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The Journal of Neuroscience, January 15, 1999, 19(2):716-725
Lipopolysaccharide Injected into the Cerebral Ventricle Evokes
Fever through Induction of Cyclooxygenase-2 in Brain Endothelial
Cells
Chunyu
Cao,
Kiyoshi
Matsumura,
Masashi
Ozaki, and
Yasuyoshi
Watanabe
Department of Neuroscience, Osaka Bioscience Institute, Furuedai
6-2-4, Suita, Osaka 565-0874, Japan
Activation of the arachidonic acid cascade is an essential step for
the development of fever during brain inflammation. We investigated the
brain sites where this activation takes place by use of a rat model of
brain inflammation. Intracerebroventricular administration of
lipopolysaccharide but not of its vehicle evoked fever. The fever was
markedly suppressed when the rats had been pretreated with a
cyclooxygenase-2-specific inhibitor. In situ hybridization and immunohistochemical studies revealed that
cyclooxygenase-2 mRNA and its protein were induced by
lipopolysaccharide in blood vessels near the cerebral ventricles and in
those in the subarachnoidal space. Double immunohistochemical staining
revealed that these cyclooxygenase-2-positive cells were mostly
endothelial cells. The time course of fever and that of
cyclooxygenase-2 induction in the endothelial cells were in parallel.
Cyclooxygenase-2 mRNA in a certain type of telencephalic neurons was
also upregulated by the intracerebroventricular administration, but
this neuronal response occurred both in vehicle-injected rats and in
lipopolysaccharide-injected ones to the same extent. Therefore, the
neuronal response was not essential to the development of fever. These
results suggest that brain endothelial cells play a crucial role in the
development of fever during brain inflammation by activating their
arachidonic acid cascade.
Key words:
brain inflammation; fever; meningitis; cyclooxygenase; prostaglandin; endothelial cells
Copyright © 1999 Society for Neuroscience 0270-6474/99/192716-10$05.00/0
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