Targeting diaschisis to alleviate memory deficits after experimental stroke

Area of Science:

• Neuroscience
• Neurology
• Pharmacology

Background:

• Stroke is a leading cause of death and disability, frequently resulting in long-term cognitive impairment.
• Current treatments for post-stroke cognitive dysfunction are limited, highlighting an unmet clinical need.

Purpose of the Study:

• To investigate the effects of small focal stroke lesions on brain excitability and cognitive function.
• To evaluate the therapeutic potential of anti-seizure medication in mitigating post-stroke cognitive deficits.

Main Methods:

• Induction of small unilateral photothrombotic stroke in the murine motor cortex.
• Assessment of widespread brain excitability using c-Fos labelling.
• Evaluation of cognitive function, specifically object and working memory.
• Administration of eslicarbazepine acetate to assess its impact on hyperexcitability and memory.

Main Results:

• Small strokes induced bilateral increases in neuronal excitability, particularly in hippocampal and prefrontal regions.
• Significant deficits in object memory, but not working memory, were observed post-stroke.
• Eslicarbazepine acetate treatment normalized brain hyperexcitability and ameliorated memory deficits.

Conclusions:

• Even small stroke lesions can trigger remote neuronal network dysfunction (diaschisis).
• Targeting abnormal brain excitability with anti-seizure drugs shows promise for improving cognition after stroke.
• Findings suggest a potential therapeutic strategy for post-stroke cognitive impairment, warranting further clinical investigation.