Nsduction pathways: the phosphatidylinositol 3-kinase (PI3K) as well as the mitogen-activated protein kinase (MAPK) pathways [10]. Koh identified that the MAPK/extracellular signal-regulated kinase (ERK)1/2 signaling pathway can be a essential mediator of neuronal cell survival against apoptosis in a focal cerebral ischemia model in rats [11]. Many research have shown that BDNF delivers neuroprotective effects against apoptotic cell death through the stimulation of a protein kinase cascade that consists of the sequential activation of Raf-1, MAPK/ERK kinase1/2 (MEK1/2), and ERK1/2 [12,13]. Extracellular signal-regulated kinase1/2 then phosphorylates the 90 kDa ribosomal S6 kinase (p90RSK), major for the phosphorylation of Poor and also the attenuation of caspase-3-dependent apoptosis [14,15]. In prior research, BDNF agonists improved neurological function and reduced infarct size inside a transient focal cerebral ischemia model in rats [16,17]. However, MEK/ERK inhibitors abrogated BDNF-induced neuroprotection in hippocampal neurons in vitro [6] and in neonatal hypoxic-ischemic brain injury in vivo [18]. Chinese physicians have made use of acupuncture to treat numerous disorders for a number of centuries [19]. In accordance with standard Chinese medicine, Baihui (GV20) and Dazhui (GV14) are both acupoints around the “Du meridian”, which travels in to the brain, and are usually made use of to treat stroke. Experimental research in rats have shown that EA stimulation at acupoints (which include Baihui and Shuigou acupoints) can attenuate cerebral infarction and improve neurological outcome following transient middle cerebral artery occlusion (MCAo) [20,21].227454-58-2 Data Sheet Kim et al. have reported that pretreatment with EA at Baihui and Dazhui acupoints elicit neuroprotection by means of increased BDNF and stromal cell derived factor-1 (SDF-1) expression 1 d right after MCAo [22]. Other studies have also shown thatEA can potentially deliver neuroprotection against cerebral ischemic insults by means of activation of many survival signaling pathways [20,23-25].4-Oxotetrahydrofuran-3-carbonitrile Chemical name However, the detailed mechanisms underlying BDNF-induced neuroprotection resulting from EA stimulation at Baihui and Dazhui acupoints following mild cerebral I/R injury stay unclear.PMID:24732841 The aim of this study was, as a result, to evaluate the effects of EA-like stimulation at Baihui and Dazhui acupoints (EA at acupoints) right after 15 min of ischemia followed by 3 d of reperfusion, and to elucidate the mechanisms involved inside the BDNF-mediated signaling transduction pathway.MethodsExperimental animalsMale Sprague Dawley (SD) rats weighing 300 g to 350 g have been employed. This study was reviewed and authorized by China Medical University Institutional Animal Care and Use Committee (Permit Quantity: 100-215-c), plus the committee recognized that the proposed experimental procedures compiled with all the Animal Protection Law by the Council of Agriculture, Executive Yuan, Taiwan. All of the procedures with animals avoided or minimized discomfort, distress, and pain towards the animals.The MCAo modelThe MCAo model was established inside the SD rats applying an intraluminal suture approach as described previously [26]. Briefly, the rats have been anesthetized with chloral hydrate (400 mg/kg, intraperitoneally), and also the ideal common carotid artery (CCA) and internal carotid artery (ICA) had been exposed by way of an incision within the midline neck before ligation in the pterygopalatine artery close to its branch. A 3? nylon filament suture, blunted at the tip by a flame and coated with poly-L-lysine (Sigma, USA), was in.