Brain interstitial volume fraction and tortuosity in anoxia. Evaluation of the ion-selective micro-electrode method

The micro-electrode method for determination of interstitial volume fraction (alpha) (Nicholson & Phillips 1981), was evaluated. The extracellular marker, tetramethylammonium+, is iontophoretically ejected from a micropipette and the change in concentration measured at a distance by an ion-sensitive micro-electrode and fitted to a diffusion equation. We used suspensions of human red blood cells as a model system and found that the values of alpha determined by this method and by haematocrit measurement were linearly correlated (r = 0.94) and not significantly different. The micro-electrode method was used to characterize the interstitial space in rat brain cortex during normal conditions and during arrest of blood flow supply. Transport of solutes in interstitial space is governed by two characteristics, the interstitial volume fraction and the tortuosity factor. During control conditions, the interstitial volume fraction was 0.18 +/- 0.02 (mean +/- SEM), whereas it decreased to 0.07 +/- 0.01 in ischaemia. The tortuosity factor was 1.40 +/- 0.05 in controls and increased to 1.63 +/- 0.09 during ischaemia. Our measurements support the validity of the micro-electrode method (Nicholson & Phillips 1981) and demonstrate that arrest of blood supply changes interstitial diffusional characteristics of brain cortex mainly by diminishing the size of the interstitial diffusional space.