Abstract
Blast-related mild traumatic brain injury induces significant long-term health issues, yet treatment procedures remain underdeveloped. Therapeutic hypothermia has been postulated as a potentially effective therapy. In a Caenorhabditis elegans model, we demonstrate a dose-dependent reduction in lifespan following exposure to blast-like shock waves. Using polyvinyl alcohol, we show that cavitation is a key injurious factor in the damaging shock wave component. Short and long lifespan C. elegans mutants demonstrated the interaction of genetic and environmental longevity-determining factors. Hypothermia reduced the long term effect of shock wave exposure. Thus, we present an effective C. elegans model of long term effects of blast-related mild traumatic brain injury, as well as evidence of the merit of therapeutic hypothermia as a therapy option following blast exposure.
Highlights
Blast-related mild traumatic brain injury has been shown to induce long-term effects including, but not limited to, post-traumatic stress disorder and depression[1], and reduced life expectancy[2]
Worms exposed to 500 shock waves exhibited significantly shorter lifespans compared to those exposed to 100 shock waves, in worms raised on NGM-agar plates, indicating a dose-dependent long term effect of shock wave exposure
We previously showed that using polyvinyl alcohol (PVA), a medium with low cavitation activity, as a medium for exposing
Summary
Blast-related mild traumatic brain injury (br-mTBI) has been shown to induce long-term effects including, but not limited to, post-traumatic stress disorder and depression[1], and reduced life expectancy[2]. While mammalian models are an effective and commonly used tool to investigate br-mTBI, limitations such as low sample size, length of life, and complexity highlight the need for other effective models of br-mTBI3. Despite such shortcomings, progress has still been made in the investigation of potentially effective therapies following traumatic brain injury. We have previously shown that C. elegans offer a viable alternative to mammalian models, as exposure to shock waves results in behavioral changes that share key features with br-mTBI in humans: initial loss of consciousness followed by recovery[9]. We hypothesized that (i) exposure to shock waves reduces C. elegans lifespan in the long term, (ii) this effect is partially dependent on the presence of cavitation, and (iii) therapeutic hypothermia improves the long term outlook of C. elegans survival
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