Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPKHO-1PGC-1a Pathway in Neonatal Rats
Joint Authors
Zhao, Mingyi
Wang, Peipei
Chen, Zhiheng
Wu, Guojiao
Zhang, Chen
Zhou, Wenjuan
Zhao, Mengwen
Hirano, Shin-ichi
Zhao, Lingling
Fujino, Masayuki
Li, Xiao-Kang
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-02-13
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of death in neonates with no effective treatments.
Recent advancements in hydrogen (H2) gas offer a promising therapeutic approach for ischemia reperfusion injury; however, the impact of this approach for HIE remains a subject of debate.
We assessed the therapeutic effects of H2 gas on HIE and the underlying molecular mechanisms in a rat model of neonatal hypoxic-ischemic brain injury (HIBI).
H2 inhalation significantly attenuated neuronal injury and effectively improved early neurological outcomes in neonatal HIBI rats as well as learning and memory in adults.
This protective effect was associated with initiation time and duration of sustained H2 inhalation.
Furthermore, H2 inhalation reduced the expression of Bcl-2-associated X protein (BAX) and caspase-3 while promoting the expression of Bcl-2, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1 (HO-1).
H2 activated extracellular signal-regulated kinase and c-Jun N-terminal protein kinase and dephosphorylated p38 mitogen-activated protein kinase (MAPK) in oxygen-glucose deprivation/reperfusion (OGD/R) nerve growth factor-differentiated PC12 cells.
Inhibitors of MAPKs blocked H2-induced HO-1 expression.
HO-1 small interfering RNA decreased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and sirtuin 1 (SIRT1) and reversed the protectivity of H2 against OGD/R-induced cell death.
These findings suggest that H2 augments cellular antioxidant defense capacity through activation of MAPK signaling pathways, leading to HO-1 expression and subsequent upregulation of PGC-1α and SIRT-1 expression.
Thus, upregulation protects NGF-differentiated PC12 cells from OGD/R-induced oxidative cytotoxicity.
In conclusion, H2 inhalation exerted protective effects on neonatal rats with HIBI.
Early initiation and prolonged H2 inhalation had better protective effects on HIBI.
These effects of H2 may be related to antioxidant, antiapoptotic, and anti-inflammatory responses.
HO-1 plays an important role in H2-mediated protection through the MAPK/HO-1/PGC-1α pathway.
Our results support further assessment of H2 as a potential therapeutic for neurological conditions in which oxidative stress and apoptosis are implicated.
American Psychological Association (APA)
Wang, Peipei& Zhao, Mingyi& Chen, Zhiheng& Wu, Guojiao& Fujino, Masayuki& Zhang, Chen…[et al.]. 2020. Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPKHO-1PGC-1a Pathway in Neonatal Rats. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1205256
Modern Language Association (MLA)
Wang, Peipei…[et al.]. Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPKHO-1PGC-1a Pathway in Neonatal Rats. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-16.
https://search.emarefa.net/detail/BIM-1205256
American Medical Association (AMA)
Wang, Peipei& Zhao, Mingyi& Chen, Zhiheng& Wu, Guojiao& Fujino, Masayuki& Zhang, Chen…[et al.]. Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPKHO-1PGC-1a Pathway in Neonatal Rats. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1205256
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205256