摘要Background : Hippocampal damage caused by status epilepticus (SE) can bring about cognitive decline and emotional disorders, which are common clinical comorbidities in patients with epilepsy. It is therefore imperative to develop a novel therapeutic strat-egy for protecting hippocampal damage after SE. Mitochondrial dysfunction is one of contributing factors in epilepsy. Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria, we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.Methods : Pilocarpine was used to induced SE in mice. SE- generated cognitive de-cline and emotional disorders were determined using novel object recognition, the tail suspension test, and the open field test. SE-i nduced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes. The metabolites underlying mitochondrial transplantation were determined using metabonomics. Results : The results showed that peripheral administration of isolated mitochon-dria could improve cognitive deficits and depressive and anxiety-l ike behaviors. Exogenous mitochondria blunted the production of reactive oxygen species, pro-liferation of microglia and astrocytes, and loss of neurons in the hippocampus. The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism. Among potential affected metabolites, mitochondrial transplantation decreased levels of sphingolipid (d18:1/18:0) and methylmalonic acid, and elevated levels of D- fructose- 1,6- bisphosphate. Conclusion : To the best of our knowledge, these findings provide the first direct ex-perimental evidence that artificial mitochondrial transplantation is capable of amelio-rating hippocampal damage following SE. These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy- associated psychiat-ric and cognitive disorders.