NMDA-INDUCED AND ENDOTHELIN-1-INDUCED INCREASES IN BLOOD-BRAIN-BARRIER PERMEABILITY QUANTITATED WITH LUCIFER YELLOW

At 48 h following intrastriatal injection of N-methyl-D-aspartate (NMD A; 100 nmol/mu l) or endothelin-1 (ET-1; 143 pmol/mu l), significant i ncreases in brain penetration of the highly polar, fluorescent tracer Lucifer yellow were observed. The competitive NMDA receptor antagonist selfotel (CGS-19755; 30 nmol/mu l, i.c.) significantly reduced the NM DA-induced increases in blood-brain barrier permeability, but not thos e induced by ET-1. These results suggest that NMDA receptors can media te increases in blood-brain barrier permeability but do not primarily mediate increases in blood-brain barrier permeability caused by ET-1. This is the first study to our knowledge investigating the relationshi p between excitotoxicity and disruption of the blood-brain barrier, a major pathophysiological event in stroke and traumatic brain injury.