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Journal article
Concussion Induces Hippocampal Circuitry Disruption in Swine
Journal of neurotrauma, v 34(14), pp 2303-2314
15 Jul 2017
PMID: 28298170
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Concussion Induces Hippocampal Circuitry Disruption in Swine
- Creators
- John A. Wolf - University of PennsylvaniaBrian N. Johnson - Children's Hospital of PhiladelphiaVictoria E. Johnson - University of PennsylvaniaMary E. Putt - University of PennsylvaniaKevin D. Browne - University of PennsylvaniaConstance J. Mietus - University of PennsylvaniaDaniel P. Brown - University of PennsylvaniaKathryn L. Wofford - University of PennsylvaniaDouglas H. Smith - University of PennsylvaniaM. Sean Grady - University of PennsylvaniaAkiva S. Cohen - Children's Hospital of PhiladelphiaD. Kacy Cullen - University of Pennsylvania
- Publication Details
- Journal of neurotrauma, v 34(14), pp 2303-2314
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 12
- Grant note
- B1097-I / Department of Veterans Affairs [Rehabilitation Research & Development (Merit Review Award) CURE Taking Flight Award R01NS101108 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R37-HD-059288 / National Institutes of Health [NICHD]; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) I01RX001097 / Veterans Affairs; US Department of Veterans Affairs R01-NS-050598; R01-NS-069629; T32-NS043126 / National Institutes of Health [NINDS]; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) U54 HD086984 / National Institutes of Health [NICH] IK2-RX001479 / Department of Veterans Affairs [Rehabilitation Research & Development (Career Development Award) U54HD086984 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000404995000013
- Scopus ID
- 2-s2.0-85021756179
- Other Identifier
- 991019176801404721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences