Opening of the blood-brain barrier during isoflurane anaesthesia

• Published in: The European journal of neuroscience Vol. 28; no. 7; pp. 1330 - 1341
• Main Authors: Tétrault, Samuel, Chever, Oana, Sik, Attila, Amzica, Florin
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2008
• Subjects: Anesthetics, Inhalation - adverse effects; Anesthetics, Inhalation - toxicity; Animals; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - physiopathology; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Brain Edema - chemically induced; Brain Edema - metabolism; Brain Edema - physiopathology; Cats; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Coloring Agents; coma; DC shift; Dose-Response Relationship, Drug; EEG; Electroencephalography - drug effects; Evans Blue; Evoked Potentials - drug effects; Evoked Potentials - physiology; Isoflurane - adverse effects; Isoflurane - toxicity; Nerve Degeneration - chemically induced; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neurons - drug effects; Neurons - metabolism; Thalamus - drug effects; Thalamus - metabolism; Thalamus - physiopathology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2008.06443.x

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 μm in the cortex and 25 μm 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.