Estimating The Variables Of The Nonlinear Dynamical Theory Of Acute Cell Injury

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