title: Cystamine improves functional recovery via axon remodeling and neuroprotection after stroke in mice.
abstract: OBJECTIVE
  Stroke is a leading cause of disability. However, there is no pharmacological therapy available for promoting recovery. Although treatment of stroke with cystamine has gained increasing interest, the detailed mechanisms underlying this process remain elusive. Thus, our aim is to examine the effect of cystamine on the function recovery after stroke and investigate further cystamine mechanisms.
  
  
  METHODS
  Adult male C57BL/6J mice were subjected to photothrombotic model of focal stroke or sham operation. Cystamine or saline was administered intraperitoneally at 24 h after stroke. Functional recovery was analyzed using behavioral tests; axon remodeling was analyzed using magnetic resonance diffusion tensor imaging (DTI) and histological assessment. ANA-12, an antagonist of tropomyosin-related kinase B (TrkB), was administrated to examine the mechanisms underlying the neuroprotection mediated by cystamine.
  
  
  RESULTS
  Treatment with cystamine resulted in amelioration of impaired function with concomitant enhancement of axonal remodeling. Cystamine treatment significantly increased brain-derived neurotrophic factor (BDNF) levels and phosphorylation of TrkB in brain after stroke. Cystamine significantly enhanced neuronal progenitor cell proliferation, neuronal survival, and plasticity through BDNF/TrkB pathway.
  
  
  CONCLUSIONS
  These data provide evidence to investigate the promising utility of cystamine for therapy of stroke in a variety of ways, acting principally through BDNF/TrkB pathway.
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.
authors.forename: Pei-Cheng
authors.initials: PC
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiao
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Yang
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Ju
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yao
authors.forename: Gao-Jun
authors.initials: GJ
authors.lastname: Teng
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D001381:Azepines / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002491:Central Nervous System Agents / Q000494:pharmacology; D003538:Cystamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D011897:Random Allocation; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: C559317:ANA 12 compound; D001381:Azepines; D001549:Benzamides; D002491:Central Nervous System Agents; D018696:Neuroprotective Agents; D020813:Receptor, trkB; D003538:Cystamine
keywords: Axonal remodeling; Cystamine; Neuroprotection; Rehabilitation; Stroke