title: Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model.
abstract: OBJECTIVE
  In patients who have sustained a traumatic brain injury (TBI), hypothermia therapy has not shown efficacy in multicenter clinical trials. Armed with the post hoc data from the latest clinical trial (National Acute Brain Injury Study: Hypothermia II), the authors hypothesized that hypothermia may be beneficial in an acute subdural hematoma (SDH) rat model by blunting the effects of ischemia/reperfusion injury. The major aim of this study was to test the efficacy of temperature management in reducing brain damage after acute SDH.
  
  
  METHODS
  The rats were induced with acute SDH and placed into 1 of 4 groups: 1) normothermia group (37°C); 2) early hypothermia group, head and body temperature reduced to 33°C 30 minutes prior to craniotomy; 3) late hypothermia group, temperature lowered to 33°C 30 minutes after decompression; and 4) sham group, no acute SDH (only craniotomy with normothermia). To assess for neuronal and glial cell damage, the authors analyzed microdialysate concentrations of GFAP and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) by using a 100-kD probe. Fluoro-Jade B-positive neurons and injury volume with 2,3,5-triphenyltetrazolium chloride staining were also measured.
  
  
  RESULTS
  In the early phase of reperfusion (30 minutes, 2.5 hours after decompression), extracellular UCH-L1 in the early hypothermia group was significantly lower than in the normothermia group (early, 4.9 ± 1.0 ng/dl; late, 35.2 ± 12.1 ng/dl; normothermia, 50.20 ± 28.3 ng/dl; sham, 3.1 ± 1.3 ng/dl; early vs normothermia, p < 0.01; sham vs normothermia, p < 0.01, analyzed using ANOVA followed by a post hoc Bonferroni test). In the late phase of reperfusion (> 2.5 hours after decompression), extracellular GFAP in the early hypothermia group was also lower than in the normothermia and late hypothermia groups (early, 5.5 ± 2.9 ng/dl; late, 7.4 ± 3.4 ng/dl; normothermia, 15.3 ± 8.4 ng/dl; sham, 3.3 ± 1.0 ng/dl; normothermia vs sham; p < 0.01). The number of Fluoro-Jade B-positive cells in the early hypothermia group was significantly smaller than that in the normothermia group (normothermia vs early: 774,588 ± 162,173 vs 180,903 ± 42,212, p < 0.05). Also, the injury area and volume were smaller in the early hypothermia group in which hypothermia was induced before craniotomy and cerebral reperfusion (early, 115.2 ± 15.4 mm(3); late, 344.7 ± 29.1 mm(3); normothermia, 311.2 ± 79.2 mm(3); p < 0.05).
  
  
  CONCLUSIONS
  The data suggest that early, preoperatively induced hypothermia could mediate the reduction of neuronal and glial damage in the reperfusion phase of ischemia/reperfusion brain injury.
authors.affiliation: Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. SYokobori@med.miami.edu
authors.forename: Shoji
authors.initials: S
authors.lastname: Yokobori
authors.forename: Shyam
authors.initials: S
authors.lastname: Gajavelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.forename: Jixiang
authors.initials: J
authors.lastname: Mo-Seaney
authors.forename: Helen M
authors.initials: HM
authors.lastname: Bramlett
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
authors.forename: M Ross
authors.initials: MR
authors.lastname: Bullock
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D019299:Decompression, Surgical; D004195:Disease Models, Animal; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020199:Hematoma, Subdural, Acute / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D017551:Microdialysis; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009930:Organic Chemicals; D011300:Preoperative Care / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D009930:Organic Chemicals; C435731:fluoro jade; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase