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A Program for Solving the Brain Ischemia Problem
Department of Physiology, Wayne State University, 4116 Scott Hall, 540 E. Canfield, Detroit, MI 48201, USA
Received: 15 January 2013; in revised form: 23 March 2013 / Accepted: 26 March 2013 / Published: 8 April 2013
Abstract: Our recently described nonlinear dynamical model of cell injury is here applied to the problems of brain ischemia and neuroprotection. We discuss measurement of global brain ischemia injury dynamics by time course analysis. Solutions to proposed experiments are simulated using hypothetical values for the model parameters. The solutions solve the global brain ischemia problem in terms of “master bifurcation diagrams” that show all possible outcomes for arbitrary durations of all lethal cerebral blood flow (CBF) decrements. The global ischemia master bifurcation diagrams: (1) can map to a single focal ischemia insult, and (2) reveal all CBF decrements susceptible to neuroprotection. We simulate measuring a neuroprotectant by time course analysis, which revealed emergent nonlinear effects that set dynamical limits on neuroprotection. Using over-simplified stroke geometry, we calculate a theoretical maximum protection of approximately 50% recovery. We also calculate what is likely to be obtained in practice and obtain 38% recovery; a number close to that often reported in the literature. The hypothetical examples studied here illustrate the use of the nonlinear cell injury model as a fresh avenue of approach that has the potential, not only to solve the brain ischemia problem, but also to advance the technology of neuroprotection.
Keywords: brain ischemia; neuroprotection; nonlinear dynamics; bistability; cell injury
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DeGracia, D.J. A Program for Solving the Brain Ischemia Problem. Brain Sci. 2013, 3, 460-503.
DeGracia DJ. A Program for Solving the Brain Ischemia Problem. Brain Sciences. 2013; 3(2):460-503.
DeGracia, Donald J. 2013. "A Program for Solving the Brain Ischemia Problem." Brain Sci. 3, no. 2: 460-503.