ABSTRACT
The pathology of sepsis-associated encephalopathy (SAE) is related to astrocyte-inflammation associated with aquaporin-4 (AQP4). The aim here is to investigate the effects of AQP4 associated with SAE and reveal its underlying mechanism causing cognitive impairment. The in vivo experimental results reveal that AQP4 in peripheral blood of patients with SAE is up-regulated, also the cortical and hippocampal tissue of cecal ligation and perforation (CLP) mouse brain has significant rise in AQP4. Furthermore, the data suggest that AQP4 deletion could attenuate learning and memory impairment, attributing to activation of astrocytic autophagy, inactivation of astrocyte and downregulate the expression of proinflammatory cytokines induced by CLP or lipopolysaccharide (LPS). Furthermore, the activation effect of AQP4 knockout on CLP or LPS-induced PPAR-γ inhibiting in astrocyte is related to intracellular Ca2+ level and sodium channel activity. Learning and memory impairment in SAE mouse model are attenuated by AQP4 knockout through activating autophagy, inhibiting neuroinflammation leading to neuroprotection via down-regulation of Nav 1.6 channels in the astrocytes. This results in the reduction of Ca2+ accumulation in the cell cytosol furthermore activating the inhibition of PPAR-γ signal transduction pathway in astrocytes.
Subject(s)
Cognitive Dysfunction , Sepsis-Associated Encephalopathy , Animals , Mice , Astrocytes/metabolism , Autophagy , Cognitive Dysfunction/etiology , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , Peroxisome Proliferator-Activated Receptors/metabolism , Peroxisome Proliferator-Activated Receptors/pharmacology , Sepsis-Associated Encephalopathy/metabolism , HumansABSTRACT
BACKGROUND: Neutrophil-lymphocyte ratio (NLR) is one of the markers of systemic inflammation. Recent studies have associated NLR with diagnosis of preeclampsia (PE). However, due to small sample sizes and different research design, the diagnostic value of NLR in PE patients is not well understood. In this study, we evaluate the potential diagnostic value of NLR in PE. METHODS: We searched PubMed, Embase, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI) databases, Wanfang data, VIP database and China Biomedical Literature Database systematically for relevant literatures up to May 20, 2018. All analyses were conducted using Meta-DiSc1.4 and Stata 12.0 software. Sensitivity, specificity and other measures of accuracy of NLR for the diagnosis of PE were pooled. Meta-regression was performed to identify the sources of heterogeneity. RESULTS: This meta-analysis included a total of 7 studies. The pooled sensitivity and specificity were 0.74 (95% CI 0.71-0.76) and 0.64 (95%CI 0.61-0.68), positive likelihood ratio, 2.62 (95%CI1.79-3.84); negative likelihood ratio, 0.34 (95%CI 0.24-0.48); diagnostic odds ratio, 8.44 (95%CI 4-17.78), and area under the curve was 0.82. Meta regression showed that sample size was the main source of heterogeneity. Deeks funnel plot showed that there was no statistical significance for the evaluation of publication bias (Pâ=â.16). CONCLUSION: Current evidence suggests that the diagnostic accuracy of NLR has unsatisfactory specificity but acceptable sensitivity for diagnosis of PE. Further large-scale prospective studies are required to validate the potential applicability of using NLR alone or in combination other markers as PE diagnostic biomarker and explore potential factors that may influence the accuracy of NLR for PE diagnosis.
