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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhibitors concurrently with the antibiotic.
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PMID:Nonsteroidal anti-inflammatory agents in the therapy for experimental pneumococcal meningitis. 347 Mar 94

Inflammatory processes occur in the central nervous system (CNS) through mechanisms that differ from other inflammation, and with distinct cellular effects. Neuronal injury in bacterial meningitis is not a monocausal event, but is mediated by several factors. One is possible direct toxicity of bacterial compounds. Lipoteichoic acid (LTA) is a cell wall component unique to Gram-positive bacteria. In a previous report, LTA could interact with CD14 to induce NF-kappaB activation, which is involved in transcriptional regulation of adhesion molecules, enzymes and cytokines. Although there are many aspects to neuroinflammation, the pathways involving the cyclooxygenase (COX)-2 and subsequent generation of prostaglandin clearly play a role. LTA has been shown to stimulate inflammatory responses in a number of in vivo and in vitro experimental models. However, little was known about the molecular mechanisms of LTA implicated in inflammatory responses in neurons. In this study, we characterized the mechanisms underlying signaling transduction in rat cortical neuronal cells challenged by LTA. Here, we first showed that in rat cortical neuronal cells, LTA might activate protein tyrosine kinase (PTK), phosphatidylcholine-specific phospholipase C (PC-PLC), and phosphatidylinositol-specific phospholipase C (PI-PLC) to induce protein kinase Cepsilon activation, which in turn induces extracellular signal-regulated kinase (ERK) activation, finally inducing PGE(2) release and COX-2 synthesis.
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PMID:Lipoteichoic acid induces prostaglandin E(2) release and cyclooxygenase-2 synthesis in rat cortical neuronal cells: involvement of PKCepsilon and ERK activation. 1646 74

Increased permeability of the blood-brain barrier (BBB) is important in neurological disorders. Neuroinflammation is associated with increased BBB breakdown and brain injury. Tumor necrosis factor (TNF)-alpha is involved in BBB injury and edema formation through a mechanism involving matrix metalloproteinase (MMP) up-regulation. There is emerging evidence indicating that cyclooxygenase (COX) inhibition limits BBB disruption following ischemic stroke and bacterial meningitis, but the mechanisms involved are not known. We used intracerebral injection of TNF-alpha to study the effect of COX inhibition on TNF-alpha-induced BBB breakdown, MMP expression/activity, and oxidative stress. BBB disruption was evaluated by the uptake of (14)C-sucrose into the brain and by magnetic resonance imaging utilizing gadolinium-diethylenetriaminepentaacetic acid as a paramagnetic contrast agent. Using selective inhibitors of each COX isoform, we found that COX-1 activity is more important than COX-2 in BBB opening. TNF-alpha induced a significant up-regulation of gelatinase B (MMP-9), stromelysin-1 (MMP-3), and COX-2. In addition, TNF-alpha significantly depleted glutathione as compared with saline. Indomethacin (10 mg/kg i.p.), an inhibitor of COX-1 and COX-2, reduced BBB damage at 24 h. Indomethacin significantly attenuated MMP-9 and MMP-3 expression and activation and prevented the loss of endogenous radical scavenging capacity following intracerebral injection of TNF-alpha. Our results show for the first time that BBB disruption during neuroinflammation can be significantly reduced by administration of COX inhibitors. Modulation of COX in brain injury by COX inhibitors or agents modulating prostaglandin E(2) formation/signaling may be useful in clinical settings associated with BBB disruption.
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PMID:Cyclooxygenase inhibition limits blood-brain barrier disruption following intracerebral injection of tumor necrosis factor-alpha in the rat. 1770 56