Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

BMC Neurosci. 2012 Sep 19:13:111. doi: 10.1186/1471-2202-13-111.

Abstract

Background: Electroacupuncture (EA) pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling.

Results: EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment.

Conclusions: EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Brain Infarction / drug therapy
  • Brain Infarction / etiology
  • Brain Infarction / prevention & control
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Electroacupuncture*
  • Enzyme Inhibitors / adverse effects
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism*
  • Infarction, Middle Cerebral Artery / prevention & control*
  • Male
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / etiology
  • Nervous System Diseases / prevention & control
  • Peptides / adverse effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Reperfusion
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Signal Transduction / radiation effects
  • Time Factors
  • Transcription Factor HES-1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Enzyme Inhibitors
  • Hes1 protein, rat
  • Homeodomain Proteins
  • MW167
  • Peptides
  • RNA, Messenger
  • Receptors, Notch
  • Transcription Factor HES-1