title: CXCR4 Antagonist AMD3100 Suppresses the Long-Term Abnormal Structural Changes of Newborn Neurons in the Intraventricular Kainic Acid Model of Epilepsy.
abstract: Abnormal hippocampal neurogenesis is a prominent feature of temporal lobe epilepsy (TLE) models, which is thought to contribute to abnormal brain activity. Stromal cell-derived factor-1 (SDF-1) and its specific receptor CXCR4 play important roles in adult neurogenesis. We investigated whether treatment with the CXCR4 antagonist AMD3100 suppressed aberrant hippocampal neurogenesis, as well as the long-term consequences in the intracerebroventricular kainic acid (ICVKA) model of epilepsy. Adult male rats were randomly assigned as control rats, rats subjected to status epilepticus (SE), and post-SE rats treated with AMD3100. Animals in each group were divided into two subgroups (acute stage and chronic stage). We used immunofluorescence staining of BrdU and DCX to analyze the hippocampal neurogenesis on post-SE days 10 or 74. Nissl staining and Timm staining were used to evaluate hippocampal damage and mossy fiber sprouting, respectively. On post-SE day 72, the frequency and mean duration of spontaneous seizures were measured by electroencephalography (EEG). Cognitive function was evaluated by Morris water maze testing on post-SE day 68. The ICVKA model of TLE resulted in aberrant neurogenesis such as altered proliferation, abnormal dendrite development of newborn neurons, as well as spontaneous seizures and spatial learning impairments. More importantly, AMD3100 treatment reversed the aberrant neurogenesis seen after TLE, which was accompanied by decreased long-term seizure activity, though improvement in spatial learning was not seen. AMD3100 could suppress long-term seizure activity and alter adult neurogenesis in the ICVKA model of TLE, which provided morphological evidences that AMD3100 might be beneficial for treating chronic epilepsy.
authors: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.|Department of Neurology, Benxi Central Hospital of China Medical University, Benxi, Liaoning, People's Republic of China.
authors: Chengguang
authors: C
authors: Song
authors: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.
authors: Wangshu
authors: W
authors: Xu
authors: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.
authors: Xiaoqian
authors: X
authors: Zhang
authors: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.
authors: Shang
authors: S
authors: Wang
authors: Department of Psychiatry, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, People's Republic of China.
authors: Gang
authors: G
authors: Zhu
authors: Department of Dermatology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, People's Republic of China.|Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, Liaoning, People's Republic of China.
authors: Ting
authors: T
authors: Xiao
authors: Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang, Liaoning, People's Republic of China.
authors: Mei
authors: M
authors: Zhao
authors: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China. cszhao@mail.cmu.edu.cn.
authors: Chuansheng
authors: C
authors: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001596:Benzylamines; D000080027:Cyclams; D003712:Dendrites / Q000187:drug effects / Q000648:ultrastructure; D000089662:Doublecortin Protein; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D057967:Infusions, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects*; D011897:Random Allocation; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
chemical_list: D001596:Benzylamines; C486264:Cxcr4 protein, rat; D000080027:Cyclams; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor; D007608:Kainic Acid
keywords: Basal dendrite; Neurogenesis; Stromal cell-derived factor-1; Temporal lobe epilepsy
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