Cellular Reparative Effects of Poloxamer P188 in Blunt Force Trauma to Brain Tissue

Blast–induced traumatic brain injury (bTBI) is a neurological dysfunction that can result from a sudden exposure to blunt force and leading to adverse health consequences. Currently, there are no treatment or preventive measures that specifically target TBI. Several hypotheses have been formulated to explain such injury, including the generation of microcavitation (e.g., microbubbles) in the brain that subsequently collapses with high pressure causing both physically and biochemically adverse effects. 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 to 30 µm in size. Using this system, we tested the hypothesis that triblock surfactants poloxamers can partially rescue astrocytes exposed to collapse of microbubbles. Immediate impact of collapse of microbubbles was to create a crater-like region in which the cells detached from the substrate. Of the cells that survived the initial mechanical insult at the periphery of the crater, we monitored the calcium dynamics and production of reactive oxygen species (ROS) using fluorescence microscopy. Based on our results, we report the poloxamers are capable of rescuing partially damaged astrocytes and restore the cellular functionality. P188 has been shown to seal the damaged cell membrane and facilitate to recover the membrane integrity. Since P188 is FDA-approved, the polymeric compounds may offer a potential therapeutic treatment for those exposed to blunt force trauma.