title: A Clinically Relevant Closed-Head Model of Single and Repeat Concussive Injury in the Adult Rat Using a Controlled Cortical Impact Device.
abstract: Repeat concussions (RC) can result in significant long-term neurological consequences and increased risk for neurodegenerative disease compared with single concussion (SC). Mechanisms underlying this difference are poorly understood and best elucidated using an animal model. To the best of our knowledge, there is no closed-head model in the adult rat using a commercially available device. We developed a novel and clinically relevant closed-head injury (CHI) model of both SC and RC in the adult rat using a controlled cortical impact (CCI) device. Adult rats received either a single or repeat CHI (three injuries, 48 h apart), and acute deficits in sensorimotor and locomotor function (foot fault; open field), memory (novel object), and anxiety (open field; corticosterone [CORT]) were measured. Assessment of cellular pathology was also conducted. Within the first week post-CHI, rats with SC or RC showed similar deficits in motor coordination, decreased locomotion, and higher resting CORT levels. Rats with an SC had memory deficits post-injury day (PID) 3 that recovered to sham levels by PID 7; however, rats with RC continued to show memory deficits. No obvious gross pathology was observed on the cortical surface or in coronal sections. Further examination showed thinning of the cortex and corpus callosum in RC animals compared with shams and increased axonal pathology in the corpus callosum of both SC and RC animals. Our data present a model of CHI that results in clinically relevant markers of concussion and an early differentiation between SC and RC.
authors.affiliation: 1 Department of Biological Sciences, DePaul University , Chicago, Illinois.
authors.forename: Naseem
authors.initials: N
authors.lastname: Jamnia
authors.affiliation: 2 Department of Physiology & Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.
authors.forename: Janice H
authors.initials: JH
authors.lastname: Urban
authors.affiliation: 3 Center for Stem Cell & Regenerative Medicine, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.|4 Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Stutzmann
authors.affiliation: 3 Center for Stem Cell & Regenerative Medicine, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.|4 Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Chiren
authors.affiliation: 3 Center for Stem Cell & Regenerative Medicine, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.|4 Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.
authors.forename: Emily
authors.initials: E
authors.lastname: Reisenbigler
authors.affiliation: 3 Center for Stem Cell & Regenerative Medicine, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.|4 Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.
authors.forename: Robert
authors.initials: R
authors.lastname: Marr
authors.affiliation: 3 Center for Stem Cell & Regenerative Medicine, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.|4 Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science , North Chicago, Illinois.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Peterson
authors.affiliation: 1 Department of Biological Sciences, DePaul University , Chicago, Illinois.
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Kozlowski
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001924:Brain Concussion / Q000150:complications / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology*; D003337:Corpus Callosum / Q000473:pathology*; D004195:Disease Models, Animal; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D009043:Motor Activity / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans
keywords: controlled cortical impact; learning and memory; locomotor function; models of brain injury; rat