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

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.