Neuroglial Response to High-Amplitude, Short-Duration Pressure Transients in Monoculture

Abstract

Blast-induced traumatic brain injury (bTBI) was reported in 125,000 U.S. service men and women from 2000 to 2018. With no prophylactic treatments having been granted FDA approval, there is a clear need for further understanding of the impact of blasts on the central nervous system. The biological response of brain cells due to the near-instantaneous overpressure of blast onset remains unresolved. Laser-induced pressures isolate high-amplitude, short-duration pressure transients, similar to the initial peak of blast pressures. In this study, we uncover the effects of high-amplitude, short-duration pressure transients on monocultures of astrocytes, microglia, and neurons through intracellular calcium imaging, cell viability assays, and quantifying intracellular and extracellular immune signaling proteins. The results indicate that while all three cell types follow a similar activation curve for induced intracellular calcium transients, the downstream impact of high-amplitude, short-duration pressures on neurons and glia deviate. Neurons are particularly susceptible to non-reversible damage, while glia activates traditionally neuroprotective pathways rather than neurodegenerative pathways in response to high-amplitude, short-duration pressures. This work has important implications for developing countermeasures for bTBI with either the high-frequency component of a blast wave or the effects of that component being potential targets for prevention.