Post-stroke dementia (PSD) is a major neurodegenerative consequence of stroke. Tauopathy has been reported in diverse neurodegenerative diseases. We investigated cognitive impairments and pathomechanisms of tauopathy in a rat model of PSD by modeling acute ischemic stroke and underlying chronic cerebral hypoperfusion (CCH) in the same animal. We performed middle cerebral artery occlusion (MCAO) surgery in rats, to mimic acute ischemic stroke, followed by bilateral common carotid artery occlusion (BCCAo) surgery, to mimic CCH. We performed behavioral tests and focused on the characterization of tauopathy through histology. Parenchymal infiltration of cerebrospinal fluid (CSF) tracers after intracisternal injection was examined to evaluate glymphatic clearance. In an animal model of PSD, cognitive impairment was aggravated when BCCAo was superimposed on MCAO. Tauopathy, manifested by tau hyperphosphorylation, was prominent in the penumbra when CCH was combined with acute ischemic stroke. Synergistic accentuation of tauopathy was more evident in the white matter. Oligodendrocytes and some neurons were colocalized with tau hyperphosphorylation. Parenchymal infiltration of CSF tracers was attenuated in the PSD model. Our experimental results suggest that CCH may aggravate cognitive impairment and tau hyperphosphorylation in a rat model of PSD by interfering with tau clearance through glymphatic pathway. Therapeutic strategies to improve clearance of brain metabolic wastes, including tau, may be a promising approach to prevent PSD after stroke.
Protective Role of S-Nitrosoglutathione (GSNO) Against Cognitive Impairment in Rat Model of Chronic Cerebral Hypoperfusion
