POSTISCHEMIC ADMINISTRATION OF HU-211, A NOVEL NONCOMPETITIVE NMDA ANTAGONIST, PROTECTS AGAINST BLOOD-BRAIN-BARRIER DISRUPTION IN PHOTOCHEMICAL CORTICAL INFARCTION IN RATS - A QUANTITATIVE STUDY

We examined the effect of HU-211, a synthetic non-psychotropic cannabinoid with non-competitive N-methyl-D-aspartate (NMDA) antagonist properties, on blood-brain barrier (BBB) integrity after photochemically induced cortical infarction. Evans blue dye was used as a BBB permeability indicator after unilateral thrombotic cortical infarction was produced photochemically by 560 nm light irradiation of the cortex in male Wistar rats receiving rose bengal intravenously. HU-211 was injected in a dose of 4 mg/kg i.v. 30 min after stroke. Fluorometric measurement of Evans blue was performed 24 h later in six brain regions. Treatment with HU-211 significantly decreased extravasation of dye into the area of infarct (405 +/- 19 vs. 539 +/- 33 mu g/g, mean +/- S.E.M.) as well as other sites of the affected hemisphere (866 +/- 68 vs. 1096 +/- 68 mu g/g) compared to the vehicle group. These data indicate that HU-211 is an effective drug in protecting against the effects of focal ischemia-induced BBB disruption in the rat and suggest that the drug may be an effective treatment against the ischemic cell death and BBB disruption that can occur clinically following a stroke or cardiac arrest.