Abstract
BackgroundPost-stroke dementia (PSD) is one of the major consequences after stroke. Chronic cerebral hypoperfusion (CCH) can induce vascular cognitive impairment and potentiate amyloid pathology. We investigated how CCH contributes to the development of PSD after stroke in the context of neuroinflammation and amyloid pathology.MethodsWe designed a unique animal model for PSD. We performed middle cerebral artery occlusion (MCAO) surgery in rats mimicking acute territorial infarct, which was followed by bilateral common carotid artery occlusion (BCCAo) surgery mimicking CCH. We performed behavioral tests including neurologic function test and water maze task and histological investigations including neuroinflammation, neuronal cell death, amyloid pathology, and aquaporin 4 (AQP4) distribution.ResultsSpatial memory was synergistically impaired when BCCAo was superimposed on MCAO. Neuroinflammation with astroglial or microglial activation and amyloid pathology were enhanced in the ipsilateral cortex, thalamus, and hippocampus when BCCAo was superimposed on MCAO. Glymphatic pathway-related AQP4 distribution changed from perivascular to parenchymal pattern.ConclusionsOur experimental results suggest that CCH may contribute to the development of PSD by interfering with amyloid clearance through the glymphatic pathway and concomitant neuroinflammation. Therapeutic strategy to clear brain metabolic waste through the glymphatic pathway may be a promising approach to prevent PSD after stroke.
Highlights
Post-stroke dementia (PSD) is one of the major consequences after stroke
Considering the nature of PSD developing after stroke, PSD may be more related to VD including strategic infarct dementia, multi-infarct dementia, subcortical ischemic vascular dementia, hypoperfusion dementia, or mixed dementia rather than pure neurodegenerative dementia such as Alzheimer’s disease (AD) [4]
We investigated how Chronic cerebral hypoperfusion (CCH) contributes to the development of PSD after stroke in the context of neuroinflammation and amyloid pathology
Summary
Post-stroke dementia (PSD) is one of the major consequences after stroke. Chronic cerebral hypoperfusion (CCH) can induce vascular cognitive impairment and potentiate amyloid pathology. We investigated how CCH contributes to the development of PSD after stroke in the context of neuroinflammation and amyloid pathology. More than half of stroke survivors experience residual physical disability or cognitive decline [2]. Even in physically independent survivors, cognitive decline can be a major hurdle in returning to the premorbid social life. The pathophysiology of dementia is complicated and heterogeneous including vascular dementia (VD), Alzheimer’s disease (AD), or mixed dementia [5]. Considering the nature of PSD developing after stroke, PSD may be more related to VD including strategic infarct dementia, multi-infarct dementia, subcortical ischemic vascular dementia, hypoperfusion dementia, or mixed dementia rather than pure neurodegenerative dementia such as AD [4].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
