Critical volume of rat cortex and extracellular threshold concentration for a pentylenetetrazol-induced epileptic focus

The initiation of focal interictal epileptiform activity (FIEA) has been shown to depend on the activation of a sufficiently large volume of brain tissue. We estimated the size of this `critical volume' for the convulsant pentylenetetrazol (PTZ) by analyzing the diffusion following its microinjection into rat motor cortex. PTZ concentration was monitored 100–200 μm away from the injection site with a PTZ-sensitive microelectrode. Diffusion analysis in 0.3% agar yielded the free diffusion coefficient D (8.50±0.15×10 −6 cm 2·s −1 at 37°C, median±S.E.M.). In brain tissue, diffusion was modified by extracellular volume fraction ( α), tortuosity ( λ=( D/ ADC) 1/2; ADC=apparent diffusion coefficient) and non-specific uptake ( k′). Using a value of 0.2 for α from previous studies, we found values of λ=1.61±0.01, k′=3.37±0.15×10 −3 s −1 and an injected volume U of 5.16±0.45×10 −10 l for pulses without FIEA, and λ=1.95±0.06, k′=6.24±1.73×10 −3 s −1 and U=7.40±0.66×10 −10 l for pulses with FIEA. From the calculated concentration distribution of PTZ during FIEA we estimated a threshold concentration of about 1.77 mM PTZ and a volume with a radius of about 219 μm in which this concentration had to be exceeded. Since this critical volume was comparable in size to foci elicited by penicillin or electric stimuli in previous studies, it is concluded that it is determined by intrinsic tissue properties rather than by the convulsive agent being used. © 1997 Elsevier Science B.V. All rights reserved.