Calcium Homeostasis Following Traumatic Neuronal Injury

John   T.   Weber

doi:10.2174/1567202043480134

Abstract

Cell death and dysfunction following traumatic brain injury (TBI) consists of a primary phase, which causes immediate consequences to cells by direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of insult. One of the major culprits that contributes to delayed neuronal damage and death after a traumatic insult is the calcium ion. The original calcium hypothesis suggests that a large, sustained influx of calcium into cells initiates cell death signalling cascades. While much of this original tenant remains true, recent findings suggest that the role of calcium in traumatic neuronal injury may be more complex. For example, a sustained level of intracellular free calcium is not necessarily lethal, but the specific route of calcium entry may couple calcium directly to cell death pathways. Other sources of calcium, such as intracellular calcium stores, can also cause cell damage. In addition, calcium-mediated signal transduction pathways have been found to be altered following injury. These alterations are sustained for several hours and may contribute to dysfunction in neurons that do not necessarily die after a traumatic episode. This review provides an overview of experimental evidence that has led to our current understanding of the role of calcium in neuronal death and dysfunction after TBI. While the focus is on alterations in neuronal calcium homeostasis following mechanical injury, these findings may have implications for other pathological states of the brain, such as ischaemia and neurodegenerative disease.

Keywords: calcium stores, excitotoxicity, neuronal death, trauma

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