A novel mouse model of light-mediated recanalization after stroke

Stroke is a leading cause of adult disability and the third leading cause of death. Despite expanding reperfusion treatment indications, a significant proportion of patients (54.5%) experience poor outcomes despite successful recanalization, emphasizing the need for a clinically relevant preclinical stroke model. In response, we developed a novel mouse model involving photothrombotic (PT) occlusion and light-induced recanalization of the distal branch of the middle cerebral artery (MCA), closely mimicking ischemic progression in clinical settings.The stable occlusion of the MCA's distal branch resulted in localized necrotic tissue in the cortex, with a measured lesion volume of 6.9 ± 0.1 mm3 one week post-PT. Evaluation of Evans Blue dye diffusion revealed extravasation 24 hours after PT, accompanied by increased water content in the ipsilesional hemisphere compared to the contralesional side and Sham mice. Functional impairment, assessed through the clasping test, decreased from two to seven days after stroke. Elevated levels of glial fibrillary acidic protein (GFAP) indicated reactive astrogliosis during the acute phase.In recanalized mice, UV LED illumination 30 minutes post-PT induced clot bond breakage and vasodilatation, fostering blood vessel recanalization. Preliminary data indicated reduced water content in the affected hemisphere compared to non-recanalized mice. Comprehensive behavioral tests highlighted complete motor function recovery 24 hours after stroke. This newly developed mouse model offers valuable insights into stroke pathology and treatment outcomes, providing a platform for further research and therapeutic advancements.