Application is made for a Teacher-Investigator Development Award on behalf of Dr. Chung Y. Hsu. Dr. Hsu has completed both research and clinical training and is pursuing an academic research and teaching career in clinical neuroscience. His major research activity will be investigating the involvement of arachidonate metabolites in vascular injury in the central nervous system using spinal cord injury as a model. This project encompasses two complementary approaches. First, the metabolism of arachidonic acid to thromboxane (TxA2) and prostacyclin (PGI2) will be studied in the experimental spinal cord injury model in order to determine whether the impact injury results in alteration of TxA2/PGI2 balance which may be important in maintaining vascular integrity and preventing thrombosis. Pharmacological manipulation of TxA2/PGI2 balance by exogenous PGI2 and thromboxane (Tx) synthetase inhibitors in spinal cord injury will also be studied. Secondly, techniques will be developed for assessing the thrombotic process in spinal cord injury using platelets labeled with radioactive indium (111In). The ultimate goal of this study is, using accumulation of 111In-labeled platelets as an index of thrombotic process, to explore the potential therapeutic role of PGI2 and Tx synthetase inhibitor in the reduction or prevention of thrombosis following spinal cord injury. Preliminary studies have shown (1) one hour following impact injury the ratio of the metabolites of TxA2 and PGI2 released from injured cord is shifted to a state more favorable of thrombosis; (2) 111In-labeled platelets accumulate at the site of injury and adjacent segments. This award will allow the applicant to devote 80% of his time to research and thus enable growth as an independent investigator. The additional research time will provide the applicant the opportunity to expand his research to include the vasogenic edema-another aspect of traumatic vascular injury which may be related to the formation of other arachidonate metabolites particularly leukotrienes.
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