Effect of dexamethasone administered with magnesium sulfate on inflammation-mediated degradation of the blood-brain barrier using an in vitro model.
Patients at risk for preterm delivery are frequently administered both antenatal steroids for fetal maturation and magnesium sulfate for neuroprotection. In this study, we investigate whether steroids coadministered with magnesium sulfate preserve blood-brain barrier integrity in neuroinflammation. Human umbilical vein endothelial cells were grown in astroglial conditioned media in a 2-chamber cell culture apparatus. Treatment with tumor necrosis factor-α (TNF-α) or catalytically active recombinant matrix metalloproteinase 9 (MMP-9) simulated neuroinflammation. Membrane integrity was assessed by zona occludens 1 (ZO-1) immunoreactivity, permeability to fluorescently conjugated dextran, and transendothelial electrical resistance (TEER). The TNF-α and MMP-9 treatment increased the rate of dextran transit, decreased TEER, and decreased ZO-1 immunoreactivity at junctional interfaces. Dexamethasone pretreatment alone or in combination with 0.5 mmol/L magnesium sulfate preserved monolayer integrity after inflammatory insult. Magnesium sulfate alone was not protective. This study supports a possible interaction between steroids and magnesium in neuroprotection.
1Department of Obstetrics and Gynecology, Maternal Fetal Medicine, Madigan Army Medical Center, Tacoma, WA, USA.
Monica A
MA
Lutgendorf
Danielle L
DL
Ippolito
Mariano T
MT
Mesngon
Deborah
D
Tinnemore
Mary Jo
MJ
Dehart
Brad M
BM
Dolinsky
Peter G
PG
Napolitano
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D017097:Electric Impedance; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D008278:Magnesium Sulfate / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
D017077:Culture Media, Conditioned; D005938:Glucocorticoids; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; C569042:TJP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D008278:Magnesium Sulfate; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9
magnesium; matrix metalloproteinase 9; neuroprotection