NMDA- 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 (NMDA; 100 nmol/μl) or endothelin-l (ET-1; 143 pmol/μl), significant increases in brain penetration of the highly polar, fluorescent tracer Lucifer yellow were observed. The competitive NMDA receptor antagonist selfotel (CGS-19755; 30 nmol/μl, i.c.) significantly reduced the NMDA-induced increases in blood-brain barrier permeability, but not those induced by ET-1. These results suggest that NMDA receptors can mediate 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 relationship between excitotoxicity and disruption of the blood-brain barrier, a major pathophysiological event in stroke and traumatic brain injury.