Citation

Ratliff WA, Qubty D, Delic V, Pick CG, Citron B. J. Neurotrauma 2020; ePub(ePub): ePub.

Affiliation

Rutgers New Jersey Medical School, 12286, Department of Pharmacology, Physiology, & Neuroscience, Newark, New Jersey, United States; bruce.citron@rutgers.edu.

Copyright

(Copyright © 2020, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2020.7005

PMID

32292111

Abstract

The worldwide incidence of traumatic brain injury (TBI) is approximately 0.5% per year and the frequency is significantly higher among military personnel and athletes. Repetitive TBIs are associated with military and athletic activities and typically involve more severe consequences. The majority of TBIs are mild however these still can result in long term cognitive deficits and there is currently no effective treatment. tert-butylhydroquinone (tBHQ) and pioglitazone can activate the Nrf2 and PPAR- transcription factors, respectively, and each has been shown to be neuroprotective in various model systems. We examined behavioral and gene expression changes after repetitive mild TBI followed by simultaneous treatment with both factors. We used a repetitive closed head injury of mice involving five injuries with a one-week interval between each TBI. We found that memory performance was significantly reduced by the injuries, unless the TBIs were followed by the tBHQ and pioglitazone administrations. Certain genes, e.g., growth hormone and osteopontin, were downregulated by the injury and this was reversed by the treatment while other genes, e.g., a tumor necrosis factor receptor, were upregulated by the injury and restored if the post-injury treatment was administered. Analysis of gene expression levels affected by the injury and/or the treatment point to potential mechanisms that could be exploited therapeutically.

Language: en

Keywords

ANIMAL STUDIES; BEHAVIORAL ASSESSMENTS; GENETIC FACTORS; TRAUMATIC BRAIN INJURY