Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (6): 1079-1085.doi: 10.4103/1673-5374.270416

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

Bing-Chao Dong1 , Mei-Xuan Li1 , Xiao-Yin Wang1 , Xi Cheng 1 , Yu Wang 1 , Ting Xiao2 , Jukka Jolkkonen3 , Chuan-Sheng Zhao1 , Shan-Shan Zhao1   

  1. 1 Department of Neurology, Te First Hospital of China Medical University, Shenyang, Liaoning Province, China
    2 Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, Liaoning Province, China 
    3 Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
  • Online:2020-06-15 Published:2020-07-02
  • Contact: Shan-Shan Zhao, MD,zhaoshsh826@hotmail.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81401002 (to SSZ).

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Abstract: 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 efects of CXCR7, a new atypical receptor of stromal cell-derived factor-1, on hippocampal neurogenesis afer a stroke remain largely unknown. Our study is the frst to investigate the efect 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. Te 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 in- jection. Both sham and ischemic rats were treated with intraventricular infusions of CXCR7-neutralizing antibodies for 6 days 1 week afer surgery. Immunofuorescence 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-la- beled 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 afer ischemia. CXCR7-neutralizing antibody treatment signifcantly 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. Tese results suggest that CXCR7-neutralizing antibody enhances the neurogenesis in the dentate gyrus and improves the cognitive function afer cerebral ischemia in rats. All animal experimental protocols and procedures were approved by the Institutional Animal Care and Use Committee of China Medical University (CMU16089R) on December 8, 2016.

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