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Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes
Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241405/ https://www.ncbi.nlm.nih.gov/pubmed/35799534 http://dx.doi.org/10.4103/1673-5374.344829 |
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author | Liu, Xi-Lei Sun, Dong-Dong Zheng, Mu-Tian Li, Xiao-Tian Niu, Han-Hong Zhang, Lan Zhou, Zi-Wei Rong, Hong-Tao Wang, Yi Wang, Ji-Wei Yang, Gui-Li Liu, Xiao Chen, Fang-Lian Zhou, Yuan Zhang, Shu Zhang, Jian-Ning |
author_facet | Liu, Xi-Lei Sun, Dong-Dong Zheng, Mu-Tian Li, Xiao-Tian Niu, Han-Hong Zhang, Lan Zhou, Zi-Wei Rong, Hong-Tao Wang, Yi Wang, Ji-Wei Yang, Gui-Li Liu, Xiao Chen, Fang-Lian Zhou, Yuan Zhang, Shu Zhang, Jian-Ning |
author_sort | Liu, Xi-Lei |
collection | PubMed |
description | Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days. Western blot, immunohistochemistry, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI. Our results suggest that maraviroc administration reduced NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation, modulated microglial polarization from M1 to M2, decreased neutrophil and macrophage infiltration, and inhibited the release of inflammatory factors after TBI. Moreover, maraviroc treatment decreased the activation of neurotoxic reactive astrocytes, which, in turn, exacerbated neuronal cell death. Additionally, we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score, rotarod test, Morris water maze test, and lesion volume measurements. In summary, our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI, and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI. |
format | Online Article Text |
id | pubmed-9241405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-92414052022-06-30 Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes Liu, Xi-Lei Sun, Dong-Dong Zheng, Mu-Tian Li, Xiao-Tian Niu, Han-Hong Zhang, Lan Zhou, Zi-Wei Rong, Hong-Tao Wang, Yi Wang, Ji-Wei Yang, Gui-Li Liu, Xiao Chen, Fang-Lian Zhou, Yuan Zhang, Shu Zhang, Jian-Ning Neural Regen Res Research Article Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days. Western blot, immunohistochemistry, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI. Our results suggest that maraviroc administration reduced NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation, modulated microglial polarization from M1 to M2, decreased neutrophil and macrophage infiltration, and inhibited the release of inflammatory factors after TBI. Moreover, maraviroc treatment decreased the activation of neurotoxic reactive astrocytes, which, in turn, exacerbated neuronal cell death. Additionally, we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score, rotarod test, Morris water maze test, and lesion volume measurements. In summary, our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI, and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI. Wolters Kluwer - Medknow 2022-06-06 /pmc/articles/PMC9241405/ /pubmed/35799534 http://dx.doi.org/10.4103/1673-5374.344829 Text en Copyright: © Neural Regeneration Research https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Research Article Liu, Xi-Lei Sun, Dong-Dong Zheng, Mu-Tian Li, Xiao-Tian Niu, Han-Hong Zhang, Lan Zhou, Zi-Wei Rong, Hong-Tao Wang, Yi Wang, Ji-Wei Yang, Gui-Li Liu, Xiao Chen, Fang-Lian Zhou, Yuan Zhang, Shu Zhang, Jian-Ning Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes |
title | Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes |
title_full | Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes |
title_fullStr | Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes |
title_full_unstemmed | Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes |
title_short | Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes |
title_sort | maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241405/ https://www.ncbi.nlm.nih.gov/pubmed/35799534 http://dx.doi.org/10.4103/1673-5374.344829 |
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