NMR analysis of the rat neurochemical changes induced by middle cerebral artery occlusion

Stroke is a leading cause of death and disability, affecting millions of people worldwide with almost 80% of them as ischemic stroke and understanding the multiple mechanisms underlying cerebral ischemia is essential for development of effective treatments. To understand metabolic changes induced by focal brain ischemia, we conducted a comparative analysis of metabolic composition of cerebral tissue from rats with sham-operation and middle cerebral artery occlusion (MCAO) using high-resolution nuclear magnetic resonance (NMR) spectroscopy. More than 40 metabolites were assigned including organic acids, amino acids, carbohydrates, choline, pyrimidine and purine metabolites. Our results showed that MCAO led to significant level decreases for glutamate, glutamine, aspartate, γ-aminobutyrate (GABA), taurine, malate, fumarate, acetate, phosphocreatine, and purine and pyrimidine metabolites such as inosine, hypoxanthine, xanthine, uracil and UDP/UTP, together with significant level increases for glucose in focal brain tissue extracts. This demonstrated that experimental ischemic stroke in rats caused extensive perturbation in tricarboxylic acid cycle, GABA shunt, and metabolisms of choline and nucleic acids. These findings provided essential information for our understandings of MCAO-caused biochemical alterations and demonstrated the metabolite composition analysis as a useful tool for understanding the neurochemistry of stroke.