Objective: Hydrogen sulfide (H2S), as a novel gasotransmitter, plays important roles in a number of physiological and pathological processes. Its effectiveness has been demonstrated in different types of brain disorders but not in repetitive febrile seizure (febrile status epilepticus; FSE) models. This study aims to test whether a donor of H2S sodium sulfhydrate (NaHS) is also effective for FSE in rats. Methods: FSE was induced in rat pups on postnatal day 10 in water at 45.0 ± 0.1°C for 10 consecutive days with or without preadministration of NaHS. Following evaluation of the latency and duration of hyperthermic seizures, impairment in learning and memory was measured by the Morris water maze test. Moreover, alterations of the microglial response and the production of proinflammatory cytokines IL-1β and TNF-α were calculated in the hippocampus. Results: We found that NaHS significantly increased the latency and decreased the duration of hyperthermic seizures. Furthermore, NaHS-treated pups showed less impairment in learning and memory. In addition, NaHS inhibited FSE-induced microglial responses and suppressed the production of IL-1β and TNF-α in the hippocampus. Conclusion: NaHS appears to be effective for the treatment of FSE in infants and children, in part due to its anti-inflammatory action.

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