Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage

The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more...

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Autores principales:	Syed Kashif Zaidi, Farid Ahmed, Heba Alkhatabi, Md Nasrul Hoda, Muhammad Al-Qahtani
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	diabetes thrombosis stroke GSNO IVT Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/97e37942949346cb8607360ffa77201c
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spelling	oai:doaj.org-article:97e37942949346cb8607360ffa77201c2021-11-25T16:52:25ZNebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage10.3390/biom111115872218-273Xhttps://doaj.org/article/97e37942949346cb8607360ffa77201c2021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1587https://doaj.org/toc/2218-273XThe COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of “clinically” relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, “IV-effects” of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 μg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.Syed Kashif ZaidiFarid AhmedHeba AlkhatabiMd Nasrul HodaMuhammad Al-QahtaniMDPI AGarticlediabetesthrombosisstrokeGSNOIVTMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1587, p 1587 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetes thrombosis stroke GSNO IVT Microbiology QR1-502
spellingShingle	diabetes thrombosis stroke GSNO IVT Microbiology QR1-502 Syed Kashif Zaidi Farid Ahmed Heba Alkhatabi Md Nasrul Hoda Muhammad Al-Qahtani Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage
description	The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of “clinically” relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, “IV-effects” of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 μg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.
format	article
author	Syed Kashif Zaidi Farid Ahmed Heba Alkhatabi Md Nasrul Hoda Muhammad Al-Qahtani
author_facet	Syed Kashif Zaidi Farid Ahmed Heba Alkhatabi Md Nasrul Hoda Muhammad Al-Qahtani
author_sort	Syed Kashif Zaidi
title	Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage
title_short	Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage
title_full	Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage
title_fullStr	Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage
title_full_unstemmed	Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage
title_sort	nebulization of low-dose s-nitrosoglutathione in diabetic stroke enhances benefits of reperfusion and prevents post-thrombolysis hemorrhage
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/97e37942949346cb8607360ffa77201c
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Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage

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