[Brain injury induced by continuous infusion of endotoxin in rats--protective effects of methylprednisolone on intracerebral blood vessels].
Hemorrhagic intracerebral lesions, analogous to multiple punctate hemorrhagic necrosis seen in the brain of human disseminated intravascular coagulation (DIC), can be induced in rats by continuous intravenous infusion of E. coli endotoxin lipopolysaccharide (ET) at 88.5 micrograms/hour. The occurrence of cerebral lesions increases with time of ET infusion initially, but levels off after 120 hours of the continuous administration. To investigate protective effects of methylprednisolone (MP) against intracerebral vascular injury, 122 male rats were divided into the basic endotoxemic rats without MP medication (Group 1), and MP medication of 0.2mg/kg body weight, 1.0mg/kg, 2.0mg/kg and 20.0mg/kg immediately before induction of endotoxemia (Groups 2-5), one dose of 20.0mg/kg MP at 48 hours and 2 doses at 48 and 72 hours after induction of endotoxemia (Groups 6-7), and 3 doses each of 2.0mg/kg, 20.0mg/kg and 100.0mg/kg MP for 3 days immediately before and at 24 and 48 hours after induction of endotoxemia (Groups 8-10). All surviving rats were autopsied after 120 hours of ET infusion and histologic sections were made. Multiple hemorrhagic intracerebral lesions developed in 83% (10/12) of Group 1 rats, whereas the frequency of brain lesions in Groups 4, 5, 8, 9 and 10 was significantly lower than that in Group 1 (p < 0.05). Electron microscopically, the frontal lobe cortex of Group 1 after 120 hours of ET infusion showed subendothelial dilatation containing macrophages, and perivascular accumulation of erythrocytes (diapedesis). In contrast, the frontal lobe cortex of Group 5 revealed no appreciable electron microscopic changes of intracerebral blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Tamada
F
F
Department of Pathology, National Defense Medical College, Saitama, Japan.
D000818:Animals; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004731:Endotoxins / Q000097:blood / Q000633:toxicity*; D007262:Infusions, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats
D004731:Endotoxins; D008775:Methylprednisolone