Effects of CXCR7-neutralizing antibody on neurogenesis in the hippocampal dentate gyrus and cognitive function in the chronic phase of cerebral ischemia

作     者：Bing-Chao Dong Mei-Xuan Li Xiao-Yin Wang Xi Cheng Yu Wang Ting Xiao Jukka Jolkkonen Chuan-Sheng Zhao Shan-Shan Zhao Bing-Chao Dong;Mei-Xuan Li;Xiao-Yin Wang;Xi Cheng;Yu Wang;Ting Xiao;Jukka Jolkkonen;Chuan-Sheng Zhao;Shan-Shan Zhao

作者机构：Department of NeurologyThe First Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Key Laboratory of ImmunodermatologyMinistry of HealthMinistry of EducationShenyangLiaoning ProvinceChina Department of NeurologyInstitute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2020年第15卷第6期

页      面：1079-1085页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China No.81401002(to SSZ) 

主　　题：cerebral ischemia cognitive function CXCR7 dendritic development dentate gyrus doublecortin neurogenesis neutralizing antibody stroke stromal cell-derived factor-1 

摘      要：Stromal cell-derived factor-1 and its receptor CXCR4 are essential regulators of the neurogenesis that occurs in the adult hippocampal dentate gyrus.However,the effects of CXCR7,a new atypical receptor of stromal cell-derived factor-1,on hippocampal neurogenesis after a stroke remain largely unknown.Our study is the first to investigate the effect of a CXCR7-neutralizing antibody on neurogenesis in the dentate gyrus and the associated recovery of cognitive function of rats in the chronic stage of cerebral ischemia.The rats were randomly divided into sham,sham+anti-CXCR7,ischemia and ischemia+anti-CXCR7 groups.Endothelin-1 was injected in the ipsilateral motor cortex and striatum to induce focal cerebral ischemia.Sham group rats were injected with saline instead of endothelin-1 via intracranial injection.Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week after surgery.Immunofluorescence staining with doublecortin,a marker for neuronal precursors,was performed to assess the neurogenesis in the dentate gyrus.We found that anti-CXCR7 antibody infusion enhanced the proliferation and dendritic development of doublecortin-labeled cells in the dentate gyrus in both ischemic and sham-operated rats.Spatial learning and memory functions were assessed by Morris water maze tests 30-32 days after ischemia.CXCR7-neutralizing antibody treatment significantly reduced the escape latency of the spatial navigation trial and increased the time spent in the target quadrant of spatial probe trial in animals that received ischemic insult,but not in sham operated rats.These results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function after cerebral ischemia in rats.All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University(CMU16089 R)on December 8,2016.