title: Electromagnetic controlled cortical impact device for precise, graded experimental traumatic brain injury.
abstract: Genetically modified mice represent useful tools for traumatic brain injury (TBI) research and attractive preclinical models for the development of novel therapeutics. Experimental methods that minimize the number of mice needed may increase the pace of discovery. With this in mind, we developed and characterized a prototype electromagnetic (EM) controlled cortical impact device along with refined surgical and behavioral testing techniques. By varying the depth of impact between 1.0 and 3.0 mm, we found that the EM device was capable of producing a broad range of injury severities. Histologically, 2.0-mm impact depth injuries produced by the EM device were similar to 1.0-mm impact depth injuries produced by a commercially available pneumatic device. Behaviorally, 2.0-, 2.5-, and 3.0-mm impacts impaired hidden platform and probe trial water maze performance, whereas 1.5-mm impacts did not. Rotorod and visible platform water maze deficits were also found following 2.5- and 3.0-mm impacts. No impairment of conditioned fear performance was detected. No differences were found between sexes of mice. Inter-operator reliability was very good. Behaviorally, we found that we could statistically distinguish between injury depths differing by 0.5 mm using 12 mice per group and between injury depths differing by 1.0 mm with 7-8 mice per group. Thus, the EM impactor and refined surgical and behavioral testing techniques may offer a reliable and convenient framework for preclinical TBI research involving mice.
authors: Department of Neurology, Hope Center for Neurological Disorders, Washington University, St. Louis, Missouri, USA. brodyd@neuro.wustl.edu
authors: David L
authors: DL
authors: Brody
authors: Christine
authors: C
authors: Mac Donald
authors: Chad C
authors: CC
authors: Kessens
authors: Carla
authors: C
authors: Yuede
authors: Maia
authors: M
authors: Parsadanian
authors: Mike
authors: M
authors: Spinner
authors: Eddie
authors: E
authors: Kim
authors: Katherine E
authors: KE
authors: Schwetye
authors: David M
authors: DM
authors: Holtzman
authors: Philip V
authors: PV
authors: Bayly
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D002138:Calibration; D002540:Cerebral Cortex / Q000473:pathology*; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D055590:Electromagnetic Phenomena; D005239:Fear / Q000502:physiology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009010:Monte Carlo Method; D009462:Neurology / Q000295:instrumentation*; D004856:Postural Balance / Q000502:physiology; D015203:Reproducibility of Results; D013238:Stereotaxic Techniques / Q000295:instrumentation