Artery targeted photothrombosis widens the vascular penumbra, instigates peri-infarct neovascularization and models forelimb impairments

The photothrombotic stroke model generates localized and reproducible ischemic infarcts that are useful for studying recovery mechanisms, but its failure to produce a substantial ischemic penumbra weakens its resemblance to human stroke. We examined whether a modification of this approach, confining photodamage to arteries on the cortical surface (artery-targeted photothrombosis), could better reproduce aspects of the penumbra. Following artery-targeted or traditional photothrombosis to the motor cortex of mice, post-ischemic cerebral blood flow was measured using multi-exposure speckle imaging at 6, 48, and 120 h post-occlusion. Artery-targeted photothrombosis produced a more graded penumbra at 48 and 120 h. The density of isolectin B4+ vessels in peri-infarct cortex was similarly increased after both types of infarcts compared to sham at 2 weeks. These results indicate that both models instigated post-ischemic vascular structural changes. Finally, we determined whether the strength of the traditional photothrombotic approach for modeling upper-extremity motor impairments extends to the artery-targeted approach. In adult mice that were proficient in a skilled reaching task, small motor-cortical infarcts impaired skilled-reaching performance for up to 10 days. These results support that artery-targeted photothrombosis widens the penumbra while maintaining the ability to create localized infarcts useful for modeling post-stroke impairments.