Effects of electroacupuncture on the functionality of NG2-expressing cells in perilesional brain tissue of mice following ischemic stroke

Neural/glial antigen 2(NG2)-expressing cells has multipotent stem cell activity under cerebral ischemia.Our study examined the effects of electroacupuncture(EA)therapy(2 Hz,1 or 3 mA,20 minutes)at the Sishencong acupoint on motor function after ischemic insult in the brain by investigating the rehabilitative potential of NG2-derived cells in a mouse model of ischemic stroke.EA stimulation alleviated motor deficits caused by ischemic stroke,and 1 mA EA stimulation was more efficacious than 3 mA EA stimulation or positive control treatment with edaravone,a free radical scavenger.The properties of NG2-expressing cells were altered with 1 mA EA stimulation,enhancing their survival in perilesional brain tissue via reduction of tumor necrosis factor alpha expression.EA stimulation robustly activated signaling pathways related to proliferation and survival of NG2-expressing cells and increased the expression of neurotrophic factors such as brain-derived neurotrophic factor,tumor growth factor beta,and neurotrophin 3.In the perilesional striatum,EA stimulation greatly increased the number of NG2-expressing cells double-positive for oligodendrocyte,endothelial cell,and microglia/macrophage markers(CC1,CD31,and CD68).EA therapy also greatly activated brain-derived neurotrophic factor/tropomyosin receptor kinase B and glycogen synthase kinase 3 beta signaling.Our results indicate that EA therapy may prevent functional loss at the perilesional site by enhancing survival and differentiation of NG2-expressing cells via the activation of brain-derived neurotrophic factor-induced signaling,subsequently ameliorating motor dysfunction.The animal experiments were approved by the Animal Ethics Committee of Pusan National University(approval Nos.PNU2019-2199 and PNU2019-2884)on April 8,2019 and June 19,2019.