title: CXCR4 antagonist AMD3100 reverses the neurogenesis and behavioral recovery promoted by forced limb-use in stroke rats.
abstract: OBJECTIVE
  Forced limb-use can enhance neurogenesis and behavioral recovery as well as increasing the level of stromal cell-derived factor-1 (SDF-1) in stroke rats. We examined whether the SDF-1/CXCR4 pathway is involved in the enhanced neurogenesis and promoted behavioral recovery induced by forced limb-use in the chronic phase of stroke.
  
  
  METHODS
  The CXCR4 antagonist, AMD3100, was used to block the SDF-1/CXCR4 pathway in the ischemic rats. Brain ischemia was induced by endothelin-1. One week after ischemia, the unimpaired forelimb of rats was immobilized for 3 weeks. The proliferation, migration, and survival of DCX-positive cells in the subventricular zone (SVZ), and the dendritic complexity of DCX-positive cells in the dentate gyrus (DG), as well as the inflammatory response in the infarcted striatum were analyzed by immunohistochemistry. Functional recovery was assessed in beam-walking and water maze tests.
  
  
  RESULTS
  Forced limb-use enhanced the proliferation, migration, dendritic complexity and the survival of newborn neurons. Furthermore, forced limb-use suppressed the inflammatory response and improved both motor and cognitive functions after stroke. AMD3100 significantly abrogated the enhanced neurogenesis and behavioral recovery induced by forced limb-use without influencing the inflammatory response.
  
  
  CONCLUSIONS
  SDF-1/CXCR4 pathway seems to be involved in the enhancement of neurogenesis and behavioral recovery induced by post-stroke forced limb-use.
authors.affiliation: Department of Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Qu
authors.affiliation: Department of Obstetrics, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, The First Hospital of China Medical University, Shenyang, China.|Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
authors.affiliation: Department of Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001596:Benzylamines; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation; D002491:Central Nervous System Agents / Q000494:pharmacology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D000080027:Cyclams; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D019332:Endothelin-1; D005552:Forelimb / Q000187:drug effects / Q000503:physiopathology; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007103:Immobilization / Q000379:methods / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D026201:Musculoskeletal Manipulations / Q000379:methods; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D020521:Stroke / Q000473:pathology / Q000503:physiopathology; D000071939:Stroke Rehabilitation
chemical_list: D001596:Benzylamines; C575935:CXCL12 protein, rat; D002491:Central Nervous System Agents; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D000080027:Cyclams; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D019332:Endothelin-1; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: Forced limb-use; functional recovery; neurogenesis; stroke; stromal cell-derived factor-1