Cargando…
Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-κB Pathway
Background and Purpose: Neuroinflammation has been shown to play a critical role in secondary craniocerebral injury, leading to poor outcomes for TBI patients. Abrocitinib, a Janus kinase1 (JAK1) selective inhibitor approved to treat atopic dermatitis (AD) by the Food and Drug Administration (FDA),...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688110/ https://www.ncbi.nlm.nih.gov/pubmed/36429017 http://dx.doi.org/10.3390/cells11223588 |
_version_ | 1784836184081432576 |
---|---|
author | Li, Tuo Li, Lei Peng, Ruilong Hao, Hongying Zhang, Hejun Gao, Yalong Wang, Cong Li, Fanjian Liu, Xilei Chen, Fanglian Zhang, Shu Zhang, Jianning |
author_facet | Li, Tuo Li, Lei Peng, Ruilong Hao, Hongying Zhang, Hejun Gao, Yalong Wang, Cong Li, Fanjian Liu, Xilei Chen, Fanglian Zhang, Shu Zhang, Jianning |
author_sort | Li, Tuo |
collection | PubMed |
description | Background and Purpose: Neuroinflammation has been shown to play a critical role in secondary craniocerebral injury, leading to poor outcomes for TBI patients. Abrocitinib, a Janus kinase1 (JAK1) selective inhibitor approved to treat atopic dermatitis (AD) by the Food and Drug Administration (FDA), possesses a novel anti-inflammatory effect. In this study, we investigated whether abrocitinib could ameliorate neuroinflammation and exert a neuroprotective effect in traumatic brain injury (TBI) models. Methods: First, next-generation sequencing (NGS) was used to select genes closely related to neuroinflammation after TBI. Then, magnetic resonance imaging (MRI) was used to dynamically observe the changes in traumatic focus on the 1st, 3rd, and 7th days after the induction of fluid percussion injury (FPI). Moreover, abrocitinib’s effects on neurobehaviors were evaluated. A routine peripheral blood test was carried out and Evans blue dye extravasation, cerebral cortical blood flow, the levels of inflammatory cytokines, and changes in the numbers of inflammatory cells were evaluated to investigate the function of abrocitinib on the 1st day post-injury. Furthermore, the JAK1/signal transducer and activator of transcription1 (STAT1)/nuclear factor kappa (NF-κB) pathway was assessed. Results: In vivo, abrocitinib treatment was found to shrink the trauma lesions. Compared to the TBI group, the abrocitinib treatment group showed better neurological function, less blood-brain barrier (BBB) leakage, improved intracranial blood flow, relieved inflammatory cell infiltration, and reduced levels of inflammatory cytokines. In vitro, abrocitinib treatment was shown to reduce the pro-inflammatory M1 microglia phenotype and shift microglial polarization toward the anti-inflammatory M2 phenotype. The WB and IHC results showed that abrocitinib played a neuroprotective role by restraining JAK1/STAT1/NF-κB levels after TBI. Conclusions: Collectively, abrocitinib treatment after TBI is accompanied by improvements in neurological function consistent with radiological, histopathological, and biochemical changes. Therefore, abrocitinib can indeed reduce excessive neuroinflammation by restraining the JAK1/STAT1/NF-κB pathway. |
format | Online Article Text |
id | pubmed-9688110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96881102022-11-25 Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-κB Pathway Li, Tuo Li, Lei Peng, Ruilong Hao, Hongying Zhang, Hejun Gao, Yalong Wang, Cong Li, Fanjian Liu, Xilei Chen, Fanglian Zhang, Shu Zhang, Jianning Cells Article Background and Purpose: Neuroinflammation has been shown to play a critical role in secondary craniocerebral injury, leading to poor outcomes for TBI patients. Abrocitinib, a Janus kinase1 (JAK1) selective inhibitor approved to treat atopic dermatitis (AD) by the Food and Drug Administration (FDA), possesses a novel anti-inflammatory effect. In this study, we investigated whether abrocitinib could ameliorate neuroinflammation and exert a neuroprotective effect in traumatic brain injury (TBI) models. Methods: First, next-generation sequencing (NGS) was used to select genes closely related to neuroinflammation after TBI. Then, magnetic resonance imaging (MRI) was used to dynamically observe the changes in traumatic focus on the 1st, 3rd, and 7th days after the induction of fluid percussion injury (FPI). Moreover, abrocitinib’s effects on neurobehaviors were evaluated. A routine peripheral blood test was carried out and Evans blue dye extravasation, cerebral cortical blood flow, the levels of inflammatory cytokines, and changes in the numbers of inflammatory cells were evaluated to investigate the function of abrocitinib on the 1st day post-injury. Furthermore, the JAK1/signal transducer and activator of transcription1 (STAT1)/nuclear factor kappa (NF-κB) pathway was assessed. Results: In vivo, abrocitinib treatment was found to shrink the trauma lesions. Compared to the TBI group, the abrocitinib treatment group showed better neurological function, less blood-brain barrier (BBB) leakage, improved intracranial blood flow, relieved inflammatory cell infiltration, and reduced levels of inflammatory cytokines. In vitro, abrocitinib treatment was shown to reduce the pro-inflammatory M1 microglia phenotype and shift microglial polarization toward the anti-inflammatory M2 phenotype. The WB and IHC results showed that abrocitinib played a neuroprotective role by restraining JAK1/STAT1/NF-κB levels after TBI. Conclusions: Collectively, abrocitinib treatment after TBI is accompanied by improvements in neurological function consistent with radiological, histopathological, and biochemical changes. Therefore, abrocitinib can indeed reduce excessive neuroinflammation by restraining the JAK1/STAT1/NF-κB pathway. MDPI 2022-11-13 /pmc/articles/PMC9688110/ /pubmed/36429017 http://dx.doi.org/10.3390/cells11223588 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Tuo Li, Lei Peng, Ruilong Hao, Hongying Zhang, Hejun Gao, Yalong Wang, Cong Li, Fanjian Liu, Xilei Chen, Fanglian Zhang, Shu Zhang, Jianning Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-κB Pathway |
title | Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-κB Pathway |
title_full | Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-κB Pathway |
title_fullStr | Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-κB Pathway |
title_full_unstemmed | Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-κB Pathway |
title_short | Abrocitinib Attenuates Microglia-Mediated Neuroinflammation after Traumatic Brain Injury via Inhibiting the JAK1/STAT1/NF-κB Pathway |
title_sort | abrocitinib attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting the jak1/stat1/nf-κb pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688110/ https://www.ncbi.nlm.nih.gov/pubmed/36429017 http://dx.doi.org/10.3390/cells11223588 |
work_keys_str_mv | AT lituo abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT lilei abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT pengruilong abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT haohongying abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT zhanghejun abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT gaoyalong abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT wangcong abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT lifanjian abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT liuxilei abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT chenfanglian abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT zhangshu abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway AT zhangjianning abrocitinibattenuatesmicrogliamediatedneuroinflammationaftertraumaticbraininjuryviainhibitingthejak1stat1nfkbpathway |