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1.
Geroscience ; 46(4): 3779-3800, 2024 08.
Article in English | MEDLINE | ID: mdl-38319539

ABSTRACT

Cerebral small vessel diseases (CSVD) are neurological disorders associated with microvessels, manifested pathologically as white matter (WM) changes and cortical microbleeds, with hypertension as a risk factor. Additionally, a high-fat diet (HFD) can affect peripheral vessel health. Our study explored how HFD affects cerebral small vessels in normotensive WKY, hypertensive SHR, and SHR/SP rats. The MRI results revealed that HFD specifically increased WM hyperintensity in SHR/SP rats. Pathologically, it increased WM pallor and vacuolation in SHR and SHR/SP rats. Levels of blood-brain barrier (BBB) protein claudin 5 were decreased in SHR and SHR/SP compared to WKY, with HFD having minimal impact on these levels. Conversely, collagen IV levels remained consistent among the rat strains, which were increased by HFD. Consequently, HFD caused vessel leakage in all rat strains, particularly within the corpus callosum of SHR/SP rats. To understand the underlying mechanisms, we assessed the levels of hypoxia-inducible factor-1α (HIF-1α), Gp91-phox, and neuroinflammatory markers astrocytes, and microglia were increased in SHR and SHR/SP compared to WKY and were further elevated by HFD in all rat strains. Gp91-phox was also increased in SHR and SHR/SP compared to WKY, with HFD causing an increase in WKY but little effect in SHR and SHR/SP. In conclusion, our study demonstrates that HFD, in combined with hypertension, intensifies cerebral pathological alterations in CSVD rats. This exacerbation involves increased oxidative stress and HIF-1α in cerebral vessels, triggering neuroinflammation, vascular basement membrane remodeling, IgG leakage, and ultimately WM damage.


Subject(s)
Cerebral Small Vessel Diseases , Diet, High-Fat , Rats, Inbred SHR , Rats, Inbred WKY , Animals , Cerebral Small Vessel Diseases/pathology , Cerebral Small Vessel Diseases/etiology , Diet, High-Fat/adverse effects , Rats , Male , Blood-Brain Barrier/pathology , Magnetic Resonance Imaging , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Claudin-5/metabolism , Disease Models, Animal , White Matter/pathology , NADPH Oxidase 2/metabolism , Hypertension/pathology
2.
J Neurol Sci ; 448: 120642, 2023 05 15.
Article in English | MEDLINE | ID: mdl-37030186

ABSTRACT

BACKGROUND: The use of a combination of stroke predictors, such as clinical factors and asymptomatic lesions on brain magnetic resonance imaging (MRI), may improve the accuracy of stroke risk prediction. Therefore, we attempted to develop a stroke risk score for healthy individuals. METHODS: We investigated the presence of cerebral stroke in 2365 healthy individuals who underwent brain dock screening at the Health Science Center in Shimane. We examined the factors that contributed to stroke and attempted to determine the risk of stroke by comparing background factors and MRI findings. RESULTS: The following items were found to be significant risk factors for stroke: age (≥60 years), hypertension, subclinical cerebral infarction, deep white matter lesion, and microbleeds. Each item was scored with 1 point, and the hazard ratios for the risk of developing stroke based on the group with 0 points were 17.2 (95% confidence interval [CI] 2.31-128) for 3 points, 18.1 (95% CI 2.03-162) for 4 points, and 102 (95% CI 12.6-836) for 5 points. CONCLUSIONS: A precise stroke prediction score biomarker can be obtained by combining MRI findings and clinical factors.


Subject(s)
Brain Ischemia , Stroke , Humans , Middle Aged , Prognosis , Stroke/diagnostic imaging , Stroke/etiology , Stroke/pathology , Risk Factors , Brain/diagnostic imaging , Brain/pathology , Brain Ischemia/pathology , Magnetic Resonance Imaging
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