Investigation of S-Nitrosoglutathione in stroke: A systematic review and meta-analysis of literature in pre-clinical and clinical research

Shimeng Liu; Haiqing Zheng; Wengui Yu; Viswanathan Ramakrishnan; Shreyansh Shah; Louis Fernando Gonzalez; Inderjit Singh; Carmelo Graffagnino; Wuwei Feng

doi:10.1016/j.expneurol.2020.113262

Investigation of S-Nitrosoglutathione in stroke: A systematic review and meta-analysis of literature in pre-clinical and clinical research

Exp Neurol. 2020 Jun:328:113262. doi: 10.1016/j.expneurol.2020.113262. Epub 2020 Feb 28.

Authors

Shimeng Liu¹, Haiqing Zheng², Wengui Yu³, Viswanathan Ramakrishnan⁴, Shreyansh Shah⁵, Louis Fernando Gonzalez⁶, Inderjit Singh⁷, Carmelo Graffagnino⁵, Wuwei Feng⁸

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China; Department of Neurology, University of California, Irvine, CA 92868, USA.
² Department of Physical Medicine and Rehabilitation, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
³ Department of Neurology, University of California, Irvine, CA 92868, USA.
⁴ Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
⁵ Department of Neurology, Duke University School of Medicine, Durham, NC, 27710, USA.
⁶ Department of Neurosurgery, Duke University School of Medicine, Durham, NC, 27710, USA.
⁷ Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
⁸ Department of Neurology, Duke University School of Medicine, Durham, NC, 27710, USA. Electronic address: wayne.feng@duke.edu.

PMID: 32119935
DOI: 10.1016/j.expneurol.2020.113262

Abstract

Background: S-Nitrosoglutathione (GSNO) is a nitric oxide donor that has been investigated for neuroprotective and neuro-recovery effect. We aimed to conduct a systematic review on the published literatures using GSNO in both pre-clinical and clinical stroke studies.

Methods: We searched PubMed up to June 30, 2019, using the following keywords: S-Nitrosoglutathione, GSNO, stroke, cerebrovascular, carotid arteries, middle cerebral artery, and middle cerebral artery occlusion. Only studies published in the English language providing efficacy results of GSNO on ischemic stroke were included. Stroke Therapy Academic Industry Roundtable (STAIR) score was used to assess the quality of pre-clinical studies and PEDro score for clinical trials. A meta-analysis was conducted to compare the effect size.

Results: Of 39 articles identified, 10 (6 for pre-clinical and 4 for clinical studies) met the eligibility criteria and were included. The median STAIR score across the pre-clinical studies was 5.5 (range: 4-7), and the median PEDro score for the 4 clinical trials was 10 (ranged: 6 to 10). Among the 6 pre-clinical studies, GSNO reduced infarct size in 6 studies and improved neurological behavior scales in 5 studies compared to placebo. Inverse-variance weighted linear meta-analysis of standardized mean difference (Hedge's g) on 4 human studies revealed a big effect size (Hedge's g = -0.82, 95% CI: [-1.26, -0.38], P = .0003) favoring the GSNO group in term of reducing embolic signals. I² value was 0 across the included clinical studies in the meta-analysis.

Conclusions: Pre-clinical studies showed positive benefit of GSNO in animal stroke models. The meta-analysis of clinical studies demonstrated that GSNO is effective in reducing embolic signals in patients with symptomatic internal carotid artery stenosis undergoing carotid endarterectomy or stenting. Further investigation of this molecule is warranted.

Keywords: Acute ischemic stroke; Neuroprotection; Nitric oxide; S-Nitrosoglutathione.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Animals
Brain / drug effects*
Humans
Neuroprotective Agents / pharmacology*
S-Nitrosoglutathione / pharmacology*
Stroke / drug therapy*

Substances

Neuroprotective Agents
S-Nitrosoglutathione