Dataset Information

Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in rats with acute traumatic brain injury.

ABSTRACT: Xuefu Zhuyu Decoction (XFZY), an important traditional Chinese herbal formula, has been reported effective on traumatic brain injury (TBI) in rats. However, its cerebral protection mechanism has not been clarified at the metabolic level. This work aims to explore the global metabolic characteristics of XFZY in rats during the acute phase of TBI on days 1 and 3. A plasma metabolomics method based on gas chromatography-mass spectrometry coupled with univariate analysis and multivariate statistical analysis was performed in three groups (Sham, Vehicle, XFZY). Then, a pathway analysis using MetaboAnalyst 3.0 was performed to illustrate the pathways of therapeutic action of XFZY in TBI. XFZY treatment attenuates neurological dysfunction and cortical lesion volume post-injury on day 3, and reverses the plasma metabolite abnormalities (glutamic acid, lactic acid, 3-hydroxybutyric acid, and ribitol, etc.). These differential metabolites are mainly involved in D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and inositol phosphate metabolism. Our study reveals potential biomarkers and metabolic networks of acute TBI and neuroprotection effects of XFZY, and shows this metabolomics approach with MetaboAnalyst would be a feasible way to systematically study therapeutic effects of XFZY on TBI.

SUBMITTER: Feng D

PROVIDER: S-EPMC5706905 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in rats with acute traumatic brain injury.

Feng Dandan D Xia Zian Z Zhou Jing J Lu Hongmei H Zhang Chunhu C Fan Rong R Xiong Xingui X Cui Hanjin H Gan Pingping P Huang Wei W Peng Weijun W He Feng F Wang Zhiming Z Wang Yang Y Tang Tao T

Oncotarget 20171016 55

Xuefu Zhuyu Decoction (XFZY), an important traditional Chinese herbal formula, has been reported effective on traumatic brain injury (TBI) in rats. However, its cerebral protection mechanism has not been clarified at the metabolic level. This work aims to explore the global metabolic characteristics of XFZY in rats during the acute phase of TBI on days 1 and 3. A plasma metabolomics method based on gas chromatography-mass spectrometry coupled with univariate analysis and multivariate statistical ...[more]

PMID: 29212259

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Project description:Severe traumatic brain injury (TBI) induces seizures or status epilepticus (SE) in 20-30% of patients during the acute phase. We hypothesized that severe TBI induced with lateral fluid-percussion injury (FPI) triggers post-impact SE. Adult Sprague-Dawley male rats were anesthetized with isoflurane and randomized into the sham-operated experimental control or lateral FPI-induced severe TBI groups. Electrodes were implanted right after impact or sham-operation, then video-electroencephalogram (EEG) monitoring was started. In addition, video-EEG was recorded from naïve rats. During the first 72 h post-TBI, injured rats had seizures that were intermingled with other epileptiform EEG patterns typical to non-convulsive SE, including occipital intermittent rhythmic delta activity, lateralized or generalized periodic discharges, spike-and-wave complexes, poly-spikes, poly-spike-and-wave complexes, generalized continuous spiking, burst suppression, or suppression. Almost all (98%) of the electrographic seizures were recorded during 0-72 h post-TBI (23.2 ± 17.4 seizures/rat). Mean latency from the impact to the first electrographic seizure was 18.4 ± 15.1 h. Mean seizure duration was 86 ± 57 sec. Analysis of high-resolution videos indicated that only 41% of electrographic seizures associated with behavioral abnormalities, which were typically subtle (Racine scale 1-2). Fifty-nine percent of electrographic seizures did not show any behavioral manifestations. In most of the rats, epileptiform EEG patterns began to decay spontaneously on Days 5-6 after TBI. Interestingly, also a few sham-operated and naïve rats had post-operation seizures, which were not associated with EEG background patterns typical to non-convulsive SE seen in TBI rats. To summarize, our data show that lateral FPI-induced TBI results in non-convulsive SE with subtle behavioral manifestations; this explains why it has remained undiagnosed until now. The lateral FPI model provides a novel platform for assessing the mechanisms of acute symptomatic non-convulsive SE and for testing treatments to prevent post-injury SE in a clinically relevant context.

Project description:BACKGROUND:Traumatic brain injury (TBI) has increased in rank among traumatic injuries worldwide. Traumatic brain injury is a serious obstacle given that its complex pathology represents a long-term process. Recently, systems biology strategies such as metabolomics to investigate the multifactorial nature of TBI have facilitated attempts to find biomarkers and probe molecular pathways for its diagnosis and therapy. METHODS:This study included a group of 20 rats with controlled cortical impact and a group of 20 sham rats. We utilized mNSS tests to investigate neurological metabolic impairments on day 1 and day 3. Furthermore, we applied metabolomics and bioinformatics to determine the metabolic perturbation caused by TBI during the acute period in the hippocampus tissue of controlled cortical impact (CCI) rats. Notably, TBI-protein-metabolite subnetworks identified from a database were assessed for associations between metabolites and TBI by the dysregulation of related enzymes and transporters. RESULTS:Our results identified 7 and 8 biomarkers on day 1 and day 3, respectively. Additionally, related pathway disorders showed effects on arginine and proline metabolism as well as taurine and hypotaurine metabolism on day 3 in acute TBI. Furthermore, according to metabolite-protein database searches, 25 metabolite-protein pairs were established as causally associated with TBI. Further, bioinformation indicated that these TBI-associated proteins mainly take part in 5'-nucleotidase activity and carboxylic acid transmembrane transport. In addition, interweaved networks were constructed to show that the development of TBI might be affected by metabolite-related proteins and their protein pathways. CONCLUSION:The overall results show that acute TBI is susceptible to metabolic disorders, and the joint metabolite-protein network analysis provides a favorable prediction of TBI pathogenesis mechanisms in the brain. The signatures in the hippocampus might be promising for the development of biomarkers and pathways relevant to acute TBI and could further guide testable predictions of the underlying mechanism of TBI.

Dataset Information

Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in rats with acute traumatic brain injury.

Publications

Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in rats with acute traumatic brain injury.

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