Proteolytic Mechanisms of cell Death Following Traumatic Brain Injury
Abstract
Activation of calpains and caspases are major pathological events in traumatic brain injury (TBI). This proposal addresses four hypotheses: (1) TBI produces early and sustained increases in calpain and caspae-3 activity that vary depending upon the brain regions studies. (2) TBI can produce differential activation of calpain isoforms (mu-calpain, m-calpain) in different regions, and changes in calpain activity may be differentially localized in subcellular fractions (cytosolic vs. membrane). (3) TBI produces changes in calpastatin mRNA and differential expression of calpastatin isoforms in different brain regions. Changes may be differentially localized in subcellular fractions. (4) Increased magnitudes and duration of calpain and caspae-3 activation following TBI are predictive of morphopathology including focal contusion as well as necrotic and apoptotic cell death. Morphopathological changes, including apoptotic and necrotic cell death, can occur in regions showing activation of calpain but not caspase 3-like proteases. Recent technical advances have enhanced opportunities to study mechanisms of calpain and caspse-3 proteolysis in TBI, and the proposed research will refine powerful new methods.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA385935
Entities
People
- Ronald L. Hayes
Organizations
- University of Florida