ChengPing Bai* and ChenLiang Zhao Pages 156 - 165 ( 10 )
Introduction: The effect of hydrogen sulfide (H2S) on global cerebral ischemia remains partially understood. This study aimed to investigate the neuroprotective effect of sodium hydrosulfide (NaHS, a donor of H2S) post-conditioning and its underlying mechanism in a transient global cerebral ischemia (tGCI) model.
Materials & Methods: The tGCI rat model was established by the four-vessel occlusion method. Wistar rats were randomly assigned into 6 groups: sham, tGCI, tGCI +NaHS, tGCI+vehicle, tGCI+U0126 and tGCI+U0126+NaHS groups. Neurons survival was assessed by Nissl staining and NeuN immunostaining. Levels of extracellular extracellular-regulated kinases (ERK)1/2 and p-ERK1/2 were determined by western blot and immunohistochemistry (IHC). Intraperitoneal injection of NaHS (24 µmol/kg) at 24 h post-tGCI attenuated tGCI-induced decrease of the survival and NeuN-positive neurons in the hippocampal CA1 subregion.
Results: Compared to the sham group, tGCI significantly up-regulated p-ERK1/2 protein at 26 and 48 h post-tGCI. NaHS post-conditioning further enhanced the phosphorylation of ERK1/2 at 26, 48 and 168 h post-tGCI. Nevertheless, U0126 (an inhibitor of MEK1/2) pre-treatment reduced the p-ERK1/2 level in both the tGCI+ U0126 group and the tGCI+ U0126+ NaHS group. IHC staining revealed that p-ERK1/2-positive cell could be observed in several hippocampal subregions of the rats receiving NaHS post-conditioning. Immunofluorescence staining showed that some neurons were double-stained with p-ERK1/2 and NeuN. Furthermore, U0126 pre-treatment significantly attenuated the protective effect of NaHS post-conditioning on the neurons survival and NeuNpositive neurons in CA1 subregion.
Conclusion: These results suggested that NaHS post-conditioning can protect hippocampal CA1 neurons from tGCI-induced injury, at least partially, through activation of ERK1/2 signaling.
Hydrogen sulfide, neuroprotection, transient global cerebral ischemia (tGCI), ischemic stroke, extracellular signalregulated kinases 1 and 2 (ERK1/2).
Department of Neurology, Affiliated Hospital of Qinghai University, 810001, Xining, Qinghai, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, Zhejiang