title: Thrombin Preconditioning in Surgical Brain Injury in Rats.
abstract: The surgical brain injury model replicates neurosurgical brain parenchymal damage. Postsurgical brain edema correlates with postoperative neurological dysfunction. Intranasal administration is a proven method of delivering therapies to brain tissue. Thrombin preconditioning decreased brain edema and improved neurological outcomes in models of ischemic brain injury. We hypothesized thrombin preconditioning in surgical brain injury may improve postoperative brain edema and neurological outcomes. Adult male Sprague-Dawley rats (n = 78) weighing 285-355 g were randomly assigned to sham or pre-injury treatment: one-time pretreatment 1 day prior, one-time pretreatment 5 days prior, and daily preconditioning for 5 days prior. Treatment arms were divided into vehicle or thrombin therapies, and subdivided into intranasal (thrombin 5 units/50 μL 0.9 % saline) or intracerebral ventricular (thrombin 0.1 unit/10 μL 0.9 % saline) administration. Blinded observers performed neurological testing 24 h after brain injury followed immediately by measurement of brain water content. There was a significant difference in ipsilateral brain water content and neurological outcomes between all treatment groups and the sham group. However, there was no change in brain water content or neurological outcomes between thrombin- and vehicle-treated animals. Thrombin preconditioning did not significantly improve brain edema or neurological function in surgical brain injury in rats.
authors.affiliation: Department of Anesthesiology, Loma Linda University, School of Medicine, 11234 Anderson Street, Loma Linda, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Benggon
authors.affiliation: Department of Basic Science, Division of Physiology, Loma Linda School of Medicine, Loma Linda, CA, USA.
authors.forename: Hank
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Loma Linda University, School of Medicine, Room 2532 LLUMC, 11234 Anderson Street, Loma Linda, CA, 92374, USA. rapplegate@llu.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Applegate
authors.affiliation: Department of Basic Science, Division of Physiology, Loma Linda School of Medicine, Loma Linda, CA, USA.|Department of Anesthesiology, Loma Linda University, School of Medicine, Room 2532 LLUMC, 11234 Anderson Street, Loma Linda, CA, 92374, USA.
authors.forename: John
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000601:surgery; D006490:Hemostatics / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007431:Intraoperative Complications; D019194:Ischemic Preconditioning; D008297:Male; D019635:Neurosurgical Procedures; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D006490:Hemostatics; D013917:Thrombin
keywords: Brain edema; Neurobehavioral signs and symptoms; Surgical brain injury; Thrombin