Date of Award

2020

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmacology and Experimental Therapeutics

Abstract

The restoration of blood flow to ischemic cerebral tissue can result in reperfusion injury, and blocking reperfusion injury can significantly aid in recovery of ischemic tissue. Bradykinin has been shown to exhibit protective effects, but does not reach protective levels during reperfusion due to inactivation by aminopeptidase P2 (APP2). Therefore, inhibiting APP2 during reperfusion is a potential therapeutic strategy to aid in the reduction of reperfusion injury, leading to the development of ST-115, an APP2 inhibitor. It was hypothesized that administration of ST-115 during ischemic stroke, and just prior to reperfusion, will result in reduced neurological injury and increased functional recovery in a rat transient middle cerebral artery occlusion model. Here, we report that ST-115 treatment five minutes prior to reperfusion reduces edema and inflammation and promotes functional recovery post-stroke, suggesting that inhibition of APP2 may be a viable pharmaceutical target for improving stroke outcomes.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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Pharmacology Commons

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