Behavioural Inflexibility And White Matter Inflammation In An Aged hAPP Rat With Subcortical Stroke

The interactions between Alzheimer’s disease (AD) and ischemic stroke pathology are of key interest in the development of post-stroke cognitive decline. While clinical and experimental studies have suggested an interaction, the mechanisms whereby these conditions interact to worsen cognition haven’t been fully revealed. This study aimed to combine rodent models of AD and stroke in an aged rat and assess the behavioural and histological outcomes. An injection of endothelin-1 (ET-1), a potent vasoconstrictor into the basal ganglia of a rat with human amyloid precursor protein (hAPP) overexpression (F344Tg) was followed up 3 months later to assess behavioural flexibility, memory and anxiety phenotypes, followed by assessment of infarct size and microglia and astrocyte activity. At the chronic post-injury time-point, impaired behavioural flexibility was observed in F344Tg/ET-1 combined rats, while anxiety-like phenotypes, deficits in processing speed, and microglial activation in white matter tracts were increased in F344Tg rats with modest further perturbations driven by ET-1 injury. Persistent inflammation at the infarct site was observed to exist in ET-1 injured rats. The observed combined effects of APP and subcortical injury may shed light on the interactions between AD and ischemic stroke pathology observed in susceptible elderly populations by exposing possible interactions between white matter fibre tract integrity, subcortical stroke, and behavioural changes. Future studies will aim to better understand these mechanisms of interaction with the aim of therapeutic intervention to prevent post-stroke cognitive impairment in humans