title: Effect of dexmedetomidine on brain edema and neurological outcomes in surgical brain injury in rats.
abstract: BACKGROUND
  Surgical brain injury (SBI) is damage to functional brain tissue resulting from neurosurgical manipulations such as sharp dissection, electrocautery, retraction, and direct applied pressure. Brain edema is the major contributor to morbidity with inflammation, necrosis, oxidative stress, and apoptosis likely playing smaller roles. Effective therapies for SBI may improve neurological outcomes and postoperative morbidities associated with brain surgery. Previous studies show an adrenergic correlation to blood-brain barrier control. The α-2 receptor agonist dexmedetomidine (DEX) has been shown to improve neurological outcomes in stroke models. We hypothesized that DEX may reduce brain edema and improve neurological outcomes in a rat model of SBI.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 63) weighing 280 to 350 g were randomly assigned to 1 of 4 IP treatment groups: sham IP, vehicle IP, DEX 10 mg/kg, and DEX 30 mg/kg. Treatments were given 30 min before SBI. These treatment groups were repeated to observe the physiologic impact of DEX on mean arterial blood pressure (MAP), heart rate (HR), and blood glucose on SBI naïve animals. Rats were also assigned to 4 postinjury IV treatment groups: sham IV, vehicle IV, DEX 10/5, and DEX 30/15 (DEX group doses were 10 and 30 mg/kg/hr, with 5 and 15 mg/kg initial loading doses, respectively). Initial loading doses began 20 min after SBI, followed by 2 h of infusion. SBI animals were subjected to neurological testing 24 h after brain injury by a blinded observer, promptly killed, and brain water content measured via the dry/wet weight method.
  
  
  RESULTS
  All treatment groups showed a significant difference in ipsilateral frontal brain water content and neurological scores when compared with sham animals. However, there was no difference between DEX-treated and vehicle animals. Physiologic monitoring showed treatment with low or high doses of DEX significantly decreased MAP and HR, and briefly increased blood glucose compared with naïve or vehicle-treated animals.
  
  
  CONCLUSIONS
  DEX administration did not reduce brain edema or improve neurological function after SBI in this study. The statistical difference in brain water content and neurological scores when comparing sham treatment to vehicle and DEX treatments shows consistent reproduction of this model. Significant changes in MAP, HR, and blood glucose after DEX as compared to vehicle and sham treatments suggest appropriate delivery of drug.
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, 11234 Anderson St, Room 2562B, Loma Linda, CA 92354, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Benggon
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Richard
authors.initials: R
authors.lastname: Applegate
authors.forename: Robert
authors.initials: R
authors.lastname: Martin
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D001786:Blood Glucose; D020927:Dexmedetomidine