Photothrombosis-induced cortical stroke mouse model produces focal electrographic epileptic human biomarkers

Interictal epileptiform spikes, high-frequency ripple oscillations, and their co-occurrence - spike ripples - in human scalp or intracranial voltage recordings are well-established epileptic biomarkers independent of etiology. While clinically significant, the neural mechanisms generating these electrographic events remain unclear. Stroke is a well-established risk factor for epilepsy with an estimated 11% of patients developing epilepsy within 5 years post-stroke. Cortical stroke induced via photothrombosis results in epilepsy in rats. As mice allow for cell-type specific analysis, we sought to determine whether focal cortical stroke in mice produces characteristic human epileptic biomarkers specific to the lesioned tissue. We induced unilateral focal stroke in the motor cortex using photothrombosis in the broadly used C57BL/6 mice and obtained intermittent bilateral local field potential recordings over many weeks. We observed spike, ripple, and spike ripple biomarkers in the peri-stroke mouse cortex that shared consistent morphology as humans with epilepsy. In addition, similar to humans, we found spike ripples detected using automated procedures developed from human intracranial recordings classified the pathological hemisphere with the highest sensitivity and specificity among the three biomarkers. Expert validation of the automatically detected biomarkers confirmed these observations. These results demonstrate a translational cortical stroke mouse model with a defined injury zone that produces localized electrographic biomarkers as in human epilepsy, enabling the investigation of the cellular and circuit mechanisms of pathologic interictal activity.