Activation of extracellular signal-regulated kinase (ERK)1/2 signaling pathway is involved in the neuroprotection induced by EA at acupoints. Strategies: Rats had been subjected to middle cerebral artery occlusion (MCAo) for 15 min followed by reperfusion for 3 d. EA at acupoints was applied 1 d postreperfusion then after every day for two consecutive days. Results: Following the application of EA at acupoints, initiated 1 d postreperfusion, we observed considerable reductions inside the cerebral infarct location, neurological deficit scores, active caspase-3 protein expression, and apoptosis inside the ischemic cortex immediately after 3 d of reperfusion. We also observed markedly upregulated BDNF, phospho-Raf-1 (pRaf-1), phospho-MEK1/2 (pMEK1/2), phospho-ERK1/2 (pERK1/2), phospho-90 kDa ribosomal S6 kinase (pp90RSK), and phospho-Bad (pBad) expression, and restored neuronal nuclear antigen (NeuN) expression. Pretreatment together with the MEK1/2 inhibitor U0126 abrogated the effects of EA at acupoints on cerebral infarct size, neurological deficits, active caspase-3 protein, and apoptosis in the ischemic cortex following 3 d of reperfusion. Pretreatment with U0126 also abrogated the effects of EA at acupoints on pMEK1/2, pERK1/2, pp90RSK, pBad, and NeuN expression, but didn’t influence BDNF and pRaf-1 expression. Conclusion: Overall, our study final results indicated that EA at acupoints, initiated 1 d postreperfusion, upregulates BDNF expression to provide BDNF-mediated neuroprotection against caspase-3-dependent neuronal apoptosis via activation of your Raf-1/MEK1/2/ERK1/2/p90RSK/Bad signaling cascade just after three d of reperfusion in mild MCAo. Key phrases: Electroacupuncture, Brain-derived neurotrophic aspect, Phospho-ERK1/2, Phospho-p90RSK, Phospho-Bad, Apoptosis* Correspondence: [email protected] three Acupuncture Analysis Center, China Health-related University, Taichung 40402, Taiwan 4 Division of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan Complete list of author data is offered at the end of the article?2014 Cheng et al.; licensee BioMed Central Ltd. This can be an Open Access article distributed beneath the terms with the Creative Commons Attribution License (http://creativecommons.Azido-PEG8-acid Formula org/licenses/by/2.625120-14-1 Purity 0), which permits unrestricted use, distribution, and reproduction in any medium, offered the original function is appropriately credited.Cheng et al. BMC Complementary and Option Medicine 2014, 14:92 http://biomedcentral/1472-6882/14/Page two ofBackground Cerebral ischemia-reperfusion (I/R) injury produces big amounts of reactive oxygen species, which initiate a series of cellular events and that result in necrosis and apoptosis [1]. In mild transient focal cerebral ischemia, brain infarction can develop and progress in a delayed manner, and turn out to be grossly visible just after 3 d of reperfusion [2,3].PMID:23776646 Apoptosis, that is dependent on caspase-3 activation, plays a substantial part in the pathology with the delayed infarction and predominates in ischemic neurons in the course of mild focal cerebral ischemia [2-4]. Neurotrophic things supply neuroprotection against caspase-3-dependent apoptosis by activating numerous signal transduction pathways following cerebral I/R injury [5,6]. Brain-derived neurotrophic issue (BDNF) can be a member with the neurotrophin loved ones that plays a vital function in neuroplasticity, neuron improvement, differentiation, and neuronal survival [7-9]. It binds towards the distinct tyrosine kinase B (TrkB) receptor on neurons to activate two important intracellular signal tra.