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- W2000616631 abstract "METHYLPREDNISOLONE (MP) IS ONE of the most widely used neuroprotective drugs in neurosurgery. Our knowledge of its pharmacokinetics in the brain and, in particular, whether it can penetrate the blood-brain barrier (BBB) and act in the brain parenchyma is still limited. In this study, we used a vascular brain perfusion technique in guinea pigs, combined with a capillary depletion method, to determine brain uptake and transport of MP at the BBB.3 H-Labeled MP was delivered to the brain by carotid arterial infusions lasting from 1 to 10 minutes; the effects of plasma protein binding, different concentrations of MP, and the glucocorticoid receptor inhibitor, RU486, were examined. The existence of a transport system was inferred from the observation that the volume of distribution of MP in the brain after perfusion exceeded by 2.6 to 6.3 times the plasma volume of the cerebrovascular space marker, sucrose. The rates of unidirectional [3H]MP blood-to-brain transport of 0.5 to 0.7 μl per minute per gram indicated significant but slow transfer. MP available for BBB transport was not restricted to its free plasma fraction but, instead, included the albumin- and globulin-bound fractions. A portion of steroid remained concentrated (sequestered) by the capillary endothelium, and from there, the label was distributed into brain parenchyma. Both MP binding and transport at the BBB exhibited saturable kinetics. RU486 produced an inhibition of MP BBB transport and binding with an affinity that seemed to be 30 to 60% higher than that of the steroid itself. We concluded that MP first binds to the brain capillaries and then crosses the BBB at a low rate, most likely by using a saturable mechanism that may involve a cytoplasmic endothelial glucocorticoid receptor." @default.
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- W2000616631 date "1996-02-01" @default.
- W2000616631 modified "2023-10-18" @default.
- W2000616631 title "Cellular Uptake and Transport of Methylprednisolone at the Blood-Brain Barrier" @default.
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- W2000616631 doi "https://doi.org/10.1097/00006123-199602000-00023" @default.
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