Plasma metabolomics profiles in rats with acute traumatic brain injury

PLOS ONE, Dec 2019

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. We validated the utility of plasma metabolomics analysis in the clinical diagnosis of acute TBI in a rat model of controlled cortical impact (CCI) using gas chromatography/mass spectrometry (GC/MS). Thirty Sprague-Dawley rats were randomly divided into two groups of 15 rats each: the CCI group and sham group. Blood samples were obtained from the rats within the first 24 h after TBI injury. GC/MS measurements were performed to evaluate the profile of acute TBI-induced metabolic changes, resulting in the identification of 45 metabolites in plasma. Principal component analysis, partial least squares-discriminant analysis, orthogonal partial least square discriminant analysis using hierarchical clustering and univariate/multivariate analyses revealed clear differences in the plasma metabolome between the acute CCI group and the sham group. CCI induced distinctive changes in metabolites including linoleic acid metabolism, amino acid metabolism, galactose metabolism, and arachidonic acid metabolism. Specifically, the acute CCI group exhibited significant alterations in proline, phosphoric acid, β-hydroxybutyric acid, galactose, creatinine, L-valine, linoleic acid and arachidonic acid. A receiver operating characteristic curve analysis showed that the above 8 metabolites in plasma could be used as the potential biomarkers for the diagnosis of acute TBI. Furthermore, this study is the first time to identify the galactose as a biomarker candidate for acute TBI. This comprehensive metabolic analysis complements target screening for potential diagnostic biomarkers of acute TBI and enhances predictive value for the therapeutic intervention of acute TBI.

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Plasma metabolomics profiles in rats with acute traumatic brain injury

August Plasma metabolomics profiles in rats with acute traumatic brain injury Fei Zheng 0 1 Zi-An Xia 1 Yi-Fu Zeng 0 1 Jie-Kun Luo 1 Peng Sun 1 Han-Jin Cui 1 Yang Wang 1 Tao Tang 1 Yan-Tao Zhou 0 1 0 College of Electrical and Information Engineering, Hunan University , Changsha , China , 2 Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University , Changsha , China , 3 College of Pharmacy, Shandong University of Traditional Chinese Medicine , Jinan , China 1 Editor: Firas H Kobeissy, University of Florida , UNITED STATES Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. We validated the utility of plasma metabolomics analysis in the clinical diagnosis of acute TBI in a rat model of controlled cortical impact (CCI) using gas chromatography/mass spectrometry (GC/MS). Thirty Sprague-Dawley rats were randomly divided into two groups of 15 rats each: the CCI group and sham group. Blood samples were obtained from the rats within the first 24 h after TBI injury. GC/MS measurements were performed to evaluate the profile of acute TBI-induced metabolic changes, resulting in the identification of 45 metabolites in plasma. Principal component analysis, partial least squares-discriminant analysis, orthogonal partial least square discriminant analysis using hierarchical clustering and univariate/ multivariate analyses revealed clear differences in the plasma metabolome between the acute CCI group and the sham group. CCI induced distinctive changes in metabolites including linoleic acid metabolism, amino acid metabolism, galactose metabolism, and arachidonic acid metabolism. Specifically, the acute CCI group exhibited significant alterations in proline, phosphoric acid, β-hydroxybutyric acid, galactose, creatinine, L-valine, linoleic acid and arachidonic acid. A receiver operating characteristic curve analysis showed that the above 8 metabolites in plasma could be used as the potential biomarkers for the diagnosis of acute TBI. Furthermore, this study is the first time to identify the galactose as a biomarker candidate for acute TBI. This comprehensive metabolic analysis complements target screening for potential diagnostic biomarkers of acute TBI and enhances predictive value for the therapeutic intervention of acute TBI. - Data Availability Statement: All relevant data are within the paper and its Supporting Information file. Competing interests: The authors have declared that no competing interests exist. Introduction Traumatic brain injury (TBI) is the result of direct trauma from an external mechanical force on the brain. TBI is a major cause of mortality and disability worldwide, especially in individuals under the age of 45 years [ 1 ]. According to the Centers for Disease Control and Prevention (CDCP), an estimated 1.7 million people in the United States suffer TBI annually [ 2 ]. Approximately 5.3 million U.S. residents are living with TBI-induced disabilities, including psychological and long-term cognitive impairments [ 3 ]. Increasing evidence indicates that appropriate and timely diagnosis with subsequent intervention in acute TBI can minimize insults and decrease neurological disability [4±6]. Therefore, there is a window of golden opportunity in optimizing the prognosis of TBI patients. If the molecular mechanism of acute TBI could be deciphered, effective treatments might be developed, and then associated mortality might be reduced. The molecular events including neuroinflammation [ 7 ], tauopathy [ 8 ], blood-brain barrier (BBB) dysfunction [ 9 ] and brain edema [ 10 ] characterize the progression of acute TBI. However, the knowledge of the molecular mechanisms of acute TBI is relatively limited due to the multifactorial nature of the acute TBI pathology. Numerus potential molecular mechanisms remain unknown, hindering a comprehensive and effective elucidation of acute TBI. Because of the complicated TBI, single biomarker could not reflect the full spectrum of the response of brain tissue to TBI [ 11 ]. Hence, to reveal a global view of the complex and multiple molecular mechanisms of acute TBI is urgently needed [ 12 ]. Extensive efforts have focused on the molecular mechanisms underlying acute TBI to identify optimal intervention and therapeutic strategies. Currently, the clinical diagnosis of acute TBI includes brain edema, alterations in cerebral blood flow and metabolic changes [ 13,14 ]. Among these changes, the measurement of metabolic alterations in the biofluid is important for the clinical diagnosis. Metabolic progress in the body results in the changes in the concentrations of metabolites. The characterization of the release of these specific metabolites during the metabolic changes could clarify the pathophysiology and the potential therapeutic targets. Several metabolic biomarkers of acute TBI have been proposed, including S100 calcium binding p (...truncated)


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Fei Zheng, Zi-An Xia, Yi-Fu Zeng, Jie-Kun Luo, Peng Sun, Han-Jin Cui, Yang Wang, Tao Tang, Yan-Tao Zhou. Plasma metabolomics profiles in rats with acute traumatic brain injury, PLOS ONE, 2017, Volume 12, Issue 8, DOI: 10.1371/journal.pone.0182025