Hypoxic encephalopathy is a common cause of neonatal
seizures and long-term neurological abnormalities. Endogenous
hydrogen sulfide (H2S) may have multiple functions in brain. The aim of this study is to investigate whether
sodium hydrosulfide (
NaHS), a H2S donor, provides protection against neonatal
hypoxia-induced neurobehavioral deficits. Neonatal mice were subjected to
hypoxia (5%
oxygen for 120min) at postnatal day 1 and received
NaHS (5.6mg/kg) once daily for 3d. Neurobehavioral toxicity was examined at 3-30d after
hypoxia. Treatment with
NaHS significantly attenuated the delayed development of sensory and motor reflexes induced by
hypoxia up to two weeks after the insult. Moreover,
NaHS improved the learning and memory performance of hypoxic animals as indicated in Morris water maze test at 30d after
hypoxia. In mice exposed to
hypoxia, treatment with
NaHS enhanced expression of
brain derived neurotrophic factor (
BDNF) in the hippocampus. Furthermore, the protective effects of
NaHS were associated with its ability to repress the
hypoxia-induced
nitric oxide synthase (NOS) activity and
nitric oxide production in the hippocampus of mice brain. Taken together, these results suggest that the long-lasting beneficial effects of
NaHS on
hypoxia-induced neurobehavioral deficits are mediated, at least in part, by inducing
BDNF expression and suppressing NOS activity in the brain of mice.