Electroacupuncture protects against cerebral ischemia-reperfusion injury via regulating P2×7R expression

Ischemic stroke is a serious clinical condition that is challenging to cure; therefore, slowing down the depletion of ATP is crucial to enhancing the tolerance of ischemic tissue through preconditioning. Electroacupuncture (EA) preconditioning induces tolerance to cerebral ischemia; however, the underlying mechanism remains unclear.

The P2×7 receptor (P2×7R) mediates the stimulation of microglial cells and is involved in the development of cerebral ischemia-reperfusion (I/R) damage. We hypothesized that the protective effect of EA preconditioning is associated with the downregulation of P2×7R expression.

We performed EA at the "Baihui" and "Fengfu" for 30 min before establishing a rat model of cerebral I/R induced based on the middle cerebral artery occlusion model (MCAO). MCAO rats were administered a ventricular injection of 2 '(3')-O-(4-benzoyl) adenosine triphosphate (BzATP), a P2×7R agonist, 30 min before EA. Neurologic scoring, infarction volume, and expression of cytokines, Bcl-2 and Bax, Iba1, P2×7R, p38, and phosphorylated p38 (p-p38) in ischemia penumbra were detected 24 h after cerebral I/R.

EA preconditioning ameliorated neurologic scoring, decreased infarction volume, and neuronal injury, and decreased cytokine release, while BzATP exacerbated cerebral I/R damage and inflammation events, unlike the favorable efficacy of EA. EA inhibited the expression of Iba-1, P2×7R, and p-p38/p38 in the ischemic penumbra, whereas BzATP reversed this effect.

EA could induce cerebral tolerance to I/R damage by suppressing P2×7R expression and release of inflammatory factors.