Circulating bacterial lipopolysaccharide-induced inflammation reduces flow in brain-irrigating arteries independently from cerebrovascular prostaglandin production. (27th March 2017)

• Record Type: Journal Article
• Authors: Villéga, Frédéric; Delpech, Jean-Christophe; Griton, Marion; André, Caroline; Franconi, Jean-Michel; Miraux, Sylvain; Konsman, Jan Pieter
• Is Part Of: Neuroscience. Volume 346(2017)
• Page Start: 160
• Page End: 172
• Publication Date: 2017-03-27
• Subjects: ACA anterior cerebral artery -- ANOVA analysis of variance -- AUC area under the curve -- COX-2 cyclooxygenase-2 -- ET-1 endothelin-1 -- I interval -- iNOS inducible nitric oxide synthase -- iv intravenous -- LPS lipopolysaccharide -- MCA middle cerebral artery -- MCP-1/CCL2 monocyte chemoattractant protein-1 -- mPGES microsomal prostaglandin E synthase -- MRA magnetic resonance angiography -- NF-κB nuclear factor-kappaB -- PBS phosphate-buffered saline -- PCR polymerase chain reaction -- PVH paraventricular nucleus of the hypothalamus -- REST Relative Expression Software Tool -- ROI region of interest -- TNFα tumor necrosis factor-alpha -- TOF time-of-flight -- UV ultraviolet; angiography -- anterior cerebral artery -- cerebral blood flow -- encephalopathy -- prostaglandin -- sepsis; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.01.018
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Intravenous (iv) bacterial lipopolysaccharide (LPS) administration does not alter internal carotid blood flow. Iv LPS injection lowers flow speed in the middle and anterior cerebral, and some of their downstream, arteries. Iv LPS induces cytokine and vasoactive prostaglandin-synthesizing enzyme mRNA expression in the brain. Iv LPS induces cerebrovascular nuclear factor-kappaB in the absence of increased hypothalamic c-Fos expression. But iv LPS-induced cerebrovascular and cyclooxygenase-2 proteins do not occur in arteries. Abstract: Brain dysfunction is a frequent complication of the systemic inflammatory response to bacterial infection or sepsis. In the present work, the effects of intravenous bacterial lipopolysaccharide (LPS) administration on cerebral arterial blood flow were assessed with time-of-flight (TOF)-based magnetic resonance angiography (MRA) in mice. Cerebral expression of the transcription factors nuclear factor-kappaB (NF-κB) and c-Fos and that of enzymes synthesizing vasoactive mediators, such as prostaglandins and nitric oxide, known to be increased under inflammatory conditions, were studied in the same animals. Time-resolved TOF MRA revealed no differences in blood flow in the internal carotids upstream of the circle of Willis, but indicated lower flow in its lateral parts as well as in the middle and anterior cerebral arteries after intravenous LPS injection as compared to saline administration. Although LPS did not increase c-Fos expression in ventral forebrain structures of these animals, it did induce NF-κB in meningeal blood vessels. LPS also increased cerebral expression of cyclooxygenase-2 and prostaglandin E synthase mRNAs, but de novo expression occurred in veins rather than in arteries. In conclusion, our work indicates that LPS-induced systemic inflammation does not necessarily affect filling of the circle of the Willis from the periphery, but that circulating LPS alters outflow from the circle of Willis to the middle and anterior cerebral arteries. These modifications in arterial flow were not related to increased cerebral synthesis of prostaglandins, but may instead be the consequence of the action of circulating prostaglandins and other vasoactive mediators on brain-irrigating arteries during systemic inflammation.