Opening of the blood-brain barrier during isoflurane anaesthesia

In order to produce its desired effect, anaesthesia acts upon neuronal elements by modifying membrane conductances and transmitter interactions. The effect of higher doses of isoflurane, widely used in clinical settings, on the permeability of the blood-brain barrier (BBB) is meanwhile ignored. In this study we investigated the integrity of the BBB during various levels of isoflurane anaesthesia (1% and 3%) in cats by monitoring the extravasation of Evans blue. Simultaneously we measured the electroencephalogram (EEG), with particular emphasis on its direct current (DC) component. High doses of anaesthetic (3%) broke down the BBB in the cortex and thalamus, while milder doses (1%) only opened the BBB in the thalamus. The fluorescent signal of Evans blue was visible over an extravascular length of 23 mu m in the cortex and 25 mu m in the thalamus, similar to the diffusion of the same dye when the BBB was disrupted with mannitol. The opening of the BBB was associated with (i) a positive DC shift in the EEG measured on the scalp and (ii) an evaluated increase in cerebral volume of 2-2.8%. The opening of the BBB by high doses of isoflurane brings into discussion hitherto unexplored effects of anaesthesia on the brain. The electrophysiological correlate provided by the DC component of the EEG constitutes a promising option for the assessment of the BBB integrity during human anaesthesia.