Since many strokes are caused by cerebrovascular thrombosis or embolism, thrombolytic therapy is felt to be a promising pharmacological stroke treatment. This study has developed a series of coordinated models of embolic stroke that are specifically designed to permit the determination of which pharmacological strategies may improve neurological function. The methods allow an estimation of the frequency and severity of complications that may be encountered. Experiments presented are designed to determine the relevant efficacy and safety of tPA, urokinase, or acylated plasminogen-streptokinase-activator complex. Experiments will also test the best thrombolytic agent in combination with drugs that are felt to have neuroprotective properties. These drugs include glutamate antagonists and a serotonin antagonist with calcium channel blocking actions. There is also reason to suspect that leukocytes increase damage after clot lysis by plugging the microvascular or other toxic effects. Cell surface antigens on the leukocytes or the vascular endothelial cells may be involved in this process. Antibodies to the surface antigens are available and preliminary data indicates that they may reduce neurological damage. The studies are proposed to test the antibodies in conjunction with thrombolytic therapy. These studies should help identify more effective forms of therapy as a basis for future clinical trials.
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