Nrf2 is an astrocyte-enriched transcriptional factor that serves as a key regulator of endogenous cellular defense systems against oxidative stress and inflammation. This study aimed to determine whether Ginseng-pretreatment attenuates sensorimotor deficits and improves long-term recovery after ischemic stroke though the Nrf2 pathway activation by preferentially altering reactive astrogliosis.
   WT and Nrf2-/- mice were pretreated with Ginseng via gavage once daily for 7 days prior to permanent distal middle cerebral artery occlusion (pdMCAO). Neurobehavioral tests were performed to assess sensorimotor deficits and long-term recovery over 28 days, lesion volumes were determined, and immunohistochemical analysis was used to characterize the astrocytic and microglial activation in early stage of ischemic stroke onset (0-3 days). Specific Nrf2 downstream targeted antioxidant genes expressions were assessed by Western Blot.
   We first established a more sensitive method that can accurately assess long-term sensorimotor deficits after pdMCAO. Second, we revealed that Ginseng-pretreatment decreased sensorimotor deficits and promoted long-term recovery, reduced ischemic lesion volume (8.03±1.74% vs 12.62±0.81% on day 3), attenuated reactive astrogliosis at a spatiotemporal pattern but not microglia activation, and enhanced the induction of Nrf2-downstream proteins after ischemic injury in WT mice, which was essentially abolished in Nrf2 knockouts. Of interest, Nrf2 deficiency exacerbated the deterioration of ischemic damage.
   Together, Ginseng-pretreatment protects against acute ischemic sensorimotor deficits and promotes long-term recovery through Nrf2 activation by preferentially altering the spatiotemporal reactive astrogliosis.

Korean Red Ginseng Protects Against Long-term Sensorimotor Deficits After Ischemic Stroke Through The Nrf2 Pathway