Regulation of rCBF by diffusible signals: An analysis of constraints on diffusion and elimination

Local changes in cerebral hemodynamics are observed within a few hundred milliseconds of changes in neural activity. If hemodynamic responses are mediated by passive diffusion of a spatial signal (from the site of neural activity to the microvessels) then the dynamics of the response suggest a lower limit on the signal's apparent diffusion and elimination. The aim of this work was to estimate these limits and narrow the field of possible candidate substances. A simple biophysical simulation was used to examine how the time course of concentration changes in a spatial signal, at the site of action (microvessels), depends on key diffusion parameters (source geometry, apparent diffusion and elimination half-life). The simulations suggested 1) that the rise in signal concentration is mostly a function of source geometry and diffusion. Conversely falls in concentration depend on elimination and 2) even when sources are very sparsely distributed Nitric Oxide would have a sufficiently fast diffusion and elimination to signal the early components of activity-dependent hemodynamic response by passive diffusion. (C) 1995 Wiley-Liss, Inc.