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Access Type

WSU Access

Date of Award

January 2017

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Physiology

First Advisor

Donald J. DeGracia

Abstract

This Dissertation is the first to estimate the variables D and S of the nonlinear theory of acute cell injury in hippocampal regions CA1 and CA3 using a rat model of global brain ischemia and reperfusion (I/R). D was estimated by quantifying protein aggregates using ubiquitin Western blotting. S was estimated by quantifying changes in polysomal mRNAs as measured by microarray chips. D and S time courses were sampled at 0.5, 8, 16, 24, 48, and 72 hrs of reperfusion after 10 min brain ischemia. CA1 dies and CA3 survives. The theory predicts D will be larger in CA1 and S in CA3. Area under the curves of the D and S time courses showed this to be true. Trajectories of D vs S qualitatively matched updated versions of the theory. However, quantitative fits gave nonlinear correlation coefficients in the range 0.7-0.8. It was concluded that the acquired data did not falsify the theory. However, inadequate sampling over the time course, and the underestimation of S by failing to account for non-transcription dependent stress responses prevented strong quantitative fits between the measured estimates of D and S and theoretical time courses.

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