Traumatic brain injury (TBI) is a significant health care issue with approximately 500,000 hospital admissions. Although there has been much progress in understanding he pathological mechanisms associated with TBI, knowledge of the complex and varied biochemical, cellular and molecular cascades affecting the traumatized brain are poorly understood. However, recent advances by our laboratory and others have demonstrated important roles for two families of cysteine proteases, calpains and caspases, in mediating necrotic and/or apoptotic cell death after trauma. Recent development of in vitro models of various components of mechanical and biochemical insults relevant to TBE have provided efficient and powerful tools for dissociation of trauma induced stimuli and subsequent cellular responses.
The aim of this proposal is to examine the relative contributory roles of calpains and caspase-3 proteases in various in vitro models of necrosis or apoptosis and in models of mechanical cell injury, glutamate excitotoxicity , and oxygen/glucose deprivation in primary septo-hippocampal cell cultures. Importantly, preliminary work has demonstrated that calpains and caspase-3 proteases can be individually or concurrently activated depending on the mode and/or magnitude of the initiating stimulus. In addition, this work demonstrates the use of caspase-3 activation as a sensitive biochemical marker for detection of apoptosis that is independent of classically defined morphological apoptotic alterations It is thought that result of this research will advance an understanding of the varied pathological responses to cellular insult, and will provide a sound foundation for eventual use of therapeutic interventions in numerous disorders of the central nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
7F32NS010857-02
Application #
6192714
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (02))
Program Officer
Chiu, Arlene Y
Project Start
1999-08-01
Project End
Budget Start
1999-08-01
Budget End
2000-07-29
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Florida
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611