title: Electroacupuncture-like stimulation at the Baihui (GV20) and Dazhui (GV14) acupoints protects rats against subacute-phase cerebral ischemia-reperfusion injuries by reducing S100B-mediated neurotoxicity.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the effects of electroacupuncture-like stimulation at the Baihui (GV20) and Dazhui (GV14) acupoints (EA at acupoints) during the subacute phase of cerebral ischemia-reperfusion (I/R) injury and to establish the neuroprotective mechanisms involved in the modulation of the S100B-mediated signaling pathway.
  
  
  METHODS
  The experimental rats were subjected to middle cerebral artery occlusion (MCAo) for 15 min followed by 1 d or 7 d of reperfusion. EA at acupoints was applied 1 d postreperfusion then once daily for 6 consecutive days.
  
  
  RESULTS
  We observed that 15 min of MCAo caused delayed infarct expansion 7 d after reperfusion. EA at acupoints significantly reduced the cerebral infarct and neurological deficit scores. EA at acupoints also downregulated the expression of the glial fibrillary acidic protein (GFAP), S100B, nuclear factor-κB (NF-κB; p50), and tumor necrosis factor-α (TNF-α), and reduced the level of inducible nitric oxide synthase (iNOS) and apoptosis in the ischemic cortical penumbra 7 d after reperfusion. Western blot analysis showed that EA at acupoints significantly downregulated the cytosolic expression of phospho-p38 MAP kinase (p-p38 MAP kinase), tumor necrosis factor receptor type 1-associated death domain (TRADD), Fas-associated death domain (FADD), cleaved caspase-8, and cleaved caspase-3 in the ischemic cortical penumbra 7 d after reperfusion. EA at acupoints significantly reduced the numbers of GFAP/S100B and S100B/nitrotyrosine double-labeled cells.
  
  
  CONCLUSIONS
  Our study results indicate that EA at acupoints initiated 1 d postreperfusion effectively downregulates astrocytic S100B expression to provide neuroprotection against delayed infarct expansion by modulating p38 MAP kinase-mediated NF-κB expression. These effects subsequently reduce oxidative/nitrative stress and inhibit the TNF-α/TRADD/FADD/cleaved caspase-8/cleaved caspase-3 apoptotic pathway in the ischemic cortical penumbra 7 d after reperfusion.
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Chinese Medicine, Hui-Sheng Hospital, Taichung, Taiwan.
authors.forename: Chin-Yi
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Jaung-Geng
authors.initials: JG
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Nou-Ying
authors.initials: NY
authors.lastname: Tang
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Shung-Te
authors.initials: ST
authors.lastname: Kao
authors.affiliation: Acupuncture Research Center, China Medical University, Taichung, Taiwan; Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Hsieh
mesh_terms: D015669:Acupuncture Points; D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000473:pathology*; D003600:Cytosol / Q000378:metabolism; D015671:Electroacupuncture; D004566:Electrodes; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism*; D013997:Time Factors
chemical_list: D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat