Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation

Abstract Objective Dimethyl fumarate (DMF) has been reported to exert a protective role against diverse lung diseases and cognitive impairment-related diseases. Thus this study aimed to investigate its role on acute lung injury (ALI) and related cognitive impairment in animal model. Methods C57BL/6...

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Autores principales:	Xiaowei Wang, Yanbo Wang, Haiyan Pan, Ci Yan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Acute lung injury Dimethyl fumarate Inflammation Cognitive deficits Surgery RD1-811 Anesthesiology RD78.3-87.3
Acceso en línea:	https://doaj.org/article/2c364684f8b64b86899ea60757013067
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spelling	oai:doaj.org-article:2c364684f8b64b86899ea607570130672021-11-14T12:33:57ZDimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation10.1186/s13019-021-01705-61749-8090https://doaj.org/article/2c364684f8b64b86899ea607570130672021-11-01T00:00:00Zhttps://doi.org/10.1186/s13019-021-01705-6https://doaj.org/toc/1749-8090Abstract Objective Dimethyl fumarate (DMF) has been reported to exert a protective role against diverse lung diseases and cognitive impairment-related diseases. Thus this study aimed to investigate its role on acute lung injury (ALI) and related cognitive impairment in animal model. Methods C57BL/6 mice were divided into four groups: control group, DMF group, ALI group, and ALI + DMF group. For ALI group, the ALI mice model was created by airway injection of LPS (50 μL, 1 μg/μL); for ALI + DMF group, DMF (dissolved in 0.08% methylcellulose) was treated twice a day for 2 days, and on the third day, mice were injected with LPS for ALI modeling. Mice pre-administered with methylcellulose or DMF without LPS injection (PBS instead) were used as the control group and DMF group, respectively. Morris water maze test was performed before any treatment (0 h) and 6 h after LPS-induction (54 h) to evaluate the cognitive impairment of mice. Next, the brain edema and blood brain barrier (BBB) permeability of ALI mice were assessed by brain water content, Evans blue extravasation and FITC-Dextran uptake assays. In addition, the effect of DMF on the numbers of total cells and neutrophils, protein content in BALF were quantified; the inflammatory factors in BALF, serum, and brain tissues were examined by ELISA, qRT-PCR, and Western blot assays. The effect of DMF on the cognitive impairment-related factor HIF-1α level in lung and brain tissues was also examined by Western blot. Results DMF reduced the numbers of total cells, neutrophils and protein content in BALF of ALI mice, inhibited the levels of IL-6, TNF-α and IL-1β in BALF, serum and brain tissues of ALI mice. The protein expressions of p-NF-κB/NF-κB and p-IKBα/IKBα was also suppressed by DMF in ALI mice. Morris water maze test showed that DMF alleviated the cognitive impairment in ALI mice by reducing the escape latency and path length. Moreover, DMF lessened the BBB permeability by decreasing cerebral water content, Evans blue extravasation and FITC-Dextran uptake in ALI mice. The HIF-1α levels in lung and brain tissues of ALI mice were also lessened by DMF. Conclusion In conclusion, DME had the ability to alleviate the lung injury and cerebral cognitive impairment in ALI model mice. This protective effect partly associated with the suppression of inflammation by DMF.Xiaowei WangYanbo WangHaiyan PanCi YanBMCarticleAcute lung injuryDimethyl fumarateInflammationCognitive deficitsSurgeryRD1-811AnesthesiologyRD78.3-87.3ENJournal of Cardiothoracic Surgery, Vol 16, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acute lung injury Dimethyl fumarate Inflammation Cognitive deficits Surgery RD1-811 Anesthesiology RD78.3-87.3
spellingShingle	Acute lung injury Dimethyl fumarate Inflammation Cognitive deficits Surgery RD1-811 Anesthesiology RD78.3-87.3 Xiaowei Wang Yanbo Wang Haiyan Pan Ci Yan Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation
description	Abstract Objective Dimethyl fumarate (DMF) has been reported to exert a protective role against diverse lung diseases and cognitive impairment-related diseases. Thus this study aimed to investigate its role on acute lung injury (ALI) and related cognitive impairment in animal model. Methods C57BL/6 mice were divided into four groups: control group, DMF group, ALI group, and ALI + DMF group. For ALI group, the ALI mice model was created by airway injection of LPS (50 μL, 1 μg/μL); for ALI + DMF group, DMF (dissolved in 0.08% methylcellulose) was treated twice a day for 2 days, and on the third day, mice were injected with LPS for ALI modeling. Mice pre-administered with methylcellulose or DMF without LPS injection (PBS instead) were used as the control group and DMF group, respectively. Morris water maze test was performed before any treatment (0 h) and 6 h after LPS-induction (54 h) to evaluate the cognitive impairment of mice. Next, the brain edema and blood brain barrier (BBB) permeability of ALI mice were assessed by brain water content, Evans blue extravasation and FITC-Dextran uptake assays. In addition, the effect of DMF on the numbers of total cells and neutrophils, protein content in BALF were quantified; the inflammatory factors in BALF, serum, and brain tissues were examined by ELISA, qRT-PCR, and Western blot assays. The effect of DMF on the cognitive impairment-related factor HIF-1α level in lung and brain tissues was also examined by Western blot. Results DMF reduced the numbers of total cells, neutrophils and protein content in BALF of ALI mice, inhibited the levels of IL-6, TNF-α and IL-1β in BALF, serum and brain tissues of ALI mice. The protein expressions of p-NF-κB/NF-κB and p-IKBα/IKBα was also suppressed by DMF in ALI mice. Morris water maze test showed that DMF alleviated the cognitive impairment in ALI mice by reducing the escape latency and path length. Moreover, DMF lessened the BBB permeability by decreasing cerebral water content, Evans blue extravasation and FITC-Dextran uptake in ALI mice. The HIF-1α levels in lung and brain tissues of ALI mice were also lessened by DMF. Conclusion In conclusion, DME had the ability to alleviate the lung injury and cerebral cognitive impairment in ALI model mice. This protective effect partly associated with the suppression of inflammation by DMF.
format	article
author	Xiaowei Wang Yanbo Wang Haiyan Pan Ci Yan
author_facet	Xiaowei Wang Yanbo Wang Haiyan Pan Ci Yan
author_sort	Xiaowei Wang
title	Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation
title_short	Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation
title_full	Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation
title_fullStr	Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation
title_full_unstemmed	Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation
title_sort	dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation
publisher	BMC
publishDate	2021
url	https://doaj.org/article/2c364684f8b64b86899ea60757013067
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_version_	1718429156762451968

Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation

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