Increased permeability of the blood-brain barrier (BBB) is a prominent feature of multiple sclerosis (MS). However, the cause of the BBB leak and its role in the pathogenesis of MS are unknown. The present study addressed these questions in the Semliki Forest virus (SFV) model of MS in optic nerves of Balb/C mice, using the unidirectional transfer coefficient for [C-14]mannitol as a measurement of BBB permeability and immunolabelling with anti-myelin basic protein (MBP) to determine the time-course and extent of demyelination. In SFV, there was a significant increase in BBB permeability in the optic nerve, prior to the onset of demyelination. The BBB leak was blocked by treatment with cimetidine, an antihistamine which acts on H-2 receptors at the BBB. Preliminary results suggested that cimetidine may also have delayed the onset or reduced the level of demyelination in the optic nerve. The results support a role for histamine in BBB leak in the SFV mouse model of MS and indicate that BBB leak may be integral to the pathogenesis of demyelination.

We have measured blood-brain barrier permeability changes during Semliki Forest Virus infections in the Balb/c mouse, and shown that the permeability changes have a biphasic response peaking at post inoculation days 5 and 14. The histamine H-2 receptor antagonist, cimetidine reduced the permeability changes al post inoculation day 5.