中文版 | English
Title

Secukinumab attenuates neuroinflammation and neurobehavior defect via PKCβ/ERK/NF-κB pathway in a rat model of GMH

Author
Corresponding AuthorGong,Ye; Tang,Jiping
Publication Years
2023-02-01
DOI
Source Title
ISSN
0014-4886
EISSN
1090-2430
Volume360
Abstract
Aims: Germinal matrix hemorrhage (GMH) is a disastrous clinical event for newborns. Neuroinflammation plays an important role in the development of neurological deficits after GMH. The purpose of this study is to investigate the anti-inflammatory role of secukinumab after GMH and its underlying mechanisms involving PKCβ/ERK/NF-κB signaling pathway. Methods: A total of 154 Sprague-Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. Secukinumab was administered intranasally post-GMH. PKCβ activator PMA and p-ERK activator Ceramide C6 were administered intracerebroventricularly at 24 h prior to GMH induction, respectively. Neurobehavioral tests, western blot and immunohistochemistry were used to evaluate the efficacy of Secukinumab in both short-term and long-term studies. Results: Endogenous IL-17A, IL-17RA, PKCβ and p-ERK were increased after GMH. Secukinumab treatment improved short- and long-term neurological outcomes, reduced the synthesis of MPO and Iba-1 in the perihematoma area, and inhibited the synthesis of proinflammatory factors, such as NF-κB, IL-1β, TNF-α and IL-6. Additionally, PMA and ceramide C6 abolished the beneficial effects of Secukinumab. Conclusion: Secukinumab treatment suppressed neuroinflammation and attenuated neurological deficits after GMH, which was mediated through the downregulation of the PKCβ/ERK/NF-κB pathway. Secukinumab treatment may provide a promising therapeutic strategy for GMH patients.
Keywords
URL[Source Record]
Indexed By
Language
English
SUSTech Authorship
First
Funding Project
National Institutes of Health[NS082184];National Institutes of Health[NS101284];
WOS Research Area
Neurosciences & Neurology
WOS Subject
Neurosciences
WOS Accession No
WOS:000895126300002
Publisher
ESI Research Field
NEUROSCIENCE & BEHAVIOR
Scopus EID
2-s2.0-85142367083
Data Source
Scopus
Citation statistics
Cited Times [WOS]:0
Document TypeJournal Article
Identifierhttp://kc.sustech.edu.cn/handle/2SGJ60CL/412530
DepartmentShenzhen People's Hospital
Affiliation
1.Department of Pediatrics,Shenzhen People's Hospital,The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology,China
2.Department of Critical Care Medicine,HuaShan Hospital,Fudan University,Shanghai,200040,China
3.Department of Physiology and Pharmacology,Center for Neuroscience Research,Loma Linda University School of Medicine,Loma Linda,92350,United States
4.Department of Neurosurgery,Loma Linda University School of Medicine,Loma Linda,92350,United States
5.Department of Anesthesiology,Loma Linda University School of Medicine,Loma Linda,92350,United States
6.Department of Neurosurgery,Huashan Hospital,Fudan University,Shanghai,200040,China
7.Department of Pediatrics,Shenzhen People's Hospital,The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology,Guangdong,China
First Author AffilicationShenzhen People's Hospital
First Author's First AffilicationShenzhen People's Hospital
Recommended Citation
GB/T 7714
Liu,Shengpeng,Deng,Shuixiang,Ding,Yan,et al. Secukinumab attenuates neuroinflammation and neurobehavior defect via PKCβ/ERK/NF-κB pathway in a rat model of GMH[J]. EXPERIMENTAL NEUROLOGY,2023,360.
APA
Liu,Shengpeng.,Deng,Shuixiang.,Ding,Yan.,Flores,Jerry J..,Zhang,Xiaoli.,...&Tang,Jiping.(2023).Secukinumab attenuates neuroinflammation and neurobehavior defect via PKCβ/ERK/NF-κB pathway in a rat model of GMH.EXPERIMENTAL NEUROLOGY,360.
MLA
Liu,Shengpeng,et al."Secukinumab attenuates neuroinflammation and neurobehavior defect via PKCβ/ERK/NF-κB pathway in a rat model of GMH".EXPERIMENTAL NEUROLOGY 360(2023).
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