Cortical hemodynamics and motor recovery after cortical infarcts

Stroke is the leading cause of disability and the fourth leading cause of death in the United States. Of those that survive a stroke, many are left with long term functional motor impairments. Spontaneous recovery of motor function occurs after a stroke and the reorganization of spared neural tissue is a contributing factor. To study motor recovery following a stroke, rodent models have been especially useful because experimental manipulations can be paired with controlled infarcts to understand physiologically relevant changes. For example, stroke to the sensory-motor cortex (SMC) in mice produces functional motor impairments which are dependent on the reorganization of the remaining cortex. Ironically, after about 20 years of research on the reorganization of the peri-lesion following cortical ischemia, there has been a lack of focus on the neuro-vascular changes as they relate to functional outcome after stroke. The central hypothesis of this report is that spontaneous vascular remodeling contributes to behavioral recovery and cortical reorganization following ischemic insult. To investigate the relationship between blood flow recovery and improvement of motor function after an ischemic insult, we developed a mouse model of upper extremity impairment after a stroke that can be repeatedly imaged in vivo. Specifically, 14 C57/BL6 mice either received photo-thrombotic cortical lesions (n=7) or vehicle procedures (n=7), were allowed 3 days to recover, and then received forelimb function probes using the pasta matrix reaching task (PMRT), an assay for skilled forelimb function, in tandem with the imaging of cortical blood flow using multi-exposure speckle imaging (MESI) at Days 3, 5, 10, and 20. Results indicate that the mice that received injections with Rose Bengal displayed significantly decreased performance on the PMRT and a significantly reduced amount of cortical blood flow compared to both their baseline performance and the control group. Skilled forelimb performance following the ischemic lesion correlated strongly with stroke severity (as indexed by cortical blood flow in the lesion core 2 hours following lesion induction). Additionally, the re-establishment of cortical blood flow to the infarct core precedes the recovery of motor performance, indicating potential importance for the re-establishment of blood flow to support the adaptive plasticity required for motor recovery.