Alterations in calcium-mediated signal transduction after traumatic injury of cortical neurons

Calcium influx and elevation of intracellular free calcium ([Ca2+](i)), with subsequent activation of degradative enzymes, is hypothesized to cause cell injury and death after traumatic brain injury. We examined the effects of mild-to-severe stretch-induced traumatic injury on [Ca2+](i) dynamics in cortical neurons cultured on silastic membranes. [Ca2+](i) was rapidly elevated after injury, however, the increase was transient with neuronal [Ca2+](i) returning to basal levels by 3 h after injury, except in the most severely injured cells. Despite a return of [Ca2+](i) to basal levels, there were persistent alterations in calcium-mediated signal transduction through 24 h after injury. [Ca2+](i) elevation in response to glutamate or NMDA was enhanced after injury. We also found novel alterations in intracellular calcium store-mediated signaling. Neuronal calcium stores failed to respond to a stimulus 15 min after injury and exhibited potentiated responses to stimuli at 3 and 24 h post-injury. Thus, changes in calcium-mediated cellular signaling may contribute to the pathology that is observed after traumatic brain injury. (C) Harcourt Publishers Ltd 1999.