Neurovascular function recovery after focal ischemic stroke by enhancing cerebral collateral circulation via peripheral stimulation-mediated interarterial anastomosis

Abstract. Current treatments for ischemic stroke have focused on the administration of a tissue plasminogen activator, although the associated side effects and subsequent reperfusion injury remain challenging. Peripheral electrical stimulation has shed light on therapeutic interventions for ischemia by increasing cerebral blood flow (CBF) to the target region through collateral circulation, although the mechanism remains elusive. Here, a focal photothrombotic ischemic (PTI) stroke was induced in the right hemispheric primary somatosensory forelimb cortex (S1FL) of rat brains, and the therapeutic effects of forelimb and hindlimb stimulation were characterized at the contralesional S1FL. We observed that PTI stroke rats that received forelimb stimulation exhibited significantly restored CBF of the ischemic penumbra (1.06±0.25 for the S1FL and 0.99±0.14 for the primary somatosensory hindlimb cortex, respectively), electrocorticography (ECoG) delta band coherence of the intercortical S1FL (0.93±0.04) at the 75th min poststroke and an ischemic infarct (7.3±0.2  mm3) via collateral circulation recruitment. Importantly, anterior cerebral artery/middle cerebral artery (ACA–MCA) interarterial anastomotic regulation occurred upon forelimb stimulation and played roles in the recovery of neurovascular functions. These results indicated that receptive field-specific stimulation further restores CBF, neuronal activities, and tissue viability through the enhancement of ACA–MCA interarterial anastomosis-mediated collateral circulation and provides a feasible therapeutic intervention for stroke recovery.