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      Controlled Cortical Impact and Craniotomy Induce Strikingly Similar Profiles of Inflammatory Gene Expression, but with Distinct Kinetics

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          Abstract

          An immediate consequence of traumatic brain injury (TBI) is the induction of an inflammatory response. Mounting data suggest that inflammation is a major contributor to TBI-induced brain damage. However, much remains unknown regarding the induction and regulation of the inflammatory response to TBI. In this study we compared the TBI-induced inflammatory response to severe parenchymal injury (controlled cortical impact) vs. mild brain injury (craniotomy) over a 21-day period. Our data show that both severe and mild brain injury induce a qualitatively similar inflammatory response, involving highly overlapping sets of effector molecules. However, kinetic analysis revealed that the inflammatory response to mild brain injury is of much shorter duration than the response to severe TBI. Specifically, the inflammatory response to severe brain injury persists for at least 21 days, whereas the response to mild brain injury returns to near baseline values within 10 days post-injury. Our data therefore imply that the development of accurate diagnostic tests of TBI severity that are based on imaging or biomarker analysis of the inflammatory response may require repeated measures over at least a 10-day period, post-injury.

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          Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

          Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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            Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

            A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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              Origin and physiological roles of inflammation.

              Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.
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                Author and article information

                Journal
                Front Neurol
                Front Neurol
                Front. Neur.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                31 October 2012
                2012
                : 3
                : 155
                Affiliations
                [1] 1Department of Microbiology and Immunology, Uniformed Services University Bethesda, MD, USA
                [2] 2Center for Neuroscience and Regenerative Medicine, Uniformed Services University Bethesda, MD, USA
                [3] 3Department of Anatomy, Physiology, and Genetics, Uniformed Services University Bethesda, MD, USA
                Author notes

                Edited by: Frank Tortella, Walter Reed Army Institute of Research, USA

                Reviewed by: William Doster Watson, Uniformed Services University, USA; Joseph Long, Walter Reed Army Institute of Research, USA

                *Correspondence: Brian C. Schaefer, Department of Microbiology and Immunology, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. e-mail: brian.schaefer@ 123456usuhs.edu

                This article was submitted to Frontiers in Neurotrauma, a specialty of Frontiers in Neurology.

                Article
                10.3389/fneur.2012.00155
                3484408
                23118733
                27925b35-acb1-4b7b-a5b6-ba477dbcc132
                Copyright © 2012 Lagraoui, Latoche, Cartwright, Sukumar, Dalgard and Schaefer.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 19 June 2012
                : 09 October 2012
                Page count
                Figures: 6, Tables: 4, Equations: 0, References: 32, Pages: 14, Words: 8704
                Categories
                Neuroscience
                Original Research

                Neurology
                inflammation,traumatic brain injury,response to injury,genomics,diagnostics,mouse models,glia,cytokines

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