Key result
Hydrogen sulfide reduces infarct area ~35% in animal stroke models, but high bias limits translation.
Why the study?
This study aimed to determine whether preclinical evidence is sufficient to guide the initiation of clinical stroke trials with hydrogen sulfide (H 2 S) and to provide design recommendations.
Does hydrogen sulfide improve structural and functional outcomes in animal models of ischemic stroke?
Meta-Analysis (n=640)
Does hydrogen sulfide improve structural and functional outcomes in animal models of ischemic stroke?
Effect estimate: 34.5% reduction (95% CI 28.2-40.8%)
p-value: p=<0.0001
Although H2S reduces infarct area and neurological deficits in animal models of ischemic stroke, the preclinical evidence is of low quality and insufficient to proceed to clinical trials.
Hypothesis-generating for hydrogen sulfide neuroprotection; high bias leaves clinical translation open.
Hydrogen sulfide (H 2 S) is a gasotransmitter that has been studied for its potential therapeutic effects, including its role in the pathophysiology and treatment of stroke. This systematic review and meta-analysis aimed to determine the sufficiency of overall preclinical evidence to guide the initiation of clinical stroke trials with H 2 S and provide tailored recommendations for their design. PubMed, Web of Science, Scopus, EMBASE, and MEDLINE were searched for studies evaluating the effect of any H 2 S donor on in vivo animal models of regional ischemic stroke, and 34 publications were identified. Pooling of the effect sizes using the random-effect model revealed that H 2 S decreased the infarct area by 34.5% (95% confidence interval (CI) 28.2–40.8%, p < 0.0001), with substantial variability among the studies ( I 2 = 89.8%). H 2 S also caused a 37.9% reduction in the neurological deficit score (95% CI 29.0–46.8%, p < 0.0001, I 2 = 63.8%) and in the brain water content (3.2%, 95% CI 1.4–4.9%, p = 0.0014, I 2 = 94.6%). Overall, the studies had a high risk of bias and low quality of evidence (median quality score 5/15, interquartile range 4–9). The majority of the included studies had a “high” or “unclear” risk of bias, and none of the studies overall had a “low” risk. In conclusion, H 2 S significantly improves structural and functional outcomes in in vivo animal models of ischemic stroke. However, the level of evidence from preclinical studies is not sufficient to proceed to clinical trials due to the low external validity, high risk of bias, and variable design of existing animal studies.
No takes yet. Share an insight, caveat, or question.
Aydıngöz et al. (2024) conducted a meta-analysis in Ischemic stroke (animal models) (n=640). Hydrogen sulfide (H2S) donors vs. No treatment / control was evaluated on Infarct area (34.5% reduction, 95% CI 28.2-40.8%, p=<0.0001). Hydrogen sulfide decreased the infarct area by 34.5% compared to control in in vivo animal models of ischemic stroke, though high risk of bias limits translation to clinical trials.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: