title: Neuroprotective effects of electroacupuncture on hypoxic-ischemic encephalopathy in newborn rats are associated with increased expression of GDNF-RET and protein kinase B.
abstract: OBJECTIVE
  To explore the neuroprotective effects of electroacupuncture (EA) on hypoxic-ischemic encephalopathy (HIE) and to further investigate the role of glial cell line-derived neurotrophic factor (GDNF) family receptor member RET (rearranged during transfection) and its key downstream phosphatidylinositol 3 kinase (PI-3K)/protein kinase B (Akt) pathway in the process.
  
  
  METHODS
  A total of 220 seven-day-old SD rats (of either sex, from 22 broods) were randomly divided into two groups, one (30 rats) for sham-surgery group and the other (190 rats) for HIE model group. The HIE model was established using the left common carotid artery ligation method in combination with hypoxic treatment. The successfully established rats were randomly divided into five groups, including control model group, EA group, sham-EA group, antagonist group and antagonist plus electroacupuncture group, with 35 rats in each group. Baihui (GV 20), Dazhui (GV 14), Quchi (LI 11) and Yongquan (KI 1) acupoints were chosen for acupuncture. EA was performed at Baihui and Quchi for 10 min once a day for continuous 1, 3, 7 and 21 days, respectively. The rats were then killed after the operation and injured cerebral cortex was taken for the measurement of neurologic damage by hematoxylin-eosin (HE) staining and the degenerative changes of cortical ultrastructure by transmission electron microscopy. RET mRNA level and Akt protein level were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively.
  
  
  RESULTS
  EA could ameliorate neurologic damage of the first somatic sensory area (S1Tr) and alleviate the degenerative changes of ultrastructure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex.
  
  
  CONCLUSIONS
  EA has neuroprotective effects on HIE and could be a potential therapeutic strategy for HIE in the neonate. Activation of RET/Akt signaling pathway might be involved in this process.
authors.affiliation: Traditional Chinese Medicine Department, Qingdao Women and Children Hospital, Qingdao, Shandong Province, 266013, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: College of Acupuncture and Moxibustion and Massage, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China. ngxu@tom.cn.
authors.forename: Neng-Gui
authors.initials: NG
authors.lastname: Xu
authors.affiliation: College of Acupuncture and Moxibustion and Massage, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: Traditional Chinese Medicine Department, Qingdao Women and Children Hospital, Qingdao, Shandong Province, 266013, China.
authors.forename: Yan-Zhen
authors.initials: YZ
authors.lastname: Wan
authors.affiliation: College of Acupuncture and Moxibustion and Massage, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Wu
authors.affiliation: College of Acupuncture and Moxibustion and Massage, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Kang-Bai
authors.initials: KB
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000473:pathology / Q000648:ultrastructure; D015671:Electroacupuncture; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D051057:Proto-Oncogene Proteins c-akt
keywords: electroacupuncture; glial cell line-derived neurotrophic factor; hypoxic-ischemic encephalopathy; protein kinase B; rearranged during transfection