Sciatic Nerve Stimulation Attenuates Intracranial Inflammation and Neuronal Injury in Acute Ischemic Stroke

Ischemic stroke, a leading cause of neurological disability, occurs due to cerebrovascular occlusion, resulting in cerebral ischemia and hypoxia that lead to neurological deficits. In the acute phase, neuronal injury and exacerbated intracranial inflammation contribute to disease progression. Effective modulation of inflammation and reduction of neuronal damage during this critical period are essential for improving stroke outcomes.A middle cerebral artery occlusion (MCAO) mouse model was established. The effects of sciatic nerve electrical stimulation on intracranial inflammation and neural injury in the acute phase after stroke were evaluated using immunostaining, enzyme-linked immunosorbent assay (ELISA), and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Furthermore, transcriptomic sequencing, immunostaining, ELISA, and TTC staining were employed to assess the outcomes of optogenetic activation of Prokr2-positive neuronal subpopulations within the sciatic nerve on intracranial inflammation and neural injury. Sciatic nerve stimulation was found to ameliorate intracranial inflammation and neuronal damage, as evidenced by reduced microglial activation, decreased pro-inflammatory cytokine levels, smaller cerebral infarct volume, and attenuated neuronal injury. Optogenetic activation of Prokr2-positive somatosensory neurons in the sciatic nerve induced distinct transcriptomic changes in the brain, attenuated acute inflammation, and promoted neuronal homeostasis. This study demonstrates that sciatic nerve stimulation alleviates intracranial inflammation and neuronal injury during the acute phase of ischemic stroke.