Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats

Abstract

Background: Hydrogen sulfide (H 2 S) has shown a neuroprotective role in several cerebrovascular diseases. This study aimed to explore the underlying mechanisms of H 2 S in early brain injury after subarachnoid hemorrhage (SAH). Methods: One hundred seventy-seven male Sprague-Dawley rats were employed in this study. Sodium hydrosulfide (NaHS), a donor of H 2 S, was injected intraperitoneally at 60 min after SAH was induced by endovascular perforation. Western blot analysis determined the expression of several proteins of interest, and an immunofluorescence assay was used to examine neuronal apoptosis. Results: Exogenous NaHS markedly improved neurological scores, attenuated brain edema, and ameliorated neuronal apoptosis at 24 h after SAH induction. The underlying mechanisms of H 2 S in ameliorating neuronal apoptosis might be executed through inhibition of the activity of mammalian sterile 20-like kinase 1 (MST1) protein. Western blot analysis demonstrated that exogenous NaHS decreased cleaved MST1 (cl-MST1) while increasing full-length MST1 expression. This anti-apoptotic effect of H 2 S could be reversed by chelerythrine, which could activate MST1 via caspase-dependent cleavage. Conclusions: Exogenous NaHS, as a donor of H 2 S, could ameliorate early brain injury after SAH by inhibiting neuronal apoptosis by reducing the activity of the MST1 protein.

RETRACTED: NOSH-NBP, a Novel Nitric Oxide and Hydrogen Sulfide- Releasing Hybrid, Attenuates Ischemic Stroke-Induced Neuroinflammatory Injury by Modulating Microglia Polarization

“…As the newest gasotransmitter, H 2 S is traditionally considered a poisonous gas and environmental pollutant. Evidence accumulated over the last decade reveals the potential value of H 2 S in the treatment of CNS diseases, including stroke and neurodegenerative diseases (Kida and Ichinose, 2015; Cui et al, 2016). Exogenous H 2 S donors confer neuroprotection in ischemic stroke, at least in part, owing to their anti-inflammatory properties (Yin et al, 2013).…”

SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage

“…These pathophysiological processes could further induce global ischemic injury. Oxidative stress has been observed to play a critical role in EBI [26]. A recent in vitro experiment demonstrated that the upregulated protein expression of SIRT3 in PC12 cells secondary to oxygen-glucose deprivation (OGD) was an endogenous feedback response for neuroprotection [27].…”

“…Due to its antioxidation function, SIRT3 is considered the potential therapeutic target for EBI [26]. Although the molecular mechanisms of SIRT3 function remain inadequate and controversial, its neuroprotective role was the primary focus of discussion in recent studies.…”

Neuroprotective Effects of a Smoothened Receptor Agonist against Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats

“…Neurological examinations of scoring system (Table 1) were blindly performed at 48 h after SAH according to previous research (Cui et al, 2015), monitoring three aspects: appetite, activity, and neurological deficits. Neurological deficits of the experimental animals were scored as follows: (i) “no neurologic deficit” scored as 0; (ii) “potential or minimum neurologic deficit” scored as 1; (iii) “mild neurologic deficits” scored as 2 or 3; (iv) “severe neurologic deficit” scored as 4–6.…”