Abstract

In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short- and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI.

Highlights

  • The increasing prevalence of blast-related mild traumatic brain injury has become a considerable health and economic issue (Hoge et al, 2008)

  • High interindividual variability within shock wave exposure groups was observed in C. elegans even though the subjects were genetically identical and exposed to shock waves under consistent, controlled conditions

  • Using the behavioral endpoint of locomotion that is well-established in the literature (Rajini et al, 2008), we showed that C. elegans display reversible effects of paralysis following shock wave exposure

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Summary

Introduction

The increasing prevalence of blast-related mild traumatic brain injury (br-mTBI) has become a considerable health and economic issue (Hoge et al, 2008). Due to the variety of ways that the brain can be injured through blast exposure, damaging mechanisms can be defined by the injurious aspect of blast exposure. Secondary (penetrating objects), tertiary (bodily impact with other objects), and quaternary (e.g. crushing injuries from falling objects) blast effects are defined (DePalma et al, 2005; Scott et al, 2006). While injuries resulting from secondary, tertiary, and quaternary blast effects may be more straightforward in terms of diagnosis and prognosis, injuries resulting from primary blast effects are more difficult. There is still, little understanding of the mechanisms connecting initial trauma and expression of clinical br-mTBI symptoms, a limiting factor in the efficacy of br-mTBI protection and treatment

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