Methylprednisolone reduces the bulk flow of water across an in vitro blood-brain barrier.
Cerebral water content is a variable quantity subject to the influence of hemodynamic and biochemical factors. Corticosteroids are frequently used in the therapy of cerebral edema, although their mechanisms of action in promoting the resolution of this state of pathologically increased water content remains unclear. To investigate this, a modified Ussing chamber was designed. The bulk flow of media (mainly composed of water) across a monolayer of cultured mouse cerebral endothelia was measured as a control. The same membranes were then exposed to either micromolar concentrations of hydrocortisone or methylprednisolone. The hydraulic conductivity (Lp) of each membrane before and after exposure to the corticosteroids was calculated as a reflection of membrane tightness. Methyl-prednisolone decreased the Lp of the membrane (i.e. tightened) by 36.1% compared to control. Hydrocortisone actually increased Lp (i.e. loosened the membrane) but not to a significant extent. The decrease in the bulk flow caused by methylprednisolone in vitro suggests that the mechanism of the clinically observed decrease in cerebral edema after corticosteroid administration may be due to the reduction of bulk flow across the blood-brain barrier.
Olson
J J
JJ
Division of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City 52242.
Poor
M M
MM
Beck
D W
DW
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001834:Body Water / Q000378:metabolism; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D006854:Hydrocortisone / Q000378:metabolism; D007700:Kinetics; D008775:Methylprednisolone / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning
D006854:Hydrocortisone; D008775:Methylprednisolone