Quan N, Whiteside M, Herkenham M
Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, MD 20892-4070, USA.
Brain Res. 1998 Aug 17;802(1-2):189-97. doi: 10.1016/s0006-8993(98)00402-8.
Inducible cyclooxygenase 2 (COX 2) converts arachidonic acid to prostaglandins, which are thought to mediate various peripheral lipopolysaccharide (LPS)-induced central effects, including generation of fever and activation of the hypothalamic-pituitary-adrenal axis. To localize prostaglandin production in the brain following peripheral LPS administration, COX 2 mRNA expression was examined by in situ hybridization histochemistry in rats injected intraperitoneally (i.p.) or intravenously (i.v.) with various doses of LPS or saline. Constitutive expression of COX 2 mRNA was found in neurons of cortex, hippocampus, and amygdala, but not in cells of the blood vessels. COX 2 mRNA levels were not altered in saline-injected animals as compared to non-injected controls. In LPS-injected animals, no consistent changes of neuronal COX 2 mRNA expression were observed. COX 2 mRNA expression appeared ex novo at 0.5-h post-injection in cells closely associated with blood vessels, however, ex novo labeling of the number of labeled cells increased to a peak at 2 h and subsided gradually to basal levels by 24 h. Initially, labeling was observed in cells comprising major surface-lying blood vessels and meninges. Later, vascular and perivascular cells associated with smaller penetrating blood vessels were labeled. This pattern of COX 2 mRNA induction is independent of the route and dose of the LPS injection. The induced COX 2 mRNA producing cells are identified as endothelial and leptomeningeal cells. Changes in COX 2 mRNA expression were not observed in circumventricular organs. These results suggest that peripheral LPS induces a rapid increase in COX 2 production throughout the vasculatures of the brain, which could affect the neuronal activity of widespread brain regions by elevating the levels of prostaglandins.
诱导型环氧化酶2（COX 2）可将花生四烯酸转化为前列腺素，人们认为前列腺素介导多种外周脂多糖（LPS）诱导的中枢效应，包括发热的产生以及下丘脑 - 垂体 - 肾上腺轴的激活。为了定位外周给予LPS后大脑中前列腺素的产生部位，通过原位杂交组织化学法检测了腹腔内（i.p.）或静脉内（i.v.）注射不同剂量LPS或生理盐水的大鼠脑中COX 2 mRNA的表达。在皮质、海马和杏仁核的神经元中发现了COX 2 mRNA的组成性表达，但在血管细胞中未发现。与未注射的对照组相比，注射生理盐水的动物中COX 2 mRNA水平没有改变。在注射LPS的动物中，未观察到神经元COX 2 mRNA表达的一致变化。然而，在注射后0.5小时，与血管紧密相关的细胞中出现了COX 2 mRNA的从头表达，标记细胞数量的从头标记在2小时增加到峰值，并在24小时逐渐降至基础水平。最初，在包括主要位于表面的血管和脑膜的细胞中观察到标记。后来，与较小的穿透性血管相关的血管和血管周围细胞被标记。这种COX 2 mRNA诱导模式与LPS注射的途径和剂量无关。诱导产生COX 2 mRNA的细胞被鉴定为内皮细胞和软脑膜细胞。在室周器官中未观察到COX 2 mRNA表达的变化。这些结果表明，外周LPS诱导整个脑血管系统中COX 2产生迅速增加，这可能通过提高前列腺素水平影响广泛脑区的神经元活动。
