Electroacupuncture attenuates cerebral ischemia/reperfusion injury by regulating oxidative stress, neuronal death and neuroinflammation via stimulation of PPAR-γ.

BACKGROUND: Oxidative stress and inflammatory responses play essential roles in cerebral ischemia/reperfusion (I/R) injury. Electroacupuncture (EA) is widely used as a rehabilitation method for stroke in China; however, the underlying mechanism of action remains unclear. Peroxisome proliferator-activated receptor gamma (PPAR-γ) has been reported to impact anti-inflammatory and anti-oxidative effects. OBJECTIVE: This study investigated the role of PPAR-γ in EA-mediated effects and aimed to illuminate its possible mechanisms in cerebral I/R. METHODS: In this study, male Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury were treated with EA at LI11 and ST36 for 30 min daily after MCAO/R for seven consecutive days. The neuroprotective effects of EA were measured by neurobehavioral evaluation, triphenyltetrazolium chloride staining, hematoxylin-eosin staining and transmission electron microscopy. Oxidative stress, inflammatory factors, neural apoptosis and microglial activation were examined by enzyme-linked immunosorbent assay, immunofluorescence and reverse transcriptase polymerase chain reaction. Western blotting was used to assess PPAR-γ-mediated signaling. RESULTS: We found that EA significantly alleviated cerebral I/R-induced infarct volume, decreased neurological scores and inhibited I/R-induced oxidative stress, inflammatory responses and microglial activation. EA also increased PPAR-γ protein expression. Furthermore, the protective effects of EA were reversed by injection of the PPAR-γ antagonist T0070907. CONCLUSION: EA attenuates cerebral I/R injury by regulating oxidative stress, neuronal death and neuroinflammation via stimulation of PPAR-γ.

Electroacupuncture for Spinal Cord Injury: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Background: Previous studies have shown that electroacupuncture (EA) has a positive effect on motor and sensory function in patients with spinal cord injury (SCI). This review evaluated the effectiveness of EA for improvement in activities of daily living in patients with SCI. Methods: We searched the Cochrane Library, PubMed, Web of Science, CNKI, WanFang Data, and VIP databases using a search strategy according to the guidelines of the Cochrane Handbook for Systematic Review of Interventions up to 30th September 2020. Only randomized controlled trials (RCTs) of EA in patients with SCI were included. We analyzed the data using RevMan (version 5.3) and graded the quality of evidence using GRADE profiler 3.6.1. Results: This meta-analysis included 10 RCTs with 712 patients. Three studies revealed that the functional independence measure score for SCI patients in the EA group was higher than that in the control group (mean difference [MD] = 13.46, 95% CI: 8.00 to 18.92, P < 0.00001). Five studies showed that the modified Barthel index in the EA group was higher than that in the control group (MD = 6.92, 95% CI: 4.96 to 8.89, P < 0.00001). Five studies showed that the American Spinal Injury Association-motor score (ASIA-motor score) in the EA group was higher than that in the control group (standard MD = 0.96, 95% CI: 0.75 to 1.18, P < 0.00001). Three studies reported the ASIA-tactile and pain scores and also reported that the scores in the EA group were higher than those in the control group, with high homogeneity (tactile I2 = 86%, P = 0.0008; pain I2 = 54%, P = 0.11). The quality of evidence for the use of EA for improvement in motor and sensory function in SCIs was moderate according to the GRADE system. Conclusion: This review suggested that EA improves activities of daily living and motor function in patients with SCI, with a moderate level of evidence.

Electroacupuncture promotes the survival and synaptic plasticity of hippocampal neurons and improvement of sleep deprivation-induced spatial memory impairment.

AIMS: This study aimed to investigate whether electroacupuncture (EA) promotes the survival and synaptic plasticity of hippocampal neurons by activating brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase (TrkB)/extracellular signal-regulated kinase (Erk) signaling, thereby improving spatial memory deficits in rats under SD. METHODS: In vivo, Morris water maze (MWM) was used to detect the effect of EA on learning and memory, at the same time Western blotting (WB), immunofluorescence (IF), and transmission electron microscopy (TEM) were used to explore the plasticity of hippocampal neurons and synapses, and the expression of BDNF/TrkB/Erk signaling. In vitro, cultured hippocampal neurons were treated with exogenous BDNF and the TrkB inhibitor K252a to confirm the relationship between BDNF/TrkB/Erk signaling and synaptic plasticity. RESULTS: Our results showed that EA mitigated the loss of hippocampal neurons and synapses, stimulated hippocampal neurogenesis, and improved learning and memory of rats under SD accompanied by upregulation of BDNF and increased phosphorylation of TrkB and Erk. In cultured hippocampal neurons, exogenous BDNF enhanced the expression of synaptic proteins, the frequency of the postsynaptic currents, and the phosphorylation of TrkB and Erk; these effects were reversed by treatment with K252a. CONCLUSIONS: Electroacupuncture alleviates SD-induced spatial memory impairment by promoting hippocampal neurogenesis and synaptic plasticity via activation of BDNF/TrkB/Erk signaling, which provided evidence for EA as a therapeutic strategy for countering the adverse effects of SD on cognition.

[Effect of Electroacupuncture on the Expression of Hippocampal eNSCs in MCAO Model Rats].

Objective To observe the effects of electroacupuncture (EA) on hippocampal en- dogenous neural stem cells (eNSCs) expression of middle cerebral artery occlusion (MCAO) model rats after cerebral ischemia-reperfusion (I/R) at different time points, and to observe possible mechanisms of EA for keeping away from damage in acute cerebral infarction (ACI). Methods MCAO model was pre- pared in male SPF grade SD rats by suture method. Totally 90 rats were divided into the sham-operated group, the model group, and the EA group according to random number table, 30 in each group. Rats in the sham-operated group only received surgical trauma. Rats in the model group only received MCAO I/R injury. Rats in the EA group received EA at Baihui (DU20) and Dazhui (DU14) , once per day, 30 min each time. Nerve defects of rats were tested by neural function defect scale at day 1 , 7, 14 of treatment, respectively. Meanwhile, 6 rats were executed randomly from each group. Their hippocampus tissues were isolated. Then the proliferation and differentiation expression of eNSCs in the hippocampus area were detected by immunofluorescence method. Results (1) The scores of nerve function defect scale: The scores of the model group increased at day 1, 7, 14 of treatment, being higher as compared with those of the sham-operated group (P <0. 05). The scores of the EA group were lower than those of the model group at day 1, 7, 14 of treatment (P <0. 05). (2) The expression of BrdU positive cells: Com- pared with the sham-operated group, the expression of BrdU positive cells in the model group were in- creased at day 1, 7, 14 of treatment (P <0. 05). Compared with the model group at each time points, the expression of BrdU positive cells in the EA group were increased more at day 1, 7, 14 of treatment (P < 0. 05). (3) The expression of Nestin positive cells: The expression of Nestin positive cells were in- creased more in the model group than in the sham-operated group at day 1 , 7, 14 of treatment (P < 0. 05). Compared with the model group, the expression of Nestin positive cells increased more in the EA group, but only with statistical difference at day 7 of treatment (P <0. 05). (4) the expression of DCX positive cells: the expression of DCX positive cells were increased more in the model group than in the sham-operated group at day 1 and 7 of treatment (P <0. 05). Compared with the model group, the ex- pression of DCX positive cells were increased more in the EA group at day 7 and 14 of treatment (P < 0. 05). (5) the expression of NeuN positive cells: The expression NeuN of positive cells were increased more in the model group than in the sham-operated group at day 1, 7, and 14 of treatment, but only with statistical difference at day 14 of treatment (P <0. 05). Compared with the model group, the expression of NeuN positive cells were increased more obviously, but only with statistical difference at day 1 and 14 of treatment (P <0.05). (6) the expression of GFAP positive cells: The expression of GFAP positive cells increased more obviously in the model group than in the sham-operated group at day 1 , 7, and 14 of treatment (P <0. 05). Compared with the model group, the expression of GFAP positive cells were not obviously increased in the EA group, but only with statistical difference at day 14 of treatment (P <0. 05). Conclusions The proliferation and differentiation of eNSCs exist in the hippocampus area after cerebral I/R in MCAO model rats. EA could improve the recovery of damaged nerve function. Its possible mecha- nism might lie in that EA could promote the proliferation and differentiation of eNSCs in hippocampus area, inhibit excessive differentiation of eNSCs into astrocytes , promote differentiation of eNSCs into neu- rons, and improve regeneration of nerve cells.