title: Isoflurane reduces the ischemia reperfusion injury surge: a longitudinal study with MRI.
abstract: BACKGROUND
  Recent studies show neuroprotective benefits of isoflurane (ISO) administered during cerebral ischemia. However, the available studies evaluated cerebral injury only at a single time point following the intervention and thus the longitudinal effect of ISO on ischemic tissues remains to be investigated.
  
  
  OBJECTIVE
  The objective of the present study was to investigate the longitudinal effect of ISO treatment in counteracting the deleterious effect of ischemia by evoking the transcription factor, hypoxia inducible factor-1 (HIF-1), and vascular endothelial growth factor (VEGF).
  
  
  METHODS
  Focal cerebral ischemia was induced in 70 rats by filament medial cerebral artery occlusion (MCAo) method. MCAo rats were randomly assigned to control (90 min ischemia) and MCAo+ISO (90 min ischemia+2% ISO) groups. Infarct volume, edema, intracerebral hemorrhage (ICH), and regional cerebral blood flow (rCBF) were measured in eight in vivo sequential MR imaging sessions for 3 weeks. Western blot analysis and immunofluorescence were used to determine the expression level of HIF-1α (the regulatable subunit of HIF-1) and VEGF proteins.
  
  
  RESULTS
  ISO inhalation during ischemia significantly decreased the surge of infarct volume, edema, ICH, and reduced the mortality rate (p<0.01). ISO transiently altered the rCBF, significantly enhanced the expression of HIF-1α and VEGF, and decreased the immune cell infiltration. Locomotor dysfunction was ameliorated at a significantly faster pace, and the benefit was seen to persist up to three weeks.
  
  
  CONCLUSIONS
  Treatment with ISO during ischemia limits the deadly surge in the dynamics of ischemia reperfusion injury with no observed long-term inverse effect.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, 29425. Electronic address: taheri@musc.edu.
authors.forename: Saeid
authors.initials: S
authors.lastname: Taheri
authors.affiliation: Department of Pediatrics,Medical University of South Carolina, Charleston, SC, 29425.
authors.forename: Anandakumar
authors.initials: A
authors.lastname: Shunmugavel
authors.affiliation: Department of Pediatrics,Medical University of South Carolina, Charleston, SC, 29425.
authors.forename: Danielle
authors.initials: D
authors.lastname: Clark
authors.affiliation: Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, 66045.
authors.forename: Honglian
authors.initials: H
authors.lastname: Shi
mesh_terms: D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D017352:Echo-Planar Imaging; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D007530:Isoflurane / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane
keywords: Intracerebral hemorrhage; Ischemia; Isoflurane; Longitudinal analysis; MRI; Regional cerebral blood flow; Stroke