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00925njm 22002777a 4500 dc García Bueno, Borja author Serrats, Jordi author Sawchenko, Paul E. author 2009-09-04 Systemic injection of lipopolysaccharide (LPS) is a widely used model of immune/inflammatory challenge, which can invoke a host of CNS responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis. Inducible vascular prostaglandin E2 (PGE2) synthesis by endothelial (ECs) and/or perivascular cells (PVCs) (a macrophage-derived vascular cell type) is implicated in the engagement of HPA and other CNS responses, by virtue of their capacity to express cyclooxygenase-2 (COX-2) and microsomal PGE 2 synthase-1. Evidence from genetic and pharmacologic studies also supports a role for the constitutively expressed COX-1 in inflammation-induced activation of the HPA axis, although histochemical evidence to support relevant localization(s) and regulation of COX-1 expression is lacking. The present experiments fill this void in showing that COX-1 immunoreactivity (IR) and mRNA are detectable in identified PVCs and parenchymal microglia under basal conditions and is robustly expressed in these and ECs 1-3 h after intravenous injection of LPS (2 μg/kg). Confocal and electron microscopic analyses indicate distinct cellular/subcellular localizations of COX-1-IR in the three cell types. Interestingly, COX-1 expression is enhanced in ECs of brain PVC-depleted rats, supporting an anti-inflammatory role of the latter cell type. Functional involvement of COX-1 is indicated by the observation that central, but not systemic, pretreatment with the selective COX-1 inhibitor SC-560 attenuated the early phase of LPS-induced increases in adrenocorticotropin and corticosterone secretion. These findings support an involvement of COX-1 in bidirectional interplay between ECs and PVCs in initiating vascular PGE 2 and downstream HPA response to proinflammatory challenges. García-Bueno B, Serrats J, Sawchenko PE. Cerebrovascular Cyclooxygenase-1 Expression, Regulation, and Role in Hypothalamic-Pituitary-Adrenal Axis Activation by Inflammatory Stimuli. J Neurosci 2009;29:12970–81. https://doi.org/10.1523/JNEUROSCI.2373-09.2009 10.1523/JNEUROSCI.2373-09.2009. https://hdl.handle.net/20.500.14352/134328 https://doi.org/10.1523/JNEUROSCI.2373-09.2009 https://www.jneurosci.org/content/29/41/12970 Cerebrovascular Cyclooxygenase-1 Expression, Regulation, and Role in Hypothalamic-Pituitary-Adrenal Axis Activation by Inflammatory Stimuli