare as sustainable, natural alternatives to pharmacological treatments. By leveraging the neuroprotective potential of phytochemicals, future interventions could provide accessible and effective solutions for promoting brain health in aging populations.

Mediating role of Interleukin-6 in the predictive association of diabetes with Hippocampus atrophy, Amyloid, Tau, and Neurofilament pathology at pre-clinical stages of diabetes-related cognitive impairment

2025-06-01
Asma Hallab , Sid E. O’Bryant , Kristine Yaffe +7 more | Brain Behavior & Immunity - Health

Severity and Prognosis of Vascular Dementia in Patients with Acute Cerebral Infarction Combined with H-Type Hypertension and Its Correlation with Uric Acid Levels

2025-06-01
Hong Yang , Min Feng | Neuropsychiatric Disease and Treatment
To investigate the correlation between serum uric acid levels and the severity and prognosis of acute cerebral infarction (ACI) combined with vascular dementia (VD) in patients with H-type hypertension. A … To investigate the correlation between serum uric acid levels and the severity and prognosis of acute cerebral infarction (ACI) combined with vascular dementia (VD) in patients with H-type hypertension. A retrospective analysis was conducted on 150 patients with VD after acute ischemic stroke (AIS) admitted to the Second Affiliated Hospital of Bengbu Medical College from September 2021 to March 2023. Patients with H-type hypertension (n=84) formed the observation group, while those without (n=66) formed the control group. Uric acid levels were compared between groups. Based on cognitive function scores, patients were further classified into mild, moderate, and severe dementia subgroups, and differences in uric acid and homocysteine levels were analyzed. Prognosis was assessed in the observation group after three months of treatment using activities of daily living scores, and logistic regression was performed to identify prognostic factors. The observation group had significantly higher blood uric acid levels than the control group (P<0.05). Within the observation group, uric acid and homocysteine levels differed significantly among dementia severity subgroups (P<0.05) and were significantly higher than in the control group (P<0.01). MMSE scores were negatively correlated with uric acid and homocysteine levels. Logistic regression analysis identified uric acid as an independent risk factor for prognosis. Elevated serum uric acid levels in patients with ACI and H-type hypertension are associated with greater dementia severity and poorer prognosis, highlighting the importance of monitoring uric acid levels in these patients.

Corrigendum to “Nitro-Oleic acid protects from neovascularization, oxidative stress, gliosis and neurodegeneration in oxygen-induced retinopathy” [Redox Biol. 83 (2025) 103634]

2025-06-01
María V. Vaglienti , María Constanza Paz , María Victoria Gutiérrez +4 more | Redox Biology

Imaging Markers of Neuroinflammation in Aging and Alzheimer's Disease and Related Dementia: A Comprehensive Review

2025-06-01
Shefali Chaudhary , Herta H. Chao , Khushbu Agarwal +2 more | Neuroscience & Biobehavioral Reviews