title: Combination of cyclosporine and erythropoietin improves brain infarct size and neurological function in rats after ischemic stroke.
abstract: BACKGROUND
  This study tested the superiority of combined cyclosporine A (CsA)-erythropoietin (EPO) therapy compared with either one in limiting brain infarction area (BIA) and preserving neurological function in rat after ischemic stroke (IS).
  
  
  METHODS
  Fifty adult-male SD rats were equally divided into sham control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48 h after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group 3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA and EPO (same route and dosage as groups 3 and 4) treatment (group 5) after occlusion of distal left internal carotid artery.
  
  
  RESULTS
  BIA on day 21 after acute IS was higher in group 2 than in other groups and lowest in group 5 (all p < 0.01). The sensorimotor functional test showed higher frequency of left turning in group 2 than in other groups and lowest in group 5 (all p < 0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were higher in group 2 than in other groups and lowest in group 1 and 5, whereas the anti-apoptotic markers exhibited an opposite trend (all p < 0.05). The expressions of inflammatory and oxidized protein were higher in group 2 than in other groups and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and other groups (all p < 0.05). The number of aquaporin-4+ and glial fibrillary acid protein+ stained cells were higher in group 2 as compared to other groups and lowest in groups 1 and 5 (all p < 0.01).
  
  
  CONCLUSIONS
  combined treatment with CsA and EPO was superior to either one alone in protecting rat brain from ischemic damage after IS.
authors.affiliation: Division of Trauma, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chun-Man
authors.initials: CM
authors.lastname: Yuen
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Shao
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051401:Aquaporin 4 / Q000378:metabolism; D020520:Brain Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D045304:Cytochromes c / Q000378:metabolism; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D004921:Erythropoietin; D016572:Cyclosporine; D045304:Cytochromes c