Cheng Ping Bai *, ChenLiang Zhao and Lijuan Shen Pages 397 - 405 ( 9 )
Background: Although the neuroprotective effect of sodium hydrosulfide (NaHS, a hydrogen sulfide donor) pretreatment has been revealed, the effect of NaHS post-conditioning remains largely unknown.
Objective: We aimed to investigate the neuroprotective effect of NaHS post-conditioning against transient Global Cerebral Ischemia (tGCI)-induced hippocampal CA1 injury and its underlying molecular mechanism.
Methods: A tGCI rat model was established using the four-vessel occlusion method for 15 min of ischemia. The survival of hippocampal neurons was determined by Nissl staining and NeuN immunostaining. Protein expression of potassium voltage-gated channel subfamily D member 2 (Kv4.2) and potassium channel interacting protein 3 (KChIP3) was assessed by Immunohistochemistry (IHC) and Western blot.
Results: Decreased concentrations (12 and 24 µmol/kg) of NaHS post-conditioning significantly increased the numbers of survival neurons and NeuN-positive neurons in the hippocampal CA1 region at 7 days post-tGCI (all P<0.05). NaHS post-conditioning (24 µmol/kg) at 12 and 24 hr posttGCI can achieve the best protective effect (both P<0.05). IHC data demonstrated that NaHS postconditioning (24 µmol/kg) markedly attenuated tGCI-induced down-regulation of Kv4.2 protein in the hippocampal CA1 region at 26 hr post-tGCI. Confocal images showed that Kv4.2 did not express in the neuronal nuclei but predominantly express in the neuronal dendrites. In addition, NaHS post-conditioning significantly up-regulated Kv4.2 and down-regulated KChIP3 in tGCI rats at 26 and 168 hr post- tGCI (all P<0.05).
Conclusion: Decreased concentrations of NaHS post-conditioning at 12-24 hr post-tGCI effectively protected hippocampal CA1 neurons from tGCI-induced injury, which may be through regulating the expression of Kv4.2 and KChIP3.
Transient global cerebral ischemia, hippocampal CA1 region, neuroprotection, sodium hydrosulfide, postconditioning, Kv4.2, KChIP3.
Department of Neurology, Affiliated Hospital of Qinghai University, 810001, Xining, Qinghai, Department of Critical Care Medicine, The Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang, Department of Gastroenterology, Affiliated Hospital of Qinghai University, 810001, Xining, Qinghai