title: Intermittent hypoxia after transient focal ischemia induces hippocampal neurogenesis and c-Fos expression and reverses spatial memory deficits in rats.
abstract: BACKGROUND
  Memory impairment is a frequent complication of brain ischemia. Neurogenesis is implicated in learning and memory and is regulated by the transcription factor c-Fos. Preconditioning intermittent hypoxia (IH) attenuates ischemia-related memory impairments, but it is not known whether post-ischemia IH intervention has a similar effect. We investigated the effects of post-ischemia IH on hippocampal neurogenesis and c-Fos expression as well as spatial learning and memory in rats.
  
  
  RESULTS
  Focal cerebral ischemia was induced in some rats by middle cerebral artery occlusion (MCAO), while other rats received sham MCAO surgery. Beginning a week later, half of the rats of each group received IH interventions (12% oxygen concentration, 4 hrs/d, for 7 d) and half received sham IH sessions. An additional group of rats received MCAO, IH, and injections of the neurogenesis-impairing agent 3'-AZT. Spatial learning and memory was measured in the Morris water maze, and hippocampal neurogenesis and c-Fos expression were examined. Hypoxia-inducible factor 1α (HIF-1α) and phosphorylated mitogen-activated protein kinase (pMAPK) were considered as possible mediators of IH-induced changes in neurogenesis and c-Fos expression. IH intervention following MCAO resulted in recovered spatial memory, increased hippocampal neurogenesis, and increased expression of c-Fos in newborn hippocampal cells. These effects were blocked by 3'-AZT. IH intervention following MCAO also was associated with increased hippocampal pMAPK and HIF-1α expression.
  
  
  CONCLUSIONS
  IH intervention following MCAO rescued ischemia-induced spatial learning and memory impairments, likely by inducing hippocampal neurogenesis and c-Fos expression through mediators including pMAPK and HIF-1α.
authors: Department and Institute of Physical Therapy and Assistive Technology, National Yang-Ming University, Taipei, Taiwan.
authors: Yi-Wei
authors: YW
authors: Tsai
authors: Yea-Ru
authors: YR
authors: Yang
authors: Paulus S
authors: PS
authors: Wang
authors: Ray-Yau
authors: RY
authors: Wang
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000166:cytology*; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007858:Learning; D008569:Memory Disorders / Q000517:prevention & control*; D020928:Mitogen-Activated Protein Kinases; D055495:Neurogenesis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016760:Proto-Oncogene Proteins c-fos; D020928:Mitogen-Activated Protein Kinases