Blast traumatic brain injury (bTBI) has now been identified to associate with adverse health consequences among combat veterans. Post-traumatic stress disorder linked with explosive blasts, for example, may result from such brain injury. The fundamental questions about the nature, diagnosis, and long-term consequences of bTBI and causative relationship to post-traumatic stress disorder remain elusive, however. A better understanding of brain tissue injury requires elucidation of potential mechanisms. One such mechanism may be generation of microcavitation bubbles in the brain after an explosive blast and their subsequent interaction with brain cells. Using a controlled electrical discharge system, we have successfully generated shock waves (∼10 MPa) and microbubbles (20-30 μm) in the cell culture of mouse astrocytes. Detachment of astrocytes from the substrate after exposure to microbubbles was observed, and it depended on repetitive exposures. Of the cells that survived the initial assault, several subcellular changes were monitored and determined using fluorescent microscopy, including cell viability, cytoskeletal reorganization, changes in focal adhesion, membrane permeability, and potential onset of apoptosis. While the astrocytes impacted by the shock wave only demonstrated essentially unaltered cellular behavior, the astrocytes exposed to microbubbles exhibited significantly different responses, including production of reactive oxygen species by collapse of microbubbles. In the present study, we characterized and report for the first time the altered biophysical and subcellular properties in astrocytes in response to exposure to the combination of shock waves and microbubbles.
Blast-induced traumatic brain injury (bTBI) is a neurological dysfunction that can result from a sudden exposure to shockwave and lead to adverse health consequences. Currently, there are no preventive measures that specifically target bTBI. Several hypotheses have been formulated to explain such injuries, including the generation of microcavitation (e.g., microbubbles) in the brain that subsequently collapses with high pressure. This study was designed to explore and elucidate potential therapeutic effects of surfactants (poloxamers P188) to partially repair the damaged brain tissue due to bTBI. A controlled electrical discharge system was designed and validated to generate microbubbles of 20-30 μm in size. Using this system, we tested the hypothesis that the P188 can partially rescue astrocytes exposed to collapsing microbubbles. The immediate impact of the collapse of microbubbles created a crater-like region in which astrocytes detached from the substrate. Of those cells that survived the initial mechanical assault, the poloxamer P188 demonstrated reparative potential by partially restoring calcium spiking and minimizing the production of reactive oxygen species. The FDA-approved P188 may offer a potential therapeutic treatment for those exposed to a blast and suffered bTBI.
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