Electroacupuncture Attenuates Ischemic White Matter Injury by Activating the Nrf2/HO-1 Axis and Suppressing Reactive Astrocyte Overactivation

Abstract

Background

White matter injury (WMI) is a major contributor to neurological dysfunction following ischemic stroke. Electroacupuncture (EA) has been shown to alleviate ischemic WMI and improve neurological deficits; however, the underlying mechanisms remain unclear.

Objective

In this study, we investigated whether EA exerts therapeutic effects on ischemic WMI by regulating the Nrf2/heme oxygenase-1 (HO-1) axis as well as reactive astrocyte (AS) activity.

Methods

Male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO) using the intraluminal filament method. Neurological function was assessed using the modified neurological severity score. Luxol Fast Blue staining was used to evaluate corpus callosum (CC) damage. Western blot and immunohistochemistry were used to detect the expression of Nrf2, HO-1, and glial fibrillary acidic protein (GFAP). Quantitative real-time polymerase chain reaction was used to assess the release of pro-inflammatory cytokines.

Results

EA significantly increased the expression of Nrf2 and HO-1 in the CC and effectively suppressed GFAP overexpression and the release of pro-inflammatory cytokines TNF-α and IL-1β, thereby improving myelin damage and neurological deficits in pMCAO rats. These beneficial effects of EA were abolished by the Nrf2 inhibitor luteolin.

Conclusion

Inactivation of the Nrf2/HO-1 axis and excessive activation of reactive AS accompanied by pro-inflammatory cytokine release may be critical contributors to ischemic WMI. EA may exert therapeutic effects by activating the Nrf2/HO-1 axis, inhibiting excessive AS activation, and inducing the release of inflammatory cytokines.