Abstract
BACKGROUND: Military and law enforcement personnel are routinely exposed to shock waves from weapon systems and explosive devices during training and operations. Even when such shock wave exposure results in mild traumatic brain injury (mTBI) without abnormalities on routine imaging, persistent neurological symptoms may occur. Yet, the biological processes that link an acute blast wave insult to progressive neuronal dysfunction remain poorly defined. METHODS: We established Caenorhabditis elegans nematodes as a genetically accessible animal model for blast-related mTBI (br-mTBI). Animals were exposed in gelatin to shock waves generated by a custom-built shock wave generator (SWG), which produces explosive shock waves with an abrupt overpressure peak followed by a negative pressure phase. The resulting pressure-time curves are very similar to the profiles of conventional explosives in free-field setups. To enable mechanistic studies under controlled laboratory conditions, we developed a complementary platform using a medical radial extracorporeal shock wave therapy (rESWT) device. Motor behavior, mechanosensory function, neuronal morphology and cytoskeletal integrity were analyzed during aging. RESULTS: SWG-derived shock waves induced immediate but reversible motor and sensory deficits, followed by an accelerated age-dependent decline in movement and touch sensitivity. The rESWT platform accurately reproduced these phenotypes. Touch receptor neurons showed progressive structural abnormalities, including degeneration, alongside acute PTL-1/Tau mislocalization consistent with cytoskeletal injury. CONCLUSIONS: Defined shock wave exposure is sufficient to provoke long-term neuronal functional decline in C. elegans, accompanied by structural deterioration and premature neurodegeneration. This tractable model enables lifelong phenotyping and mechanistic dissection of how an acute shock wave insult progresses to chronic neuronal dysfunction, and provides a scalable platform for identifying molecular and pharmacological modifiers that promote resilience.