Cao C, Matsumura K, Ozaki M, Watanabe Y
Department of Neuroscience, Osaka Bioscience Institute, Furuedai 6-2-4, Suita, Osaka 565-0874, Japan.
J Neurosci. 1999 Jan 15;19(2):716-25. doi: 10.1523/JNEUROSCI.19-02-00716.1999.
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.
花生四烯酸级联反应的激活是脑部炎症发热过程中的一个关键步骤。我们通过使用脑部炎症大鼠模型，研究了该激活发生的脑区。脑室内注射脂多糖可引起发热，而注射其溶剂则不会。当大鼠预先用环氧化酶-2特异性抑制剂处理后，发热明显受到抑制。原位杂交和免疫组织化学研究表明，环氧化酶-2 mRNA及其蛋白在脑室附近和蛛网膜下腔的血管中被脂多糖诱导。双重免疫组织化学染色显示，这些环氧化酶-2阳性细胞大多为内皮细胞。发热的时间进程与内皮细胞中环氧化酶-2诱导的时间进程是平行的。脑室内注射也可使某类端脑神经元中的环氧化酶-2 mRNA上调，但这种神经元反应在注射溶剂的大鼠和注射脂多糖的大鼠中程度相同。因此，神经元反应对发热的发生并非必不可少。这些结果表明，脑内皮细胞通过激活其花生四烯酸级联反应，在脑部炎症发热过程中发挥关键作用。
