Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 295, Issue 4, Pages R1099-R1108Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.90430.2008
Keywords
N-methyl-D-aspartate; blood-brain barrier; cerebrovascular reactivity; glutamate excitotoxicity; intracellular calcium
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Funding
- National Institutes of Health [HL-30260, HL-65380, HL-77731, HL-54176, HL-49373]
- National Scientific Research Fund of Hungary (OTKA) [K68976, K63401]
- National Bureau of Research and Development (NKTH) [RET-08/2004]
- Hungarian State Eotves Scholarship
- Hungarian Academy of Sciences
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Cerebral microvascular endothelial cells (CMVECs) have recently been implicated as targets of excitotoxic injury by L-glutamate (L-glut) or N-methyl-D-aspartate (NMDA) in vitro. However, high levels of L-glut do not compromise the function of the blood-brain barrier in vivo. We sought to determine whether primary cultures of rat and piglet CMVECs or cerebral microvascular pericytes (CMVPCs) are indeed sensitive to L-glut or NMDA. Viability was unaffected by 8-h exposure to 1 -10 mM L-glut or NMDA in CMVECs or CMVPCs isolated from both species. Furthermore, neither 1 mM L-glut nor NMDA augmented cell death induced by 12-h oxygen-glucose deprivation in rat CMVECs or by 8-h medium withdrawal in CMVPCs. Additionally, transendothelial electrical resistance of rat CMVEC-astrocyte cocultures or piglet CMVEC cultures were not compromised by up to 24-h exposure to 1 mML-glut or NMDA. The Ca2+ ionophore calcimycin (5 mu M), but not L-glut (1 mM), increased intracellular Ca2+ levels in rat CMVECs and CMVPCs assessed with fluo-4 AM fluorescence and confocal microscopy. CMVEC-dependent pial arteriolar vasodilation to hypercapnia and bradykinin was unaffected by intracarotid infusion of L-glut in anesthetized piglets by closed cranial window/intravital microscopy. We conclude that cerebral microvascular cells are insensitive and resistant to glutamatergic stimuli in accordance with their in vivo role as regulators of potentially neurotoxic amino acids across the blood-brain barrier.
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