Limits...
A program for solving the brain ischemia problem.

DeGracia DJ - Brain Sci (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Wayne State University, 4116 Scott Hall, 540 E. Canfield, Detroit, MI 48201, USA. ddegraci@med.wayne.edu.

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.

No MeSH data available.


Related in: MedlinePlus

A plot of cS vs. 1/λS with hypothetical values for a CA1 pyramidal neuron (CA1), a dentate gyrus granule neuron (DG), a brainstem motorneuron (BS) and a skeletal muscle myocyte. The labels at each vertex indicate the qualitative interpretation of the relative parameter values.
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brainsci-03-00460-f004: A plot of cS vs. 1/λS with hypothetical values for a CA1 pyramidal neuron (CA1), a dentate gyrus granule neuron (DG), a brainstem motorneuron (BS) and a skeletal muscle myocyte. The labels at each vertex indicate the qualitative interpretation of the relative parameter values.

Mentions: It is only one additional step to imagine converting the nonparametric ranking of ischemic susceptibility into specific numerical values. Applying these ideas to brain ischemia, we should consider each cell type in the brain as a point on a plane whose axes are cS and 1/λS (Figure 4). The CA1 pyramidal neuron is the weakest of all the neuron types with respect to ischemic injury so it has the lowest value of cS. A dentate granule neuron is stronger than a CA1 neuron and will have a higher value of cS. A brainstem neuron is stronger still and will have a greater value of cS. However, in comparison to a skeletal muscle myocyte, the three neuron types will have relatively closer values of cS, and the myocyte will have a value for cS outside the range of the neuron types. These are illustrated in Figure 4, with similar relative relationships given for 1/λS. Because the following examples will focus only on one cell type, both cS and λS will be true constants in the exercises performed in this paper.


A program for solving the brain ischemia problem.

DeGracia DJ - Brain Sci (2013)

A plot of cS vs. 1/λS with hypothetical values for a CA1 pyramidal neuron (CA1), a dentate gyrus granule neuron (DG), a brainstem motorneuron (BS) and a skeletal muscle myocyte. The labels at each vertex indicate the qualitative interpretation of the relative parameter values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061849&req=5

brainsci-03-00460-f004: A plot of cS vs. 1/λS with hypothetical values for a CA1 pyramidal neuron (CA1), a dentate gyrus granule neuron (DG), a brainstem motorneuron (BS) and a skeletal muscle myocyte. The labels at each vertex indicate the qualitative interpretation of the relative parameter values.
Mentions: It is only one additional step to imagine converting the nonparametric ranking of ischemic susceptibility into specific numerical values. Applying these ideas to brain ischemia, we should consider each cell type in the brain as a point on a plane whose axes are cS and 1/λS (Figure 4). The CA1 pyramidal neuron is the weakest of all the neuron types with respect to ischemic injury so it has the lowest value of cS. A dentate granule neuron is stronger than a CA1 neuron and will have a higher value of cS. A brainstem neuron is stronger still and will have a greater value of cS. However, in comparison to a skeletal muscle myocyte, the three neuron types will have relatively closer values of cS, and the myocyte will have a value for cS outside the range of the neuron types. These are illustrated in Figure 4, with similar relative relationships given for 1/λS. Because the following examples will focus only on one cell type, both cS and λS will be true constants in the exercises performed in this paper.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Wayne State University, 4116 Scott Hall, 540 E. Canfield, Detroit, MI 48201, USA. ddegraci@med.wayne.edu.

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.

No MeSH data available.


Related in: MedlinePlus