Post-ischemic administration of HU-211, a novel non-competitive 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 (406 +/- 19 vs. 539 +/- 33 micrograms/g, mean +/- S.E.M.) as well as other sites of the affected hemisphere (866 +/- 68 vs. 1096 +/- 68 micrograms/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.
Belayev
L
L
Department of Neurology, University of Miami School of Medicine, FL 33101, USA.
Busto
R
R
Watson
B D
BD
Ginsberg
M D
MD
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy*; D002544:Cerebral Infarction / Q000188:drug therapy*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013997:Time Factors
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013759:Dronabinol; C062018:HU 211