A Mouse Model of Repetitive Blast Traumatic Brain Injury Reveals Post-Trauma Seizures and Increased Neuronal Excitability

Vladislav Bugay, Eda Bozdemir, Fabio A. Vigil, Sang H. Chun, Deborah M. Holstein, William R. Elliott, Cassie J. Sprague, Jose E. Cavazos, David O. Zamora, Gregory Rule, Mark S. Shapiro, James D. Lechleiter, Robert Brenner

Research output: Contribution to journalArticle

Abstract

Repetitive blast traumatic brain injury (TBI) affects numerous soldiers on the battlefield. Mild TBI has been shown to have long-lasting effects with repeated injury. We have investigated effects on neuronal excitability after repetitive, mild TBI in a mouse model of blast-induced brain injury. We exposed mice to mild blast trauma of an average peak overpressure of 14.6 psi, repeated across three consecutive days. While a single exposure did not reveal trauma as indicated by the glial fibrillary acidic protein indicator, three repetitive blasts did show significant increases. As well, mice had an increased indicator of inflammation (Iba-1) and increased tau, tau phosphorylation, and altered cytokine levels in the spleen. Video-electroencephalographic monitoring 48 h after the final blast exposure demonstrated seizures in 50% (12/24) of the mice, most of which were non-convulsive seizures. Long-term monitoring revealed that spontaneous seizures developed in at least 46% (6/13) of the mice. Patch clamp recording of dentate gyrus hippocampus neurons 48 h post-blast TBI demonstrated a shortened latency to the first spike and hyperpolarization of action potential threshold. We also found that evoked excitatory postsynaptic current amplitudes were significantly increased. These findings indicate that mild, repetitive blast exposures cause increases in neuronal excitability and seizures and eventual epilepsy development in some animals. The non-convulsive nature of the seizures suggests that subclinical seizures may occur in individuals experiencing even mild blast events, if repeated.

Original languageEnglish (US)
Pages (from-to)248-261
Number of pages14
JournalJournal of Neurotrauma
Volume37
Issue number2
DOIs
StatePublished - Jan 15 2020

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Seizures
Brain Concussion
Wounds and Injuries
Parahippocampal Gyrus
Partial Epilepsy
Excitatory Postsynaptic Potentials
Glial Fibrillary Acidic Protein
Dentate Gyrus
Military Personnel
Brain Injuries
Action Potentials
Epilepsy
Spleen
Phosphorylation
Traumatic Brain Injury
Cytokines
Inflammation
Neurons

Keywords

  • blast
  • epilepsy
  • mild traumatic brain injury
  • repetitive mTBI
  • seizure
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

A Mouse Model of Repetitive Blast Traumatic Brain Injury Reveals Post-Trauma Seizures and Increased Neuronal Excitability. / Bugay, Vladislav; Bozdemir, Eda; Vigil, Fabio A.; Chun, Sang H.; Holstein, Deborah M.; Elliott, William R.; Sprague, Cassie J.; Cavazos, Jose E.; Zamora, David O.; Rule, Gregory; Shapiro, Mark S.; Lechleiter, James D.; Brenner, Robert.

In: Journal of Neurotrauma, Vol. 37, No. 2, 15.01.2020, p. 248-261.

Research output: Contribution to journalArticle

Bugay, V, Bozdemir, E, Vigil, FA, Chun, SH, Holstein, DM, Elliott, WR, Sprague, CJ, Cavazos, JE, Zamora, DO, Rule, G, Shapiro, MS, Lechleiter, JD & Brenner, R 2020, 'A Mouse Model of Repetitive Blast Traumatic Brain Injury Reveals Post-Trauma Seizures and Increased Neuronal Excitability', Journal of Neurotrauma, vol. 37, no. 2, pp. 248-261. https://doi.org/10.1089/neu.2018.6333
Bugay, Vladislav ; Bozdemir, Eda ; Vigil, Fabio A. ; Chun, Sang H. ; Holstein, Deborah M. ; Elliott, William R. ; Sprague, Cassie J. ; Cavazos, Jose E. ; Zamora, David O. ; Rule, Gregory ; Shapiro, Mark S. ; Lechleiter, James D. ; Brenner, Robert. / A Mouse Model of Repetitive Blast Traumatic Brain Injury Reveals Post-Trauma Seizures and Increased Neuronal Excitability. In: Journal of Neurotrauma. 2020 ; Vol. 37, No. 2. pp. 248-261.
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