Center for Injury Research and Prevention

Concussion Induces Hippocampal Circuitry Disruption in Swine.

TitleConcussion Induces Hippocampal Circuitry Disruption in Swine.
Publication TypeJournal Article
Year of Publication2017
AuthorsWolf JA, Johnson BN, Johnson VE, Putt ME, Browne KD, Mietus CJ, Brown DP, Wofford KL, Smith DH, M Grady S, Cohen AS, D Cullen K
JournalJ Neurotrauma
Volume34
Issue14
Pagination2303-2314
Date Published07/2017
Type of Articlejournal
ISSN1557-9042
KeywordsAnimals, Brain Concussion, Disease Models, Animal, Female, Hippocampus, 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.

DOI10.1089/neu.2016.4848
Alternate JournalJ. Neurotrauma
PubMed ID28298170
PubMed Central IDPMC5510797
Grant ListR01 NS101108 / NS / NINDS NIH HHS / United States
IK2 RX001479 / RX / RRD VA / United States
T32 NS043126 / NS / NINDS NIH HHS / United States
U54 HD086984 / HD / NICHD NIH HHS / United States
R01 NS069629 / NS / NINDS NIH HHS / United States
I01 RX001097 / RX / RRD VA / United States
R01 NS050598 / NS / NINDS NIH HHS / United States
R37 HD059288 / HD / NICHD NIH HHS / United States