Targeting diaschisis to alleviate memory deficits after experimental stroke

Stroke is one of the most common central nervous system causes of morbidity and mortality. Cognitive impairment is a common and long-term consequence of stroke, with considerable impact on the quality of life. However, despite the high prevalence and importance of post-stroke cognitive dysfunction, there are currently no effective treatments directly aimed at improving or preventing cognitive dysfunction. Here, we show that small unilateral photothrombotic stroke in the murine motor cortex causes widespread bilateral increases in excitability assessed via c-Fos labelling. Increased activity in the hippocampal and prefrontal cortical regions was associated with pronounced deficits in object memory, but not working memory. Application of the anti-seizure drug eslicarbazepine acetate normalized the hyperexcitability and reversed post-stroke memory deficits. These data suggest that diaschisis, denoting remote effects of focal lesions, is associated even with small stroke lesions. Moreover, this study suggests that anti-seizure drugs can reduce abnormal excitability and improve cognition after experimental stroke. This finding may have implications for treatment of cognitive deficits in post-stroke patients, but this will require further confirmation by clinical studies.