Neuronal biomarkers associated with recovery of motor function in a mouse model of stroke

Ischemic stroke, a major cause of adult disability, is characterized by an occlusion of cerebral blood vessels, leading to neurological impairment. After a stroke, the neural circuits in the peri-infarct zone undergo plastic changes to allow a spontaneous restoration of the neurological function. However, the extent of spontaneous recovery is highly variable among patients, underscoring the need for identifying neurophysiological biomarkers that can predict recovery outcomes, thus aiding effective treatment strategies. In this thesis work, I employed a well-established model of ischemic stroke in mice, the distal middle cerebral artery occlusion (dMCAO), to investigate the relationship between motor deficits and cortical changes after stroke in the peri-infarct area. Behavioral tests (rotarod, grip strength, and gridwalk) were conducted at various intervals post-stroke (D02, D09, D30) to evaluate the evolution of motor performance. I observed that dMCAO does not significantly impact muscle force or motor coordination and balance, as assessed by the grip strength and the rotarod test, but does induce deficits in fine motor behavior, unmasked by the gridwalk test. After determining the extent of the behavioral impairment with the gridwalk test, subjects were classified as either good or poor recoverers. To explore the potential correlations between behavioral impairments and neural changes, I performed both spontaneous and evoked in vivo local field potential (LFP) recordings in anesthetized Thy1-ChR2-YFP transgenic mice, at D30, the chronic phase of stroke. I found that stroke mice displayed a substantial reduction of the total frequency power in comparison to the control group, and mice with poor recovery outcomes demonstrated decreased excitability in response to ipsilesional premotor cortex stimulation, contrasted by heightened responses to contralateral primary motor cortex stimulation. Altogether my data shed light on potential mechanisms about the ‘good’ and ‘poor’ recovery outcomes of the motor function, thus opening new perspectives for further preclinical investigations.