Shock Waves Simulating Blast-Induced Traumatic Brain Injury Activate Purinergic Signaling in Astrocytes

Abstract

While progress has been made in physically protecting individuals from experiencing bTBI, there are no countermeasures or drug treatments to ameliorate the effects of bTBI after exposure. Historically bTBI research focused on neuronal protection and the effect of neuronal trauma with less attention to the effect of injury to astrocytes. We have developed a pneumatic device that delivers shockwaves, similar to those known to induce bTBI, within a chamber optimal for fluorescence microscopy. Abrupt changes in pressure can be created with and without the presence of shear forces at the surface of cells. We discovered that exposure of primary cultures of human central nervous system cells to these transient peak pressures per se do not cause cellular excitation. Instead, it is the concomitant shear forces that reproducibly activate the cells. The resultant calcium signal is amplified and spread by cell-cell propagation arising from a small number of cells that are directly affected by the shear forces (Ravin et.al 2012). Astrocytes have long-range calcium signaling systems that propagate as calcium waves instead of action potentials and modulate neuronal and CNS activity. Blast shock waves simulating those initiating primary bTBI cause a cascade of events in human CNS dissociated cultures in which calcium is elevated mainly in astrocytes, leading to a propagation of calcium waves throughout the network, mediated by ATP signaling. We found that P2 receptor antagonists are able to reduce this response suggesting a potential therapeutic target for treating TBI.