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Lack of glutamate excitotoxicity in primary rat and piglet cerebromicrovascular endothelial cell cultures
Author(s) -
Domoki Ferenc,
Kis Béla,
Gáspár Tamás,
Bari Ferenc,
Busija David W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.734.5
Subject(s) - excitotoxicity , nmda receptor , glutamate receptor , glutamatergic , in vivo , in vitro , intracellular , chemistry , blood–brain barrier , vasodilation , endocrinology , medicine , pharmacology , biology , central nervous system , biochemistry , receptor , microbiology and biotechnology
Cerebromicrovascular endothelial cells (CMVECs) have recently been claimed to be vulnerable to excitotoxic levels of L‐glutamate (L‐glut) normally present in the blood plasma, and be involved in L‐glut‐induced vasodilation. Our purpose was to clarify the effects of L‐glut and N‐methyl‐ D ‐aspartate (NMDA) on CMVECs of two species. Primary CMVEC cultures were obtained from 2 week old Wistar rat pups and 1 day old piglets as described (Am J Physiol 288:R897–902, 2005). Experiments were done on confluent CMVECs within 4–5 days after isolation. Both in rat and piglet CMVCs, L‐glut and NMDA (1‐1mM) 1) did not elevate intracellular Ca 2+ levels unlike calcimycin using Fluo‐4 fluorescence; 2) caused no changes in the characteristic cobblestone appearance of cultures; 3) did not affect transendothelial electrical resistance; 4) did not decrease cell viability; and 5) did not augment cell death induced by 8h medium withdrawal or 12h oxygen‐glucose deprivation. In conclusion, CMVECs in vitro are resistant to glutamatergic stimuli and maintain prominent blood brain barrier features even at doses exceeding the physiological range of L‐glut. Our findings are consistent with previous studies in piglets showing little or no effect of NMDA or L‐glut on pial arterioles in vitro (Microvasc Res 70:76–83, 2005) or damage in vivo (Am J Physiol 257:H1200‐3, 1989). Supported by OTKA K68976, K63401 and by NIH HL30260, HL65380, HL77731.