Abstract
The blood-brain barrier (BBB), important in maintaining brain homeostasis, has been shown to be disrupted during pathological states such as stroke. Our previous studies using in vitro and in vivo models demonstrated increases in paracellular permeability following hypoxia (H) and post-hypoxic reoxygenation (H/R) which correlated with changes in tight junction protein expression and cellular localization. Recently, it has been shown that endothelial cells of the BBB express claudin-1, -3 and -5 isoforms. Claudins are transmembrane proteins which are integral in maintaining BBB function/integrity. The present studies investigated the modulation of claudin-1,-3 and -5 mRNA in rat brain microvessel endothelial cells following H (1% O2; 24 h) and H/R (95% Room Air, 5% CO2; 2 h). Analysis of mRNA using real time RT-PCR demonstrated a significant increase in both claudin-3 (9.11 ± 0.652 vs. 1.00 ± 0.674) and claudin-5 (7.45 ± 0.704 vs. 1.00 ± 0.982) following H as compared to normoxia (N). Following H/R, mRNA expression of claudin-1 (19.94 ± 0.295 vs. 1.00 ± 1.063), claudin-3 (8.77 ± 0.403 vs. 1.00 ±.674) and claudin-5 (9.13 ± 0.866 vs. 1.00 ± 0.982) were all significantly increased compared to N. There was no effect of H/R on mRNA expression of claudin-1,-3 or -5 compared to H (0.88 ± 0.295 vs. 1.00 ± 1.1315, 0.96 ±.403 vs. 1.00 ± 0.652, 1.23 ± 0.866 vs. 1.00 ± 0.704, respectively). These data suggest that H and H/R alter claudin-1, -3 and -5 and this may contribute to a loss in BBB integrity following H and H/R. Supported by F32 NS049894 (MAF) and RO1 NS39592 (TPD).
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