Blast Traumatic Brain Injury Induces Long-Term Alterations in Inflammatory Gene Expression in Chinchilla Brains

Abstract

Blast traumatic brain injury (bTBI) due to high-intensity impulsive noise exposure from explosions and munitions exposure is highly prevalent among military personnel, which leads to diffuse brain injury resulting in a spectrum of brain dysfunction and cognitive deficits. The resultant prolonged neuroinflammation and consequent failure of inflammation resolution is a key contributor to long-term complications, including post-traumatic stress disorder and early-onset of neurodegenerative disease; however, there is little evidence for the duration and extent of long term neuroinflammation in distinct brain regions. To investigate this, due to human-like audiogram, we use chinchillas as an in-vivo bTBI model to analyze the relative gene expression of inflammatory markers (TNF, TGF{beta}2, Gal1, HSP90, S100B, NRGN, MAPK14, IL8, NFL, and BDNF) in the hippocampus, striatum, and higher centers of the auditory pathway 90 days following varying intensities of blast exposures (144 dB, 155 dB, and 172 dB sound pressure level). Our study revealed aberrant gene expression across all analyzed brain regions and all injury conditions; however, no specific pattern emerged. Many of the inflammatory markers were downregulated, suggesting a possible attempt by the brain to overcome prior inflammation. Conversely, the hippocampus, striatum, inferior colliculus, and medial geniculate body all exhibited upregulation of inflammatory markers, including the TBI prognostic marker, S100B. Thus, chinchilla brains exhibit evidence of prolonged neuroinflammation 90 days following injury, even during mild blast exposure. Ultimately, the observed alterations in the gene expression of inflammatory markers may contribute to the long-term neurological dysfunction and neurodegenerative disease experienced by veterans and other bTBI patients.