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) The number of papers acquired via PubMed for the search term “neuroprotective” plotted verses the year. (B) A log transform of the plot in A where “years” is now expressed as the number of years with 1986 starting as year 1.
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brainsci-03-00460-f001: (A) The number of papers acquired via PubMed for the search term “neuroprotective” plotted verses the year. (B) A log transform of the plot in A where “years” is now expressed as the number of years with 1986 starting as year 1.

Mentions: The earliest paper on PubMed using the term “neuroprotective” was a 1986 Stroke paper by Silverstein et al. showing the calcium antagonist flunarizine protected against hypoxia-ischemia brain damage in immature rats [2]. A PubMed search of the term “neuroprotective” gave 30,815 papers between 1986 and 2011. A plot of the number of papers by year shows the rapid increase in papers (Figure 1A) that, when plotted on a log-log axis reveals a power law increase with exponent 2.6, and a correlation coefficient =0.988 (Figure 1B). Thus, we see a mathematical expression describing the accumulation of papers about neuroprotection over the previous 26 years.


A program for solving the brain ischemia problem.

DeGracia DJ - Brain Sci (2013)

(A) The number of papers acquired via PubMed for the search term “neuroprotective” plotted verses the year. (B) A log transform of the plot in A where “years” is now expressed as the number of years with 1986 starting as year 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

brainsci-03-00460-f001: (A) The number of papers acquired via PubMed for the search term “neuroprotective” plotted verses the year. (B) A log transform of the plot in A where “years” is now expressed as the number of years with 1986 starting as year 1.
Mentions: The earliest paper on PubMed using the term “neuroprotective” was a 1986 Stroke paper by Silverstein et al. showing the calcium antagonist flunarizine protected against hypoxia-ischemia brain damage in immature rats [2]. A PubMed search of the term “neuroprotective” gave 30,815 papers between 1986 and 2011. A plot of the number of papers by year shows the rapid increase in papers (Figure 1A) that, when plotted on a log-log axis reveals a power law increase with exponent 2.6, and a correlation coefficient =0.988 (Figure 1B). Thus, we see a mathematical expression describing the accumulation of papers about neuroprotection over the previous 26 years.

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