title: Electroacupuncture-like stimulation at Baihui and Dazhui acupoints exerts neuroprotective effects through activation of the brain-derived neurotrophic factor-mediated MEK1/2/ERK1/2/p90RSK/bad signaling pathway in mild transient focal cerebral ischemia in rats.
abstract: BACKGROUND
  This study was designed to evaluate the effects of electroacupuncture-like stimulation at Baihui (GV20) and Dazhui (GV14) acupoints (EA at acupoints) following mild cerebral ischemia-reperfusion (I/R) injury. Furthermore, we investigated whether brain-derived neurotrophic factor (BDNF)-mediated activation of extracellular signal-regulated kinase (ERK)1/2 signaling pathway is involved in the neuroprotection induced by EA at acupoints.
  
  
  METHODS
  Rats were 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 once daily for 2 consecutive days.
  
  
  RESULTS
  Following the application of EA at acupoints, initiated 1 d postreperfusion, we observed significant reductions in the cerebral infarct area, neurological deficit scores, active caspase-3 protein expression, and apoptosis in the ischemic cortex 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 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 after 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 did not influence BDNF and pRaf-1 expression.
  
  
  CONCLUSIONS
  Overall, our study results indicated that EA at acupoints, initiated 1 d postreperfusion, upregulates BDNF expression to provide BDNF-mediated neuroprotection against caspase-3-dependent neuronal apoptosis through activation of the Raf-1/MEK1/2/ERK1/2/p90RSK/Bad signaling cascade after 3 d of reperfusion in mild MCAo.
authors.forename: Chin Yi
authors.initials: CY
authors.lastname: Cheng
authors.forename: Jaung Geng
authors.initials: JG
authors.lastname: Lin
authors.forename: Shan Yu
authors.initials: SY
authors.lastname: Su
authors.forename: Nou Ying
authors.initials: NY
authors.lastname: Tang
authors.forename: Shung Te
authors.initials: ST
authors.lastname: Kao
authors.affiliation: Acupuncture Research Center, China Medical University, Taichung 40402, Taiwan. clhsieh@mail.cmuh.org.tw.
authors.forename: Ching Liang
authors.initials: CL
authors.lastname: Hsieh
mesh_terms: D015669:Acupuncture Points; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D015671:Electroacupuncture; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000628:therapy*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases