title: Concussion Induces Hippocampal Circuitry Disruption in Swine.
abstract: Hippocampal-dependent deficits in learning and memory formation are a prominent feature of traumatic brain injury (TBI); however, the role of the hippocampus in cognitive dysfunction after concussion (mild TBI) is unknown. We therefore investigated functional and structural changes in the swine hippocampus following TBI using a model of head rotational acceleration that closely replicates the biomechanics and neuropathology of closed-head TBI in humans. We examined neurophysiological changes using a novel ex vivo hippocampal slice paradigm with extracellular stimulation and recording in the dentate gyrus and CA1 occurring at 7 days following non-impact inertial TBI in swine. Hippocampal neurophysiology post-injury revealed reduced axonal function, synaptic dysfunction, and regional hyperexcitability at one week following even "mild" injury levels. Moreover, these neurophysiological changes occurred in the apparent absence of intra-hippocampal neuronal or axonal degeneration. Input-output curves demonstrated an elevated excitatory post-synaptic potential (EPSP) output for a given fiber volley input in injured versus sham animals, suggesting a form of homeostatic plasticity that manifested as a compensatory response to decreased axonal function in post-synaptic regions. These data indicate that closed-head rotational acceleration-induced TBI, the common cause of concussion in humans, may induce significant alterations in hippocampal circuitry function that have not resolved at 7 days post-injury. This circuitry dysfunction may underlie some of the post-concussion symptomatology associated with the hippocampus, such as post-traumatic amnesia and ongoing cognitive deficits.
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|2 Center for Neurotrauma, Neurodegeneration, and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center , Philadelphia, Pennsylvania.
authors.forename: John A
authors.initials: JA
authors.lastname: Wolf
authors.affiliation: 3 Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania.
authors.forename: Brian N
authors.initials: BN
authors.lastname: Johnson
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Johnson
authors.affiliation: 4 Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Putt
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|2 Center for Neurotrauma, Neurodegeneration, and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center , Philadelphia, Pennsylvania.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Browne
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Constance J
authors.initials: CJ
authors.lastname: Mietus
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|2 Center for Neurotrauma, Neurodegeneration, and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center , Philadelphia, Pennsylvania.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Brown
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|2 Center for Neurotrauma, Neurodegeneration, and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center , Philadelphia, Pennsylvania.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Wofford
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: M Sean
authors.initials: MS
authors.lastname: Grady
authors.affiliation: 3 Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania.
authors.forename: Akiva S
authors.initials: AS
authors.lastname: Cohen
authors.affiliation: 1 Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.|2 Center for Neurotrauma, Neurodegeneration, and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center , Philadelphia, Pennsylvania.
authors.forename: D Kacy
authors.initials: DK
authors.lastname: Cullen
mesh_terms: D000818:Animals; D001924:Brain Concussion / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D013552:Swine
keywords: axonal pathology; concussion; epileptogenesis; hippocampus; mild TBI; traumatic brain injury