White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies

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• 作者：Poornima Venkat^a ; ^b ; Michael Chopp^a ; ^b ; Alex Zacharek^a ; Chengcheng Cui^a ; Li Zhang^a ; Qingjiang Li^a ; Mei Lu^c ; Talan Zhang^d ; Amy Liu^a ; Jieli Chen^a ; ^e ; ^{jieli@neuro.hfh.edu}
• 关键词：Vascular dementia ; Aquaporin-4 ; White matter ; Glymphatic system ; Multiple microinfarction
• 刊名：Neurobiology of Aging
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：50
• 期：Complete
• 页码：96-106
• 全文大小：6127 K
• 卷排序：50

文摘

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p < 0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits.