Citation

Bugay V, Bozdemir E, Vigil FA, Holstein DM, Chun SH, Elliot W, Sprague C, Cavazos JE, Zamora DO, Rule G, Shapiro MS, Lechleiter JD, Brenner R. J. Neurotrauma 2019; ePub(ePub): ePub.

Affiliation

University of Texas Health San Antonio, Cellular and Integrative Physiology , 8403 Floyd Curl Drive , UT Health Science Center San Antonio , San Antonio, Texas, United States , 78229 ; brennerr@uthscsa.edu.

Copyright

(Copyright © 2019, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2018.6333

PMID

31025597

Abstract

Repetitive blast traumatic brain injury affects numerous soldiers on the battlefield. Mild traumatic brain injury has been shown to have long-lasting effects with repeated injury. Here we have investigated effects on neuronal excitability following repetitive, mild traumatic brain injury 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 3 consecutive days. While a single exposure did not reveal trauma as indicated by the GFAP indicator, 3 repetitive blasts did show significant increases. As well, mice had increased indicator of inflammation (Iba-1), and increased tau, tau phosphorylation, and altered cytokine levels in spleen. Video-EEG monitoring 48 hours 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 at least 46% (6/13) of the mice developed spontaneous seizures. Patch clamp recording of dentate gyrus hippocampus neurons 48 hours post-blast TBI demonstrated a shortened latency to the first spike, and hyperpolarization of action potential threshold. We also found that EPSC 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.

Language: en

Keywords

ANIMAL STUDIES; EPILEPSY; TRAUMATIC BRAIN INJURY