title: Granulocyte colony-stimulating factor protects the brain against experimental stroke via inhibition of apoptosis and inflammation.
abstract: OBJECTIVE
  The molecular mechanisms of the anti-apoptotic and anti-inflammatory properties of granulocyte-colony stimulating factor (G-CSF) following focal cerebral ischemia in rats were examined in this study.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into three groups: sham, middle cerebral artery occlusion (MCAO) non-treatment and MCAO with G-CSF treatment. Focal ischemia was induced with the suture occlusion method for 90 minutes, and treatment was given at the onset of reperfusion. All animals were killed 24 hours after reperfusion. Assessment included neurological scores, infarction volumes, histology, immunofluorescent staining and Western blotting.
  
  
  RESULTS
  G-CSF significantly reduced the infarct volume and ameliorated the early neurological outcome scores. Western blot analysis showed that G-CSF treatment significantly elevated the cIAP2 levels and decreased the activation of caspase 3 in the ischemic cortex compared with the non-treated rats. Immunofluorescent works also showed that G-CSF treatment inhibited both neuronal and glial tumor necrosis factor alpha and interleukin 1beta expressions.
  
  
  CONCLUSIONS
  The neuronal anti-apoptotic action of G-CSF may be mediated in part by the anti-apoptotic protein cIAP2. G-CSF also exerts anti-inflammatory actions after focal cerebral ischemia by preventing both neuronal and glial pro-inflammatory cytokine expressions.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Solaroglu
authors.forename: Julian
authors.initials: J
authors.lastname: Cahill
authors.forename: Tamiji
authors.initials: T
authors.lastname: Tsubokawa
authors.forename: Ethem
authors.initials: E
authors.lastname: Beskonakli
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000517:prevention & control; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009460:Neurologic Examination; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051034:Inhibitor of Apoptosis Proteins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase