Intravenous mannitol does not increase blood-brain barrier permeability to inert dyes in the adult rat forebrain

Intravenous mannitol (IV-M) is widely administered in the clinic to lower intracranial pressure in patients with brain trauma and stroke. However, intracarotid arterial mannitol (ICA-M) is known to potently open the blood-brain barrier (BBB) to serum protein tracers such as the Evans blue dye (EBD). In this study, we aimed to determine the potential effect of IV-M on BBB permeability to EBD and a small molecular tracer sodium fluorescein dye (NaF). Rats received intravenous EBD/NaF injections, and after a 30-min equilibration time, they received mannitol (20%, 0.5 g/kg) through either route of administration. At 90 min after the mannitol injection, the rats were perfused to rid their circulations of the tracers, and the tracers extravasated into the brain parenchyma were measured by photospectrometry. As expected, ICA-M considerably increased EBD extravasation into the rat forebrain regions, including the motor cortex (P = 0.0069), the striatum (P = 0.0097), and the hippocampus (P = 0.0281; student's t-test). In marked contrast, IV-M exerted no effect on EBD extravasation into these forebrain regions. To increase the power of the IV-M study, we repeated the experiments in two independent trials of experiments (n=6-9/group/trial) and found the same result. Finally, consistent with no effect on EBD extravasation, IV-M had no effect on NaF extravasation into the rat forebrain. In conclusion, we report direct evidence that IV-M, at a dose used clinically, in contrast to the same dose of ICA-M, exerted no effect on BBB permeability to protein and small molecular tracers. NeuroReport 24:303-307 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.