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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/R1099    most recent 90430.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Domoki, F. Articles by Busija, D. W. PubMed PubMed Citation Articles by Domoki, F. Articles by Busija, D. W.

RECEPTORS AND SIGNALING PATHWAYS

Cerebromicrovascular endothelial cells are resistant to L-glutamate

¹Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina; ²Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary; and ³Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Submitted 17 May 2008 ; accepted in final form 27 July 2008

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 mM L-glut or NMDA. The Ca²⁺ ionophore calcimycin (5 µM), 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.

N-methyl-D-aspartate; blood-brain barrier; cerebrovascular reactivity; glutamate excitotoxicity; intracellular calcium