title: Histamine promotes locomotion recovery after spinal cord hemisection via inhibiting astrocytic scar formation.
abstract: OBJECTIVE
  This study investigated whether histamine could play a protective role in pathophysiological response of spinal cord injury (SCI) and regulate the glial scar formation.
  
  
  METHODS
  Functional assessment and histological analyses were performed to investigate the effect of histamine after SCI. Histidine decarboxylase knockout (HDC(-/-)) mice were used to confirm the action of histamine. Selective antagonists for H1 and H2 receptors were utilized in vivo and in vitro to verify the functional properties of histamine on astrogliosis.
  
  
  RESULTS
  The local administration of histamine significantly attenuated the tissue damage and glial scar formation after SCI. In particular, the astrogliosis and neurocan expression found around the lesion were significantly suppressed by histamine. Immunofluorescent staining for neurofilament showed that histamine promoted axonal growth across the glial scar. The HDC(-/-) mice, lacking in endogenous histamine, showed lower behavior score, increased lesion size and astrogliosis, as compared with the wild types. The effect of histamine on locomotor recovery and reactive astrogliosis is reversed by H1 receptor antagonist but not H2 receptor antagonist.
  
  
  CONCLUSIONS
  Our results indicate that histamine significantly improved the chronic locomotor recovery via attenuating astrogliosis after SCI by stimulating histamine H1 receptor. This study highlights a therapeutic potential of histamine and its related drugs for SCI.
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Ru-Jia
authors.initials: RJ
authors.lastname: Liao
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Xiang-Nan
authors.initials: XN
authors.lastname: Zhang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D017442:Histamine Agonists; D018696:Neuroprotective Agents; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D006640:Histidine Decarboxylase
keywords: Astrocyte; Histamine; Scar; Spinal cord injury