Cortical Reorganization and Sensorimotor Recovery in a Mouse Model of Intracerebral Hemorrhagic Stroke

Abstract

Intracerebral haemorrhage (ICH) is a subtype of stroke that accounts for approximately 10-15% of stroke cases in Canada. Neurological deficits following ICH are common and most patients will suffer long-term impairments. Spontaneous recovery facilitated by the remodeling of functional areas through neuronal reorganization has been observed in both stroke patients and animal models. However, the precise relationship between cortical remodeling and functional recovery is not completely understood. This thesis aims to characterize the reorganization of the sensorimotor cortex as well as quantify sensorimotor function longitudinally during the recovery period. Young Thy1-Chr2-YFP mice with an implanted chronic window over the intact skull allowed visualization of sensorimotor cortex functional assessments through light-based motor mapping and intrinsic signal optical imaging over a 6-week period. Additionally, a battery of behavioral tests was conducted in parallel to evaluate motor deficits. Following a striatal ICH, behavioral impairments were observed with both acute and chronic recovery. The deficits shown in ICH mice were linked with a disruption of motor maps. When stimulating the injured hemisphere, evoked movement of both forelimbs showed smaller amplitude compared to sham animals, which was accompanied with a reduction in the motor map size. On the other side, the contralesional hemisphere did not show any differences compared to the sham animals, demonstrating a potential compensatory mechanism. A trend toward recovery in the motor maps occurred on the 6th week, matching the late recovery of impaired forelimb use deficit. Conversely, the sensory responses evoked from mechanical forelimb stimulation did not show any changes following ICH induction. This is the first study to investigate the longitudinal impact of striatal ICH on bilateral sensorimotor maps in relation to behavioral deficits. Our findings revealed that injury in the striatum leads to long-term functional impact in the motor cortex accompanied by behavioral motor deficits, with a recovery of motor functions matching the recovery initiation in motor representations.