MECHANISMS OF CALPAIN PROTEOLYSIS FOLLOWING TRAUMATIC BRAIN INJURY - IMPLICATIONS FOR PATHOLOGY AND THERAPY - A REVIEW AND UPDATE

Much recent research has focused on the pathological significance of c alcium accumulation in the central nervous system (CNS) following cere bral ischemia, spinal cord injury (SCI), and traumatic brain injury (T BI). Disturbances in neuronal calcium homeostasis may result in the ac tivation of several calcium-sensitive enzymes, including lipases, kina ses, phosphatases, and proteases. One potential pathogenic event in a number of acute CNS insults, including TBI, is the activation of the c alpains, calcium-activated intracellular proteases. This article revie ws new evidence indicating that overactivation of calpains plays a maj or role in the neurodegenerative cascade following TBI in vivo. Furthe r, this article presents an overview from in vivo and in vitro models of CNS injuries suggesting that administration of calpain inhibitors d uring the initial 24-h period following injury can attenuate injury-in duced derangements of neuronal structure and function. Lastly, this re view addresses the potential contribution of other proteases to neuron al damage following TBI.