In vivo characterization of putative neuronal biomarkers for recovery in a mouse model of adult stroke

Stroke is a leading cause of long-term disability including impaired motor function worldwide. During a “critical period” after stroke, in the peri-infarct zone neural circuits undergo plastic changes to allow a spontaneous restoration of the neurological function. However, recovery outcomes among patients are highly variable, only partially depending on structural and functional factors related to the damage, such as the lesion location, volume and the topology of the neural connectivity within the peri-infarct zone. Currently, finding neurophysiological biomarkers to promptly predict recovery outcomes is a major challenge. To address this demand, we used a mouse model for ischemic injury (middle cerebral artery occlusion, MCAO) and investigated putative biomarkers at both behavioral and functional level. To evaluate the recovery outcomes, we characterized the motor function impairments by performing the gridwalk test in MCAO- and sham-mice at different days (D) after stroke induction (D2, D9, D16, D23, and D30) which revealed higher motor deficits in MCAO-mice compared to controls. Moreover, to investigate whether the recovery outcome of each animal could be reflected in neural connectivity, we performed in vivo electrophysiological recordings of local field potentials (LFPs) from the peri-infarct zone, i.e. the forelimb primary motor cortex. To investigate neuronal changes of inter- and intra-hemispheric connectivity, spontaneous and evoked activity were characterized at D9 and D30, the subacute and chronic (D30) phases of stroke, respectively. Our findings revealed higher amplitude responses to intra-hemispheric stimulation in stroke mice with a good recovery outcome, suggesting a possible correlation between higher neuronal plasticity and the recovery of the motor function.