This research proposal is a re-submission of a research project that was submitted as a competitive renewal. The long-term objective of this research proposal is to evaluate and understand potential pharmacotherapies for acute cerebral ischemia so that appropriate drugs might be tested which will reduce or prevent calcium entry into neurons or its consequences. Therapies that will be directed at this will include selected calcium channel blockers, competitive and non-competitive glutamate antagonists, phospholipase antagonists, and possibly newer agents which may act on glycine or sigma sites. Outcome measures will include mortality, light microscopic measurement of ischemic damage, and learning ability. Mechanisms of action of each pharmacotherapy will be determined by cerebral blood flow, immunocytochemical localization and quantitation of calcium calmodulin binding and assessment of CaM-kinase II activity. The second major goal of this research is to expand previous studies of calcium calmodulin binding after global ischemia to better understand calcium activated events in determining irreversible neuronal injury. Studies will be designed to correlate calcium calmodulin binding studies with CaM Kinase II activity and explore the behavior of this kinase after various ischemic intervals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023979-06
Application #
2265034
Study Section
Neurology A Study Section (NEUA)
Project Start
1987-07-01
Project End
1994-12-31
Budget Start
1993-04-01
Budget End
1994-12-31
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
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Zhao, Xiurong; Liu, Shi-Jie; Zhang, Jie et al. (2005) Combining insulin-like growth factor derivatives plus caffeinol produces robust neuroprotection after stroke in rats. Stroke 36:129-34

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