A novel permissive role for glucocorticoids in induction of febrile and behavioral signs of experimental herpes simplex virus encephalitis

被引:28
作者
Ben-Hur, T
Cialic, R
Itzik, A
Barak, O
Yirmiya, R
Weidenfeld, J
机构
[1] Hebrew Univ Jerusalem, Hadassah Univ Hosp, Dept Neurol, IL-91120 Jerusalem, Israel
[2] Hebrew Univ Jerusalem, Dept Psychol, IL-91120 Jerusalem, Israel
关键词
adrenocortical axis; viral encephalitis; fever; motor activity; interleukin-1; prostaglandin E2;
D O I
10.1016/S0306-4522(01)00404-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Herpes simplex virus type I (HSV-1) encephalitis may present with fever and behavioral changes, to the extent of a psychotic state and psychomotor agitation. We developed a clinically relevant experimental model of HSV-1 encephalitis and investigated host brain responses associated with its clinical signs and whether these responses depend on the presence of circulating glucocorticoids. Intracerebral inoculation of HSV-1 in rats induced fever, motor hyperactivity and aggressive behavior. In adrenalectomized rats HSV-1 failed to induce these signs, although mortality rate was identical to sham-operated rats. Hypophysectomy or blocking glucocorticoid receptors also prevented HSV-1-induced fever. Dexamethasone replacement therapy to adrenalectomized rats restored the HSV-1-induced fever and behavioral abnormalities. HSV-1 inoculation produced hyperproduction of prostaglandin E-2 by brain slices. This effect was abolished in adrenalectomized rats and was restored by dexamethasone treatment. In intact rats HSV-1 induced brain interleukin-1 beta (IL-1 beta) gene expression. Adrenalectomy alone caused brain IL-1 beta expression, which did not increase after HSV-1 infection. Similarly, HSV-1 induced IL-1 beta expression in astrocyte cultures. Removal of cortisol from the culture medium caused basal IL-1 beta mRNA expression which was not increased by infection. In conclusion, fever, motor hyperactivity and aggressive behavior during experimental HSV-1 encephalitis are dependent on brain responses, including prostaglandin E-2 and IL-1 beta synthesis. Circulating glucocorticoids play an essential permissive role in the induction of these host brain responses. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:119 / 127
页数:9
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