Designing in vivo concentration gradients with discrete controlled release: a computational model

J Neural Eng. 2010 Aug;7(4):046013. doi: 10.1088/1741-2560/7/4/046013. Epub 2010 Jul 19.


One promising neurorehabilitation therapy involves presenting neurotrophins directly into the brain to induce growth of new neural connections. The precise control of neurotrophin concentration gradients deep within neural tissue that would be necessary for such a therapy is not currently possible, however. Here we evaluate the theoretical potential of a novel method of drug delivery, discrete controlled release (DCR), to control effective neurotrophin concentration gradients in an isotropic region of neocortex. We do so by constructing computational models of neurotrophin concentration profiles resulting from discrete release locations into the cortex and then optimizing their design for uniform concentration gradients. The resulting model indicates that by rationally selecting initial neurotrophin concentrations for drug-releasing electrode coatings in a square 16-electrode array, nearly uniform concentration gradients (i.e. planar concentration profiles) from one edge of the electrode array to the other should be obtainable. DCR therefore represents a promising new method of precisely directing neuronal growth in vivo over a wider spatial profile than would be possible with single release points.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain Chemistry*
  • Computer Simulation
  • Delayed-Action Preparations / chemistry*
  • Delayed-Action Preparations / radiation effects*
  • Drug Compounding / methods
  • Humans
  • Models, Chemical*
  • Nerve Growth Factors / administration & dosage*
  • Nerve Growth Factors / chemistry*
  • Nerve Growth Factors / radiation effects


  • Delayed-Action Preparations
  • Nerve Growth Factors