CAPILLARY NMDA RECEPTORS REGULATE BLOOD-BRAIN-BARRIER FUNCTION AND BREAKDOWN

Polyamines and their regulatory synthetic enzyme ornithine decarboxylase (ODC) have been implicated in blood-brain barrier (BBB) breakdown following cryogenic injury. ODC activation and BBB breakdown are prevented by MK-801, indicating involvement of NMDA receptors. Studies in isolated rat cerebral capillaries supports the presence of NMDA receptors linked to ODC. NMDA (1-50-mu-M) stimulated capillary uptake of horseradish peroxidase, 2-deoxy-[C-14]glucose, and Ca-45 in a receptor-, concentration-, polyamine- and Ca 2--dependent manner. We suggest that NMDA receptors may couple capillary transport of nutrients to glutamate-mediated neuronal excitation, and when overstimulated disrupt normal BBB function.