Peripheral immune activation could cause neuroinflammation, leading to a series of central nervous system (CNS) disorders, such as spatial learning and memory dysfunction. However, its pathogenic mechanism and therapeutic strategies are not yet determined. The present study aimed to investigate the therapeutic effects of sulforaphane (SFN) on lipopolysaccharide (LPS)-induced spatial learning and memory dysfunction, and tried to elucidate its relationship with the role of hippocampal brain-derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling pathway. Intraperitoneal injection of LPS for consecutive 7 days to mice caused abnormal behaviors in Morris water maze test (MWMT), while systemic administration of SFN notably reversed the abnormal behaviors. In addition, hippocampal levels of inflammatory cytokines, synaptic proteins, BDNF-tropomyosin receptor kinase B (TrkB) and mTOR signaling pathways were altered in the processes of LPS-induced cognitive dysfunction and SFN's therapeutic effects. Furthermore, we found that ANA-12 (a TrkB inhibitor) or rapamycin (a mTOR inhibitor) could block the beneficial effects of SFN on LPS-induced cognitive dysfunction, and that hippocampal levels of synaptic proteins, BDNF-TrkB and mTOR signaling pathways were also notably changed. In conclusion, the results of the present study suggest that SFN could elicit improving effects on LPS-induced spatial learning and memory dysfunction, which is likely related to the regulation of hippocampal BDNF-mTOR signaling pathway. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.