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• W2131036135 abstract "Small vessel disease (SVD) of the brain is a leading cause of age- and hypertension-related cognitive decline and disability. Cerebral white matter changes are a consistent manifestation of SVD on neuroimaging, progressing silently for many years before becoming clinically evident. The pathogenesis of these changes remains poorly understood, despite their importance. In particular, their pathological correlate at early stages remains largely undefined. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), caused by dominant mutations of the NOTCH3 receptor, is regarded as a paradigm for the most common form of sporadic SVD. In this study, we used immunohistochemistry, confocal microscopy and electron microscopy, together with qualitative and quantitative analyses to assess oligodendroglial, axon and myelin damage in TgPAC-Notch3R169C mice, a model of preclinical CADASIL.The principal cerebral white matter changes in TgPAC-Notch3R169C mice are microvacuoles (≤ 1 μm diameter) in the myelin sheaths associated with focal myelin degradation and occurring in the absence of oligodendrocyte loss. Half the damaged myelin sheaths still contain an apparently intact axon. Clearance of myelin debris appears inefficient, as demonstrated by the significant but mild microglial reaction, with occasional myelin debris either contacted or internalized by microglial cells.Our findings suggest that segmental intramyelinic oedema is an early, conspicuous white matter change in CADASIL. Brain white matter intramyelinic oedema is consistently found in patients and mouse models with compromised ion and water homeostasis. These data provide a starting point for novel mechanistic studies to investigate the pathogenesis of SVD-related white matter changes." @default.
• W2131036135 created "2016-06-24" @default.
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• W2131036135 date "2014-04-30" @default.
• W2131036135 modified "2023-10-18" @default.
• W2131036135 title "Early white matter changes in CADASIL: evidence of segmental intramyelinic oedema in a pre-clinical mouse model" @default.
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• W2131036135 doi "https://doi.org/10.1186/2051-5960-2-49" @default.
• W2131036135 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4035092" @default.
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