Inhalative as well as Intravenous Administration of H 2 S Provides Neuroprotection after Ischemia and Reperfusion Injury in the Rats' Retina.

Background: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (H ₂ S) is considered a potentially neuroprotective substance, but the most effective route of application and the underlying mechanism remain to be determined.
Methods: Ischemia-reperfusion injury was induced in rats by a temporary increase in intraocular pressure (1 h). H ₂ S was then applied by inhalation (80 ppm at 0, 1.5, and 3 h after reperfusion) or by intravenous administration of the slow-releasing H ₂ S donor GYY 4137. After 24 h, the retinas were harvested for Western blotting, qPCR, and immunohistochemical staining. Retinal ganglion cell survival was evaluated 7 days after ischemia.
Results: Both inhalative and intravenously delivered H ₂ S reduced retinal ganglion cell death with a better result from inhalative application. H ₂ S inhalation for 1.5 h, as well as GYY 4137 treatment, increased p38 phosphorylation. Both forms of application enhanced the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhalation showed a significant increase at all three time points. H ₂ S treatment also reduced apoptotic and inflammatory markers, such as caspase-3, intracellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). The protective effect of H ₂ S was partly abolished by the ERK1/2 inhibitor PD98059. Inhalative H ₂ S also reduced the heat shock response including heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) and the expression of radical scavengers such as superoxide dismutases (SOD1, SOD2) and catalase.
Conclusion: Hydrogen sulfide acts, at least in part, via the mitogen-activated protein kinase (MAPK) ERK1/2 to reduce apoptosis and inflammation. Both inhalative H ₂ S and intravenous GYY 4137 administrations can improve neuronal cell survival.