NEURONAL ACTIVITY PATTERNS PREDICT CORTICAL VIABILITY IN A RODENT MODEL OF ISCHEMIC STROKE

Stroke is the fifth leading cause of death in the United States, and the majority of cases are due to Middle Cerebral Artery (MCA) ischemia (Mozaffarian et al., 2016). Improved treatments for MCA ischemia are necessary as current therapeutic strategies are only effective for a subset of stroke patients and only reduce damage or its functional consequences. Previous studies from our laboratory have demonstrated that sensory stimulation delivered within 2 hours (‘early treatment’) after permanent MCA occlusion (pMCAO) completely protects the cortex from impending stroke damage, whereas the same intermittent sensory stimulation results in exacerbated damage if delivered 3 or more hours after ischemic onset (‘late treatment’) (reviewed in Frostig et al., 2012). The interaction between sensory stimulation treatment and post-ischemic neuronal network activity is unknown but may be important for understanding the underlying mechanism of sensory stimulation treatment. Using a 32 microelectrode array spanning across horizontal S1 locations and cortical layers, this research generates for the first time a continuous spatiotemporal profile of multiunit activity (MUA) and local field potentials (LFP) from the MCA territory before (baseline) and directly after (0-5 hours) MCA occlusion in early stimulated, late stimulated, and pMCAO alone groups. Spatiotemporal synchrony, a measure of coordinated neuronal network activity across recording locations, is increased directly after pMCAO and is persistently high throughout the acute post-pMCAO period in pMCAO alone animals. Our data further indicate that high post-pMCAO spatiotemporal synchrony is reduced and baseline spatiotemporal synchrony is reestablished in early treated but not late treated animals. As synchrony is known to be important for cortical function and relevant to many pathological brain states, enhanced spatiotemporal synchrony may be a signature of cortical network dysfunction after pMCAO and predictive of whether damage has incurred after pMCAO and sensory stimulation treatment. Despite histological and synchrony related differences between early and late treated animals, evoked neuronal activity recovers during sensory stimulation treatment in both early and late treated groups, demonstrating that the damage sustained in late treated animals is delayed for hours after pMCAO. Following pMCAO, future ischemic stroke can be predicted from correlated neuronal network activity even before evoked activity is affected. This study is supported by NIH Grant NS066001 and Leducq Foundation Grant 15CVD02.