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/microliter) or endothelin-1 (ET-1; 143 pmol/microliter), 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/microliter, 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.
Miller
R D
RD
Department of Neurosurgery, Medical College of Pennsylvania, Philadelphia, USA.
Monsul
N T
NT
Vender
J R
JR
Lehmann
J C
JC
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D016232:Endothelins / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D007546:Isoquinolines; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D016232:Endothelins; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D007546:Isoquinolines; D010875:Pipecolic Acids; C053672:selfotel; D016202:N-Methylaspartate; C017475:lucifer yellow