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Local and systemic metabolic alterations in brain, plasma, and liver of rats in response to aging and ischemic stroke, as detected by nuclear magnetic resonance (NMR) spectroscopy

ABSTRACT: Cerebral ischemia and aging induce local and systemic effects, and impact severity of stroke outcome. We performed comprehensive metabolic profiling to detect metabolites in brain, plasma, and liver as a function of aging and ischemia/reperfusion (IR). Ischemic stroke was induced by middle cerebral artery occlusion. Abundant metabolites were identified and quantified by 1H-NMR. Older rats aged 12 months showed significant changes in metabolic profiles in the brain, but only a few metabolites were changed in the liver and plasma as compared to younger rats aged 3 months. However, I/R injury at day 2 resulted in major changes in metabolites in liver and plasma of older rats. In younger rats, focal cerebral ischemia induced reperfusion-time dependent changes in metabolites in brain, plasma, and liver. Metabolic changes were seen in brain as early as day 2 of I/R, plasma showed significant changes at day 3 of reperfusion, and liver exhibited delayed response after day 3 that continued to remain at week 2 of reperfusion-time. Pathways involved in energy and amino acid metabolism, inflammation, and oxidative stress were altered as a result of aging and I/R. Thus, age, tissue, and I/R time affect changes in metabolites and may have implications in stroke outcome.

INSTRUMENT(S): Bruker

SUBMITTER: Vijesh Bhute

PROVIDER: MTBLS516 | MetaboLights | 2019-02-01

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS516	Other
	FILES	Other
	a_MTBLS516_rat_stroke_metabolite_profiling_NMR_spectroscopy.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS516_rat_stroke_metabolite_profiling_NMR_spectroscopy_v2_maf.tsv	Tabular

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Project description:Cerebral ischemia/reperfusion injury (CI/RI), including neurological behavior deficits, cerebral infarction, blood-brain barrier (BBB) dysfunction, and neuroinflammation, et al. is a severe challenge in treatment of ischemic stroke. Traditional Chinese medicine (TCM) with the characteristics of multi-components and multi-functions for multiple targets/pathways has been historically used in the treatment of stroke and post stroke recovery in China. QiShenYiQi (QSYQ), a representative component-based Chinese medicine, is capable of reducing organ injury caused by ischemia/reperfusion via multiple mechanisms. Recently, we have previously reported that the positive action of QSYQ against the acute phase of CI/RI is partly via modulation of neuroinflammatory response. However, the effects and underlying mechanisms of QSYQ on subacute phase of CI/RI remain unknown, which are aimed to investigate in present study. The pharmacological action of QSYQ treatment on brain damage was estimated in the experimental stroke rats underwent 90 min ischemia and 8 days reperfusion by assessing the neurological and locomotor deficits, cerebral infarction, brain edema, and BBB integrity. Furthermore, we used TMT-based quantitative proteomics technology to identify significantly differentially expressed proteins following QSYQ treatment, which could give important clues for revealing the possible mechanism underlying the positive role of QSYQ in CI/RI. Besides, immunohistochemistry, western blot analysis, RT-qPCR, and rat ELISA kits were executed to further verify the accuracy of proteomics analysis results. As a consequence, we found that treatment with QSYQ (600mg/kg) for 7 days obviously improved neurological and behavioral impairment, attenuated infarct volume and brain edema, and alleviated BBB breakdown in stroke rats. Bioinformatics analysis suggested that differentially expressed protein galectin-3 mediated inflammatory response was closely related to the beneficial effect of QSYQ. Results of immunohistochemistry, western blot analysis and RT-qPCR showed that the model rats treated with QSYQ (600mg/kg) markedly downregulated the mRNA and protein expression level of galectin-3 in brain tissues compared to the untreated stroke rats. In addition, the decrease of mRNA level in brain tissues and contents in serum of TNF-α and IL-6 following QSYQ treatment were also observed. These interesting finding manifested that the effective action of QSYQ against subacute phase of CI/RI was partly via regulating galectin-3 mediated inflammatory reaction.

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Local and systemic metabolic alterations in brain, plasma, and liver of rats in response to aging and ischemic stroke, as detected by nuclear magnetic resonance (NMR) spectroscopy

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