Region‐, dose‐, and state‐dependency of isoflurane‐induced changes in blood‐brain barrier permeability

Abstract

Isoflurane opens the blood‐brain barrier (BBB) to inert tracers like Evans blue dye (EBD). However, the dose‐ and the region‐specificity are not known. To avoid confounding effect of anesthesia per se, the conventional protocol has been to subject the laboratory animal to another pre‐existing anesthesia. Here, 1% isoflurane increased EBD extravasation into the prefrontal cortex (PFC), the motor cortex (MC), the striatum (ST), the cerebellum (CE), and the liver of urethane‐anesthetized rats, but had no effect on blood EBD concentration. In marked contrast, 2% isoflurane had no effect on EBD extravasation to central and peripheral tissues, but increased blood EBD concentration. Because pre‐existing anesthesia can compromise the cardiovascular system, we repeated the study in otherwise‐conscious rats. Surprisingly, not only did isoflurane had no effect on EBD extravasation into the MC, the ST, and the CE, it decreased EBD extravasation into the PFC and the liver. The effect of isoflurane in these otherwise‐conscious rats could not be due to alleviation of stress, as there was little noticeable difference between EBD extravasation in rats placed in home cage, rats placed in the anesthetic cage, and rats placed in the anesthetic cage filled with the gaseous vehicle. In summary, isoflurane‐induced changes in BBB was region‐specific, dose‐dependent, and reversed by pre‐existing anesthesia. (Supported by Taiwan NSC)