Dataset Information

ITRAQ-Based Quantitative Proteomics Reveals the New Evidence Base for Traumatic Brain Injury Treated with Targeted Temperature Management.

ABSTRACT: This study aimed to investigate the effects of targeted temperature management (TTM) modulation on traumatic brain injury (TBI) and the involved mechanisms using quantitative proteomics technology. SH-SY5Y and HT-22 cells were subjected to moderate stretch injury using the cell injury controller (CIC), followed by incubation at TTM (mild hypothermia, 32°C), or normothermia (37°C). The real-time morphological changes, cell cycle phase distribution, death, and cell viability were evaluated. Moderate TBI was produced by the controlled cortical impactor (CCI), and the effects of TTM on the neurological damage, neurodegeneration, cerebrovascular histopathology, and behavioral outcome were determined in vivo. Results showed that TTM treatment prevented TBI-induced neuronal necrosis in the brain, achieved a substantial reduction in neuronal death both in vitro and in vivo, reduced cortical lesion volume and neuronal loss, attenuated cerebrovascular histopathological damage, brain edema, and improved behavioral outcome. Using an iTRAQ proteomics approach, proteins that were significantly associated with TTM in experimental TBI were identified. Importantly, changes in four candidate molecules (plasminogen [PLG], antithrombin III [AT III], fibrinogen gamma chain [FGG], transthyretin [TTR]) were verified using TBI rat brain tissues and TBI human cerebrospinal fluid (CSF) samples. This study is one of the first to investigate the neuroprotective effects of TTM on the proteome of human and experimental models of TBI, providing an overall landscape of the TBI brain proteome and a scientific foundation for further assessment of candidate molecules associated with TTM for the promotion of reparative strategies post-TBI.

SUBMITTER: Cheng SX

PROVIDER: S-EPMC5794703 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

iTRAQ-Based Quantitative Proteomics Reveals the New Evidence Base for Traumatic Brain Injury Treated with Targeted Temperature Management.

Cheng Shi-Xiang SX Xu Zhong-Wei ZW Yi Tai-Long TL Sun Hong-Tao HT Yang Cheng C Yu Ze-Qi ZQ Yang Xiao-Sa XS Jin Xiao-Han XH Tu Yue Y Zhang Sai S

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20180101 1

This study aimed to investigate the effects of targeted temperature management (TTM) modulation on traumatic brain injury (TBI) and the involved mechanisms using quantitative proteomics technology. SH-SY5Y and HT-22 cells were subjected to moderate stretch injury using the cell injury controller (CIC), followed by incubation at TTM (mild hypothermia, 32°C), or normothermia (37°C). The real-time morphological changes, cell cycle phase distribution, death, and cell viability were evaluated. Modera ...[more]

PMID: 29247448

Similar Datasets

Project description:BackgroundLittle is known about the prevalence of altered CAR in anoxic brain injury and the association with patients' outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome.MethodsRetrospective analysis of prospectively collected data.Inclusion criteriaadult cardiac arrest survivors treated by targeted temperature management (TTM).Exclusion criteriatrauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3-5 assessed 3 months after CA defined unfavorable neurological outcome (UO).ResultsWe included 50 patients (Jan 2015-Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10-35] min. HT (core body temperature 33.7 [33.2-34] °C) lasted for 24 [23-28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6-37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11-0.58] vs. 0.58 [0.30-0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43-0.83] vs. 0.31 [- 0.01-0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO.ConclusionsCAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.

Project description:Atropine, a muscarinic antagonist, is known to inhibit myopia progression in several animal models and humans. However, the mode of action is not established yet. In this study, we compared quantitative iTRAQ proteomic analysis in the retinas collected from control and lens-induced myopic (LIM) mouse eyes treated with atropine. The myopic group received a (-15D) spectacle lens over the right eye on postnatal day 10 with or without atropine eye drops starting on postnatal day 24. Axial length was measured by optical low coherence interferometry (OLCI), AC-Master, and refraction was measured by automated infrared photorefractor at postnatal 24, 38, and 52 days. Retinal tissue samples were pooled from six eyes for each group. The experiments were repeated twice, and technical replicates were also performed for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. MetaCore was used to perform protein profiling for pathway analysis. We identified a total of 3882 unique proteins with <1% FDR by analyzing the samples in replicates for two independent experiments. This is the largest number of mouse retina proteome reported to date. Thirty proteins were found to be up-regulated (ratio for myopia/control > global mean ratio + 1 standard deviation), and 28 proteins were down-regulated (ratio for myopia/control < global mean ratio - 1 standard deviation) in myopic eyes as compared with control retinas. Pathway analysis using MetaCore revealed regulation of ?-aminobutyric acid (GABA) levels in the myopic eyes. Detailed analysis of the quantitative proteomics data showed that the levels of GABA transporter 1 (GAT-1) were elevated in myopic retina and significantly reduced after atropine treatment. These results were further validated with immunohistochemistry and Western blot analysis. In conclusion, this study provides a comprehensive quantitative proteomic analysis of atropine-treated mouse retina and suggests the involvement of GABAergic signaling in the antimyopic effects of atropine in mouse eyes. The GABAergic transmission in the neural retina plays a pivotal role in the maintenance of axial eye growth in mammals.

Dataset Information

ITRAQ-Based Quantitative Proteomics Reveals the New Evidence Base for Traumatic Brain Injury Treated with Targeted Temperature Management.

Publications

iTRAQ-Based Quantitative Proteomics Reveals the New Evidence Base for Traumatic Brain Injury Treated with Targeted Temperature Management.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets