Proteolytic Mechanisms of Cell Death Following Traumatic Brain Injury
Abstract
We have examined the pathological significance of calcium accumulation in the central nervous system (CNS) following a variety of insults including cerebral ischemia, spinal cord and traumatic brain injury (TBI). This research has been motivated by recognition that disturbances in neuronal calcium homeostasis can result in activation of several calcium sensitive enzymes including lipases, kinases, phosphatases and, importantly, proteases. Recent studies have provided strong evidence that activation of the calpains, calcium activated intracellular proteases, is a major pathological event in a number of acute CNS injuries including TBI. In addition to calpains, other data have implicated another important family of cysteine proteases, caspases. Caspase-3 is an effector caspase especially important to caspase mediated pathology. Western blot immunoassays of calpain and caspase-3 specific breakdown products proposed in SOW 1 provided an efficient means of determining which brain regions and time points were most usefully incorporated into studies of SOW 2 which provided more detailed information on mechanisms of calpain activation. SOW 3 focused on endogenous modulation of proteolytic activity, including the enzyme calpastatin. SOW 4 addressed the task of providing more direct evidence of the pathological significance of activation of calpains and caspases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA431322
Entities
People
- Ronald L. Hayes
Organizations
- University of Florida