Quantitative Analysis Of Cellular and Paracellular Effects Involved in Disruption of the Blood-Brain Barrier of an Insect by Hypertonic Urea

Brief exposure of central nervous connectives of the cockroach, Periplaneta americana, to 3 M-urea, a treatment known to increase the leak of cations across the blood-brain barrier system, caused a reduction in the resistance and potential difference (p.d.) across the perineurium, which forms the principal component of the barrier. There was also a reduction in the p.d. across the apical membrane of perineurial cells which might indicate a higher interstitial potassium level. There was no effect upon the p.d. recorded across the basolateral membrane of the cells, but there was some reduction in the ratio between the resistances of the basolateral and apical membranes. When the potassium level in the saline was raised, the depolarization of the basolateral membrane was less reduced by urea than the change in p.d. across the perineurium. During high K, the gradual depolarization of the perineurial membranes was speeded by urea treatment, as was the change in axon resting potential, as to be expected with more rapid entry of K into the interstitial system. Analysis of the initial effects of high K upon the electrical characteristics of the perineurium indicated that urea had reduced the resistance of the paracellular pathway by 73% and the resistance of the basolateral membrane by 44%. Most of the electrical events in urea-treated preparations could be simulated from the estimated parameters and an estimation of the rise in interstitial K level during the high K exposure. The study indicates that the increased leak across the perineurium caused by urea treatment results chiefly from a decrease in intercellular restriction.