title: Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury.
abstract: Surgically induced brain injury (SBI) results in brain edema and neurological decline. Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases. In this study, we investigated the pretreatment effect of VA in a rat model of SBI. A total of 57 male Sprague-Dawley rats were use in four groups: sham, SBI + vehicle, SBI + low dose (100 mg/kg) VA, and SBI + high dose (300 mg/kg) VA. SBI was induced by partially resecting right frontal lobes. Shams underwent identical surgical procedures without brain resection. VA or vehicle was administered subcutaneously 30 min prior to SBI. At 24 and 72 h post SBI, neurobehavior and brain water content were assessed as well as matrix metalloproteinases (MMPs) activities. There was significantly higher brain water content within the right frontal lobe in SBI rats than in shams. Without neurobehavioral improvements, the low-dose but not high-dose VA significantly reduced brain edema at 24 h post SBI. The protection tends to persist to 72 h post SBI. At 24 h post SBI, low-dose VA did not significantly reduce the elevated MMP-9 activity associated with SBI. In conclusion, VA pretreatment attenuated brain edema at 24 h after SBI but lacked MMP inhibition. The single dose VA was not associated with neurobehavioral benefits.
authors.affiliation: Department of Anesthesiology, Loma Linda University, Room 2532 LLUMC, 11234 Anderson Street, Loma Linda, CA, 92374, USA.|Division of Physiology, Department of Basic Science, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Division of Physiology, Department of Basic Science, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Woo
authors.affiliation: Division of Physiology, Department of Basic Science, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Prativa
authors.initials: P
authors.lastname: Sherchan
authors.affiliation: Department of Anesthesiology, Loma Linda University, Room 2532 LLUMC, 11234 Anderson Street, Loma Linda, CA, 92374, USA.
authors.forename: Nikan H
authors.initials: NH
authors.lastname: Khatibi
authors.affiliation: Division of Physiology, Department of Basic Science, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Krafft
authors.affiliation: Division of Physiology, Department of Basic Science, Loma Linda University, Loma Linda, CA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Rolland
authors.affiliation: Department of Anesthesiology, Loma Linda University, 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 Anesthesiology, Loma Linda University, Room 2532 LLUMC, 11234 Anderson Street, Loma Linda, CA, 92374, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Martin
authors.affiliation: Department of Anesthesiology, Loma Linda University, Room 2532 LLUMC, 11234 Anderson Street, Loma Linda, CA, 92374, USA.|Division of Physiology, Department of Basic Science, Loma Linda University, Loma Linda, CA, USA.|Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005625:Frontal Lobe / Q000601:surgery; D007431:Intraoperative Complications; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D019635:Neurosurgical Procedures; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Matrix metalloproteinases; Neurobehavior; Surgically induced brain injury; Water content