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In some regions of the hippocampus, neurogenesis persists throughout life and is upregulated following hypoxia/ischemia. The mechanisms underlying the upregulation of neurogenesis, however, are not known. Here we examined the expression of two factors thought to be involved in hypoxia-related neurogenesis, hypoxia-inducible factor-1α (HIF-1α) and brain-derived erythropoietin (EPO), in the hippocampus of neonatal rats following hypoxia-ischemia. Sprague-Dawley rat pups were exposed to hypoxia-ischemia conditions or hypoxia conditions only. For the hypoxia-ischemia experiment, the left common carotid artery of Sprague-Dawley rat pups was ligated on postnatal day 7. The pups were exposed to hypoxic conditions and then returned to normoxia for re-oxygenation. Immunohistochemical staining was performed to evaluate EPO and HIF-1α expression at various time points after re-oxygenation (1 h, 6 h, 16 h, 1 d, 3 d, and 7 d). EPO expression in the hippocampus was verified using Western blot studies. For the hypoxia-only experiment, postnatal day 7 rat pups were continuously exposed to hypoxic conditions for different durations (0.5 h, 1 h, 2 h, 3 h, and 5 h). HIF-1α expression in the hippocampus was evaluated by immunohistochemical staining. In the hypoxia-ischemia group, EPO expression was significantly altered. The EPO expression increased during re-oxygenation, peaked at 16 h, and decreased thereafter. In the hypoxia-only group, the EPO protein was not detectable. When the rat pups were returned to normoxia for re-oxygenation, there was no HIF-1α expression. HIF-1α immunoreactivity was present in the hypoxia-only group and peaked in rats exposed to continuous hypoxic conditions for 3 h. In addition, endogenous EPO increased in the neonatal rats after the hypoxia-ischemia event. Furthermore, HIF-1α was induced as a result of hypoxia. We postulate that disruption of homeostasis triggers and enhances hippocampal neurogenesis. Thus, HIF-1α/EPO hypoxic signal transduction may initiate hippocampal neurogenesis following hypoxia-ischemia.
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
September 2009,
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
December 2011,
Journal of Korean Neurosurgical Society,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
October 2014,
Neuroreport,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
December 2007,
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
March 2017,
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
January 2013,
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
December 2012,
Pediatric blood & cancer,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
May 2019,
Journal of cellular biochemistry,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
August 2015,
Journal of ethnopharmacology,
Junjie Lu, and
Li Jiang, and
Huan Zhu, and
Long Zhang, and
Ting Wang
January 2013,
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