title: Pre- and post-treatment with cyclosporine A in a rat model of transient focal cerebral ischaemia with multimodal MRI screening.
abstract: BACKGROUND
  Irreversible damage may occur at reperfusion after sustained cerebral ischaemia.
  
  
  OBJECTIVE
  We investigated the value of cyclosporine A for reducing the infarct size in a model of transient middle cerebral artery occlusion.
  
  
  METHODS
  Twenty-seven Sprague-Dawley rats sustained a middle cerebral artery occlusion of one-hour. Acute multimodal Magnetic Resonance Imaging (MRI) was used during occlusion to confirm the success of surgery and measure baseline lesion size. Animals were randomly treated by: (i) intracarotid cyclosporine A (10 mg/kg) 20 mins before middle cerebral artery occlusion (pretreatment group); (ii) intracarotid cyclosporine A (10 mg/kg) immediately after reperfusion (post-treatment group); and (iii) intracarotid saline immediately after reperfusion.
  
  
  RESULTS
  Histopathological measurements on day 1 showed a significant reduction of infarct size in the pretreatment group compared to the post-treatment (percentage values of ipsilateral hemispheres: 16 ± 5% vs. 29 ± 11%, P = 0·004) and saline groups (16 ± 5% vs. 42 ± 12%, P = 0·015). No significant difference was observed between the post-treatment and saline groups (P = 0·065). Behavioural examinations on day 1 showed no significant difference between groups. Immunohistochemistry showed a statistically significant reduction of microglial cell count in the pretreatment group compared to either saline or cyclosporine A post-treatment groups.
  
  
  CONCLUSIONS
  We conclude that intracarotid cyclosporine A is effective in reducing infarct size when given prior to ischaemia, but not when administered at reperfusion.
authors.affiliation: Université de Lyon, CREATIS; CNRS UMR5220, INSERM U1044, INSA-Lyon; Université Lyon 1, Hospices Civils de Lyon, France.
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Cho
authors.forename: Pierre
authors.initials: P
authors.lastname: Aguettaz
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.forename: Christiane
authors.initials: C
authors.lastname: Charriaut-Marlangue
authors.forename: Adrien
authors.initials: A
authors.lastname: Riou
authors.forename: Yves
authors.initials: Y
authors.lastname: Berthezène
authors.forename: Norbert
authors.initials: N
authors.lastname: Nighoghossian
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
authors.forename: Marlène
authors.initials: M
authors.lastname: Wiart
authors.forename: Fabien
authors.initials: F
authors.lastname: Chauveau
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D016572:Cyclosporine