MURASE Masahiko Gifu University, School of Medicine, Research Associate, 医学部, 助手 (80221620)
OHNISHI Hiroo Gifu University, School of Medicine, Assistant Professor, 医学部・附属病院, 講師 (40176954)
|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1993 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1992 : ¥900,000 (Direct Cost : ¥900,000)
Experimental studies were conducted to investigate the mechanisms and treatments of brain edema in acute hepatic failure(AHF) model, with special reference to functional disorders of the blood-brain barrier(BBB) in hepatic encephalopathy. The experimental AHF rat model was produced by intraperitoneal administration of D-galactosamine hydrochloride(GalN) and lipopolysaccaride.
1) Brain water contents were gradually increased according to deterioration of hepatic encephalopathy. In addition, AHF rat model showed gradual increase of permeability of inulin(approximately 5,200 daltons) through the BBB by Oldendorf's method.
2) Brain water contents in AHF rat model significantly decreased, when mannitol was administered intravenously at 8, 16, and 24 hours after treatment of GalN and LPS.However, this effect of mannitol weakened in parallel with progression of hepatic encephalopathy, due to the elevation of permeability through the BBB and brain concentration of mannitol. Therefore, mannitol treatment for brain edema should be started in earlier stage of hepatic encephalopathy.
3) Prostaglandin I_2(PGI_2) derivative administration significantly decreased brain water contents and permeability of inulin through the BBB, when compared with prostaglandin E_1(PG E_1) or saline injected AHF rat model. PGI_2 derivative was considered to show the effect for brain edema in AHF, due to inhibition of BBB permeability and preservation of its integrity.
Mannitol treatment together with PGI_2 derivative significantly inhibited the progression of brain edema in AHF rat model, when compared with mannitol or PGI_2 derivative alone, respectively. PGI_2 derivative inhibited the permeability of mannitol through BBB, and decreased mannitol concentration in brain. Therefore, administration of mannitol with PGI_2 derivative was considered to be more effective to brain edema in AHF.