Investigation of long-term metabolic alteration after stroke in tMCAO (transient middle cerebral artery occlusion) mouse model using metabolomics approach.

Stroke causes serious long-term disability and numerous molecular changes, including inflammation, depression, and immunosuppression. Despite this, the underlying metabolic mechanisms of poststroke complications remain unclear, and assessing metabolic changes may be beneficial. In this study, we investigated the changes in brain damage and long-term metabolic changes caused by stroke in a transient middle cerebral artery occlusion (tMCAO) mouse model. Metabolic profiling was conducted using UPLC-Orbitrap-MS/MS to compare the metabolites that changed 1 day, 1 week, 1 month, and 6 months after stroke. tMCAO caused an infarction that peaked at 1 week, following which atrophy was observed up to 6 months along with metabolomic changes. From the metabolomics analysis, 72 important metabolites associated with poststroke were identified, and the changes in their levels were most at 1 day and less significant at 1 week followed by a significant change 6 months after stroke. Fatty acids, corticosterone, tyrosine, and tryptophan metabolites are involved in immunosuppression and inflammation. These results indicated that the change in metabolic level after stroke was persistent and could be associated with poststroke complications, such as brain atrophy. Therefore, it was concluded that long-term metabolic changes could involve the chronic after-effects of ischemic stroke.