title: The protective effect of SCR(15-18) on cerebral ischemia-reperfusion injury.
abstract: OBJECTIVE
  Soluble complement receptor type 1 (sCR1), a potent inhibitor of complement activation, has been shown to protect brain cells against cerebral ischemic/reperfusion (CI/R) injury due to its decay-accelerating activity for C3/C5 convertase and co-factor  activity for C3b/C4b degradation. However, the effect of short consensus repeats (SCRs) 15-18, one of active domains of sCR1 with high C3b/C4b degradability, has not been demonstrated. Here, we investigated the protective effect of recombinant SCR(15-18) protein in middle  cerebral artery occlusion (MCAO)-induced focal CI/R injury.
  
  
  METHODS
  Recombinant SCR(15-18) protein was successfully expressed in Escherichia coli and refolded to its optimal bioactivity. Seventy-five Sprague-Dawley rats were randomly assigned into three  groups: sham-operated group, CI/R group, and SCR(15-18)+CI/R group pretreated with 20 mg/kg SCR(15-18) protein. After 2 hours of MCAO and subsequent 24 hours of reperfusion, rats were evaluated for neurological deficits and cerebral infarction. Polymorphonuclear  leukocyte accumulation, C3b deposition, and morphological changes in cerebral tissue were also estimated.
  
  
  RESULTS
  SCR(15-18) pretreatment induced a 20% reduction of infarct size and an improvement of neurological function with 22·2% decrease of neurological  deficit scores. Inhibition of cerebral neutrophils infiltration by SCR(15-18) was indicated from the reduction of myeloperoxidase activity in SCR(15-18)+CI/R rats. Decreased C3b deposition and improved morphological changes were also found in cerebral tissue  of SCR(15-18)-treated rats.
  
  
  CONCLUSIONS
  Our studies suggest a definitive moderately protective effect of SCR(15-18) against CI/R damage and provide preclinical experimental evidence supporting the possibility of using it as a small anti-complement  therapeutic agent for CI/R injury therapy.
authors: Department of Microbiology, Third Military Medical University, Chongqing, China.
authors: Shu
authors: S
authors: Li
authors: Jinhong
authors: J
authors: Xian
authors: Li
authors: L
authors: He
authors: Xue
authors: X
authors: Luo
authors: Bing
authors: B
authors: Tan
authors: Yongtao
authors: Y
authors: Yang
authors: Gaoke
authors: G
authors: Liu
authors: Zhengqing
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D003167:Complement Activation / Q000187:drug effects*; D003179:Complement C3b / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009504:Neutrophils; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011951:Receptors, Complement / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011951:Receptors, Complement; D011994:Recombinant Proteins; D003179:Complement C3b; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase