Metabolomic investigation of regional brain tissue dysfunctions induced by global cerebral ischemia

Tianshu Zhang, Wei Wang, Jin Huang, Xia Liu, Haiyan Zhang, Naixia Zhang

To get a broader view of global ischemia-induced cerebral disorders at the metabolic level, a nuclear magnetic resonance-based metabolomic study was performed to evaluate the metabolic profile changes on regional brain tissues of female and male mice upon bilateral common carotid arteries occlusion (BCCAO) operation. Significant metabolic disorders were observed in both cerebral cortex and hippocampus tissues of the experimental mice upon global cerebral ischemic attack. Multiple amino acids were identified as the dominantly perturbed metabolites. It was also shown that although the metabolic profile change patterns in the brain tissues were quite similar in male and female BCCAO mice, metabolic disorders in the cortex tissues were more severe in the female mice than in the male mice. In the present study, significant changes in amino acid metabolic pathways were confirmed in the early stage of global ischemia. Meanwhile, cerebral metabolic dysfunctions were more severe in the female BCCAO mice than in the male mice, suggesting that gender may play a role in different metabolic responses to the ischemic attack, which may provide an important hypothesis for a better understanding of the clinically observed gender-dependent pathological outcome of cerebral ischemia.