title: Hypoxia inducible factor-1α expression is associated with hippocampal apoptosis during epileptogenesis.
abstract: Cell apoptosis can cause hippocampal neuronal loss after epileptic seizures. Hypoxia inducible factor (HIF)-1α is an important factor mediating apoptosis after brain injuries, such as cerebral ischemia and traumatic brain injures, but little research has been done on its role in the lithium chloride-pilocarpine induced epileptic model. Here, we used a rat model of pilocarpine-induced status epilepticus (SE) to investigate HIF-1α expression and apoptosis in the hippocampus, and to explore their relationship during epileptogenesis. 120 male Sprague Dawley (SD) rats were treated with lithium chloride-pilocarpine injections and divided into an experimental group (administered by MK-801) and a positive control group (administered by saline). Then the HIF-1α expression and hippocampal apoptosis were investigated by histological confirmation and western blotting at 24h, 3d, 7d and 14d, respectively. The results showed that the administration of MK-801 significantly reduced (P<0.05) HIF-1α expression and hippocampal apoptosis during epileptogenesis in comparison with the positive control. Moreover, the expression of HIF-1α and hippocampal apoptosis presented significant time-dependent changes (P<0.01) within 2 weeks, and their positive correlation (P<0.05) analyzed by Pearson׳s correlation analysis. Meanwhile, the HIF-1α immunostained cells were distributed in accord with TUNEL immunostained cells and Caspase-3 immunopositive cells in the hippocampus. These results indicate that the HIF-1α expression is associated with hippocampal apoptosis, and suggest that HIF-1α is an important factor during epileptogenesis.
authors.affiliation: Department of Neurosurgery, The Central Hospital of Xi׳an, Affiliated Hospital of Medical College of Xi׳an Jiao Tong University, No. 185 Houzai Gate of North Street, Xi׳an 710003, China.
authors.forename: Qianfa
authors.initials: Q
authors.lastname: Long
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.17 Changle West Road, Xi׳an 710032, China.
authors.forename: Cairui
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.17 Changle West Road, Xi׳an 710032, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Kai
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.17 Changle West Road, Xi׳an 710032, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, The Central Hospital of Xi׳an, Affiliated Hospital of Medical College of Xi׳an Jiao Tong University, No. 185 Houzai Gate of North Street, Xi׳an 710003, China.
authors.forename: Weichuan
authors.initials: W
authors.lastname: Xin
authors.affiliation: Department of Neurosurgery, The Central Hospital of Xi׳an, Affiliated Hospital of Medical College of Xi׳an Jiao Tong University, No. 185 Houzai Gate of North Street, Xi׳an 710003, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Central Hospital of Xi׳an, Affiliated Hospital of Medical College of Xi׳an Jiao Tong University, No. 185 Houzai Gate of North Street, Xi׳an 710003, China.
authors.forename: Ansheng
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Central Hospital of Xi׳an, Affiliated Hospital of Medical College of Xi׳an Jiao Tong University, No. 185 Houzai Gate of North Street, Xi׳an 710003, China.
authors.forename: Zhanyao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Armed Police Hospital of Shaanxi Province, No. 88 East Part of Second South Ring Road, Xi׳an 710054, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.17 Changle West Road, Xi׳an 710032, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
authors.affiliation: Department of Radiology, University of Washington School of Medicine, Box 357115, Seattle, WA 98195, USA. Electronic address: bqiu@u.washington.edu.
authors.forename: Bensheng
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.17 Changle West Road, Xi׳an 710032, China. Electronic address: liuwp@fmmu.edu.cn.
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D003292:Convulsants; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D018021:Lithium Chloride; D008297:Male; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010862:Pilocarpine; D016291:Dizocilpine Maleate; D018021:Lithium Chloride
keywords: Apoptosis; Epilepsy; Hippocampus; Hypoxia inducible factor-1α