Lack of evidence for direct involvement of NMDA receptors or polyamines in blood-brain barrier injury after cerebral ischemia in rats.
It is hypothesized that after various types of brain injury, blood-brain barrier (BBB) opening and vasogenic edema result from excessive neuronal release of glutamate and stimulation of capillary N-methyl-d-aspartate (NMDA) receptors linked to polyamine (putrescine) synthesis in endothelial cells. We produced cerebral ischemia in rats and measured BBB opening 6 h later as the increase in regional transfer constants (Ki) for blood to brain diffusion of [3H]sucrose. Such BBB opening was not mitigated by drugs which block NMDA receptors (MK801 or AR-R 15896AR) or polyamine synthesis (difluoromethylornithine). These results question generality of the capillary NMDA receptor/polyamine hypothesis.
Preston
E
E
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada. ed.preston@nrc.ca
Webster
J
J
Palmer
G C
GC
D000818:Animals; D015317:Biogenic Polyamines / Q000096:biosynthesis / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D002545:Brain Ischemia / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D000518:Eflornithine / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D015317:Biogenic Polyamines; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D000518:Eflornithine