Electroacupuncture confers beneficial effects through ionotropic glutamate receptors involving phosphatidylinositol-3 kinase/Akt signaling pathway in focal cerebral ischemia in rats

Abstract

Aim of the studyWe investigated the molecular mechanisms underlying the beneficial effects of electroacupuncture (EA) to cerebral ischemia in a rat middle cerebral artery occlusion (MCAO) model. Materials and methodsEA stimulation (2Hz, 1mA) was needle-delivered for 30min at acupoints corresponding to Baihui (GV20) and Qihai (CV6) in men in MCAO rats and was analyzed by an infarct volume, Western blot and immunohistochemical assay. ResultsEA stimulations strongly reduced infarct volume and improved neurological outcome after stroke. When we focused on the glutamate-evoked excitotoxic injury with coupled pathways, N-methyl-d-aspartate receptor (NMDAR) NR2A and NR2B and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluR2 subunit phosphorylation were significantly arrested by EA treatment in the parietal cortex of the brain. On the contrary, phosphatidylinositol-3 kinase (PI3K) and Akt phosphorylation markedly increased. Treatment of MCAO rats with the selective PI3K inhibitor LY-294002 to confirm the signaling pathway involved in EA neuroprotection revealed abrogated neuroprotective effects induced by EA. ConclusionThese results suggest that the beneficial effects of EA were associated with reduction of NMDAR and AMPAR phosphorylation and with activation of PI3K/Akt pathway. The PI3K/Akt pathway may mainly contribute to EA-induced neuroprotection after stroke.