Capturing longitudinal impacts on cognition following stroke in rodent models using touchscreen testing

Abstract

AbstractBackgroundUp to two thirds of ischaemic stroke survivors develop cognitive impairment, predominantly impacting executive and attentional processing. Animal models are essential for effective translation and development of therapies. However, accurately modelling cognitive dysfunction in animal models of stroke has been limited. To address this, we aimed to longitudinally examine changes in attentional processing, spatial working memory and processing speed using two rodent ischemic injury models: the middle cerebral artery occlusion (MCAO) in C57BL/6J mice and the endothelin‐1 injury in Long Evans rats.MethodUsing the rodent touchscreen cognitive platform, we assessed attention in mice and rats employing the Continuous Performance Task (CPT) paradigm, and spatial working memory in mice using the trial unique non‐matching to location (TUNL) paradigm. Cognitive performance in adult mice and rats was assessed before inducing stroke, and at 4, 12, 24, 36 and 48 weeks post‐injury.ResultMice exposed to MCAO showed robust, long‐lasting deficits in attentional processing and spatial working memory post‐stroke. In comparison, we observed no changes in attentional processing following endothelin‐1 injury to the motor cortex in rats.ConclusionOur findings provide the first evidence for longitudinal cognitive changes in a rodent model of stroke, recapitulating that observed in the clinic. Our results identify a valuable model and behavioural approach to advance mechanistic understandings of the trajectory of cognitive dysfunction following stroke, and provide a platform with which to identify novel therapies. Moreover, our work further strengthen the need for preclinical animal studies to assess different species and injury models that are critically needed for better modelling clinical stroke and truly enabling the translation of research targeting cognitive symptoms.