title: Electroacupuncture at different frequencies (5Hz and 25Hz) ameliorates cerebral ischemia-reperfusion injury in rats: possible involvement of p38 MAPK-mediated anti-apoptotic signaling pathways.
abstract: BACKGROUND
  This study aimed to determine the effects of electroacupuncture stimulation at the Baihui (GV20) and Fengfu (GV16) acupoints, at frequencies of 5Hz (EA-5Hz) and 25Hz (EA-25Hz), 7 days after cerebral ischemia-reperfusion (I/R) injury, and to evaluate the possible signaling mechanisms involved in mitogen-activated protein kinase (MAPK) pathways.
  
  
  METHODS
  Rats were subjected to 30 min of middle cerebral artery occlusion (MCAo) followed by 7 days of reperfusion. EA-5Hz or EA-25Hz was applied immediately after MCAo and then once daily for 7 consecutive days.
  
  
  RESULTS
  Results indicated that EA-5Hz and EA-25Hz both markedly attenuated cerebral infarction and neurological deficits. EA-5Hz and EA-25Hz both markedly downregulated cytosolic glial fibrillary acidic protein (GFAP), mitochondrial Bax, mitochondrial and cytosolic second mitochondrial-derived activator of caspase/direct inhibitor of apoptosis protein-binding protein with low isoelectric point (Smac/DIABLO), and cytosolic cleaved caspase-3 expression, and effectively restored cytosolic phospho-p38 MAPK (p-p38 MAPK), cytosolic cAMP response element-binding protein (CREB), mitochondrial Bcl-xL, and cytosolic X-linked inhibitor of apoptosis protein (XIAP) expression, in the ischemic cortical penumbra 7 days after reperfusion. Both EA-5Hz and EA-25Hz also significantly increased the ratios of mitochondrial Bcl-xL/Bax and Bcl-2/Bax, respectively.
  
  
  CONCLUSIONS
  Both EA-5Hz and EA-25Hz effectively downregulate reactive astrocytosis to provide neuroprotection against cerebral infarction, most likely by activating the p38 MAPK/CREB signaling pathway. The modulating effects of EA-5Hz and EA-25Hz on Bax-mediated apoptosis are possibly due to the activation of p38 MAPK/CREB/Bcl-xL and p38 MAPK/CREB/Bcl-2 signaling pathways, respectively, and eventually contribute to the prevention of Smac/DIABLO translocation and subsequent restoration of XIAP-mediated suppression of caspase-3 in the cortical periinfarct area 7 days after reperfusion.
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. c5398@ms22.hinet.net.|Department of Chinese Medicine, Hui-Sheng Hospital, 42056, Taichung, Taiwan. c5398@ms22.hinet.net.
authors.forename: Chin-Yi
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. jglin@mail.cmu.edu.tw.
authors.forename: Jaung-Geng
authors.initials: JG
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. nouing@mail.cmu.edu.tw.
authors.forename: Nou-Ying
authors.initials: NY
authors.lastname: Tang
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. stkao@mail.cmu.edu.tw.
authors.forename: Shung-Te
authors.initials: ST
authors.lastname: Kao
authors.affiliation: Department of Chinese Medicine, China Medical University Hospital, 40447, Taichung, Taiwan. clhsieh@mail.cmuh.org.tw.|Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan. clhsieh@mail.cmuh.org.tw.|Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung, 40402, Taiwan. clhsieh@mail.cmuh.org.tw.
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D015671:Electroacupuncture / Q000379:methods*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction / Q000528:radiation effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases