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

Abstract 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. © 1995 Wiley‐Liss, Inc.