Leakiness of rat brain microvessels to fluorescent probes following craniotomy

The effects of craniotomy and/or histamine treatment upon brain microvascular permeability was studied in Wistar rats. Extravasation of circulating Na-fluorescein (MW 376) and of FITC-albumin (MW 69,000) was observed through a cranial window using intravital fluorescence microscopy. Simple exposure of the pial microvessels induced formation of discrete spots of fluorescent material around venules, but not around arterioles or capillaries. The average number of leaky spots to Na-fluorescein and to FITC-albumin was 4.3 and 1.8 per 10 mm2, respectively, 35 min after exposure. Pretreatment of the rats with either indomethacin (a cyclo-oxygenase inhibitor) or promethazine (a histamine H1-receptor blocker) did not reduce the number of leaky sites, whereas pretreatment with a combination of the two drugs had a significant protective effect. Administration of histamine (10(-4) M) to the exposed brain surface for 5 min increased the number of leaky sites to Na-fluorescein and FITC-albumin 3.2 and 3.6 times, respectively. It is concluded that exposure of the brain surface induces release of histamine and cyclo-oxygenase metabolites, and that these inflammatory mediators elicit formation of leaky sites in brain venules.