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      Proteomic changes in traumatic brain injury: experimental approaches

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          Abstract

          Purpose of review

          The underlying mechanisms responsible for chronic and progressive neurological damage after traumatic brain injury (TBI) are poorly understood, and therefore, current treatment options are limited. Proteomics is an emerging methodology to study changes to the TBI proteome in both patients and experimental models.

          Recent findings

          Although experimentally complex, mass spectrometry-based proteomics approaches are converging on a set of common methods. However, these methods are being applied to an increasingly diverse range of experimental models and types of injury.

          Summary

          In this review, our aim is to briefly describe experimental TBI models and the underlying methods common to most proteomic approaches. We will then review a series of articles that have recently appeared in which these approaches have been applied to important TBI questions. We will summarize several recent experimental studies, and suggest how the results of these emerging studies might impact future research as well as patient treatment.

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          Development of a stretch‐induced neurotrauma model for medium‐throughput screening in vitro: identification of rifampicin as a neuroprotectant

          Background and Purpose We hypothesized that an in vitro , stretch‐based model of neural injury may be useful to identify compounds that decrease the cellular damage in neurotrauma. Experimental Approach We screened three neural cell lines (B35, RN33B and SH‐SY5Y) subjected to two differentiation methods and selected all‐trans‐retinoic acid‐differentiated B35 rat neuroblastoma cells subjected to rapid stretch injury, coupled with a subthreshold concentration of H 2 O 2 , for the screen. The model induced marked alterations in gene expression and proteomic signature of the cells and culminated in delayed cell death (LDH release) and mitochondrial dysfunction [reduced 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) conversion]. Follow‐up studies utilized human stem cell‐derived neurons subjected to rapid stretch injury. Key Results From screening of a composite library of 3500 drugs, five drugs (when applied in a post‐treatment regimen relative to stretch injury) improved both LDH and MTT responses. The effects of rifampicin were investigated in further detail. Rifampicin reduced cell necrosis and apoptosis and improved cellular bioenergetics. In a second model (stretch injury in human stem cell‐derived neurons), rifampicin pretreatment attenuated LDH release, protected against the loss of neurite length and maintained neuron‐specific class III β‐tubulin immunoreactivity. Conclusions and Implications We conclude that the current model is suitable for medium‐throughput screening to identify compounds with neuroprotective potential. Rifampicin, when applied either in pre‐ or post‐treatment, improves the viability of neurons subjected to stretch injury and protects against neurite loss. Rifampicin may be a candidate for repurposing for the therapy of traumatic brain injury. Linked Articles This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
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            Author and article information

            Journal
            Curr Opin Neurol
            Curr. Opin. Neurol
            CONEU
            Current Opinion in Neurology
            Lippincott Williams & Wilkins
            1350-7540
            1473-6551
            December 2018
            24 October 2018
            : 31
            : 6
            : 709-717
            Affiliations
            [a ]MD/PhD Combined Degree Program and The Neuroscience Graduate Program
            [b ]Department of Cell Biology, Neuroscience and Anatomy
            [c ]Department of Pharmacology and Toxicology
            [d ]Department of Anesthesiology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA
            Author notes
            Correspondence to James L. Sowers, BA, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0617, USA. E-mail: jlsowers@ 123456utmb.edu
            Article
            WCO310608
            10.1097/WCO.0000000000000613
            6221404
            30358641
            a69912ba-5b1d-4607-8ef5-dd35e4e3a994
            Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc.

            This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

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            Categories
            TRAUMA AND REHABILITATION: Edited by Rajiv R. Ratan and Nicholas D. Schiff
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            biochemical pathway identification,biomarkers,experimental traumatic brain injury models,neurodegeneration,proteomics

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