title: Cyclophilin A/Cluster of Differentiation 147 Interactions Participate in Early Brain Injury After Subarachnoid Hemorrhage in Rats.
abstract: OBJECTIVE
  Cyclophilin A has been found to be involved in many inflammatory diseases via its receptor, cluster of differentiation 147 (CD147). This study was designed to estimate the potential role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury.
  
  
  METHODS
  Controlled in vivo laboratory study.
  
  
  METHODS
  Animal research laboratory.
  
  
  METHODS
  Two hundred ninety adult male Sprague-Dawley rats weighing 300-350 g.
  
  
  METHODS
  A prechiasmatic cistern single-injection model was used to produce experimental subarachnoid hemorrhage in Sprague-Dawley rats. The expressions of cyclophilin A and CD147, the interaction between cyclophilin A and CD147, and the secretion of cyclophilin A were assessed using immunofluorescence staining, Western blot analysis, and coimmunoprecipitation analysis. Down-regulation of cyclophilin A expression by small interfering RNA was performed, and recombinant human cyclophilin A and monoclonal antibody of CD147 were exploited to study the role of cyclophilin A/CD147 in subarachnoid hemorrhage-induced early brain injury.
  
  
  RESULTS
  The expressions of cyclophilin A and CD147 in neurons were higher than that of the sham group and peaked at 24 hours after subarachnoid hemorrhage. Compared with sham group, subarachnoid hemorrhage was found to increase the secretion of cyclophilin A and the interaction between cyclophilin A and CD147. Cyclophilin A small interfering RNA and anti-CD147 treatments were found to ameliorate subarachnoid hemorrhage-induced early brain injury, including cortical apoptosis and necrosis, brain edema, blood-brain barrier damage, and neurobehavioral deficits. Cyclophilin A small interfering RNA and anti-CD147 treatments also decreased the phosphorylation of extracellular signal-regulated protein kinase 1/2, the protein levels of p53 and caspase-3, and the level of active nuclear factor-κB. Finally, recombinant human cyclophilin A treatment resulted in an opposite effect, which was inhibited by anti-CD147 treatment.
  
  
  CONCLUSIONS
  Cyclophilin A/CD147 interactions may participate in subarachnoid hemorrhage-induced early brain injury via increasing neuronal apoptosis pathway, at least partly through the ERK1/2-nuclear factor-κB pathway. Cyclophilin A/CD147 may be a suitable therapeutic target for subarachnoid hemorrhage.
authors.affiliation: 1Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. 2Department of Rehabilitation Medicine, Zhangjiagang Hospital of Traditional Chinese Medicine, Soochow University, Suzhou, Jiangsu Province, China. 3Department of Neurosurgery, Zhangjiagang Hospital of Traditional Chinese Medicine, Soochow University, Suzhou, Jiangsu Province, China.
authors.forename: Baoqi
authors.initials: B
authors.lastname: Dang
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Anju
authors.initials: A
authors.lastname: Gao
authors.forename: Weichun
authors.initials: W
authors.lastname: He
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051926:Basigin / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000378:metabolism; D015153:Blotting, Western; D001929:Brain Edema / Q000503:physiopathology; D001930:Brain Injuries / Q000503:physiopathology*; D021984:Cyclophilin A / Q000502:physiology*; D004195:Disease Models, Animal; D008297:Male; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*
chemical_list: D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D051926:Basigin; D021984:Cyclophilin A