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Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome

Cerebrovascular events, notably acute ischemic strokes (AIS), have been reported in the setting of novel coronavirus disease (COVID-19) infection. Commonly regarded as cryptogenic, to date, the etiology is thought to be multifactorial and remains obscure; it is linked either to a direct viral invasi...

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Main Authors: Che Mohd Nassir, Che Mohd Nasril, Zolkefley, Mohd K. I., Ramli, Muhammad Danial, Norman, Haziq Hazman, Abdul Hamid, Hafizah, Mustapha, Muzaimi
Format: Article
Published: Multidisciplinary Digital Publishing Institute 2022
Online Access:http://psasir.upm.edu.my/id/eprint/102299/
https://www.mdpi.com/1422-0067/23/6/3085
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spelling my.upm.eprints.1022992023-06-16T04:05:19Z http://psasir.upm.edu.my/id/eprint/102299/ Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome Che Mohd Nassir, Che Mohd Nasril Zolkefley, Mohd K. I. Ramli, Muhammad Danial Norman, Haziq Hazman Abdul Hamid, Hafizah Mustapha, Muzaimi Cerebrovascular events, notably acute ischemic strokes (AIS), have been reported in the setting of novel coronavirus disease (COVID-19) infection. Commonly regarded as cryptogenic, to date, the etiology is thought to be multifactorial and remains obscure; it is linked either to a direct viral invasion or to an indirect virus-induced prothrombotic state, with or without the presence of conventional cerebrovascular risk factors. In addition, patients are at a greater risk of developing long-term negative sequelae, i.e., long-COVID-related neurological problems, when compared to non-COVID-19 stroke patients. Central to the underlying neurobiology of stroke recovery in the context of COVID-19 infection is reduced angiotensin-converting enzyme 2 (ACE2) expression, which is known to lead to thrombo-inflammation and ACE2/angiotensin-(1–7)/mitochondrial assembly receptor (MasR) (ACE2/Ang-(1-7)/MasR) axis inhibition. Moreover, after AIS, the activated nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome may heighten the production of numerous proinflammatory cytokines, mediating neuro-glial cell dysfunction, ultimately leading to nerve-cell death. Therefore, potential neuroprotective therapies targeting the molecular mechanisms of the aforementioned mediators may help to inform rehabilitation strategies to improve brain reorganization (i.e., neuro-gliogenesis and synaptogenesis) and secondary prevention among AIS patients with or without COVID-19. Therefore, this narrative review aims to evaluate the mediating role of the ACE2/Ang- (1-7)/MasR axis and NLRP3 inflammasome in COVID-19-mediated AIS, as well as the prospects of these neuroinflammation mediators for brain repair and in secondary prevention strategies against AIS in stroke rehabilitation. Multidisciplinary Digital Publishing Institute 2022-03-13 Article PeerReviewed Che Mohd Nassir, Che Mohd Nasril and Zolkefley, Mohd K. I. and Ramli, Muhammad Danial and Norman, Haziq Hazman and Abdul Hamid, Hafizah and Mustapha, Muzaimi (2022) Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome. International Journal of Molecular Sciences, 23 (6). art. no. 3085. pp. 1-23. ISSN 1661-6596; ESSN: 1422-0067 https://www.mdpi.com/1422-0067/23/6/3085 10.3390/ijms23063085
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
description Cerebrovascular events, notably acute ischemic strokes (AIS), have been reported in the setting of novel coronavirus disease (COVID-19) infection. Commonly regarded as cryptogenic, to date, the etiology is thought to be multifactorial and remains obscure; it is linked either to a direct viral invasion or to an indirect virus-induced prothrombotic state, with or without the presence of conventional cerebrovascular risk factors. In addition, patients are at a greater risk of developing long-term negative sequelae, i.e., long-COVID-related neurological problems, when compared to non-COVID-19 stroke patients. Central to the underlying neurobiology of stroke recovery in the context of COVID-19 infection is reduced angiotensin-converting enzyme 2 (ACE2) expression, which is known to lead to thrombo-inflammation and ACE2/angiotensin-(1–7)/mitochondrial assembly receptor (MasR) (ACE2/Ang-(1-7)/MasR) axis inhibition. Moreover, after AIS, the activated nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome may heighten the production of numerous proinflammatory cytokines, mediating neuro-glial cell dysfunction, ultimately leading to nerve-cell death. Therefore, potential neuroprotective therapies targeting the molecular mechanisms of the aforementioned mediators may help to inform rehabilitation strategies to improve brain reorganization (i.e., neuro-gliogenesis and synaptogenesis) and secondary prevention among AIS patients with or without COVID-19. Therefore, this narrative review aims to evaluate the mediating role of the ACE2/Ang- (1-7)/MasR axis and NLRP3 inflammasome in COVID-19-mediated AIS, as well as the prospects of these neuroinflammation mediators for brain repair and in secondary prevention strategies against AIS in stroke rehabilitation.
format Article
author Che Mohd Nassir, Che Mohd Nasril
Zolkefley, Mohd K. I.
Ramli, Muhammad Danial
Norman, Haziq Hazman
Abdul Hamid, Hafizah
Mustapha, Muzaimi
spellingShingle Che Mohd Nassir, Che Mohd Nasril
Zolkefley, Mohd K. I.
Ramli, Muhammad Danial
Norman, Haziq Hazman
Abdul Hamid, Hafizah
Mustapha, Muzaimi
Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome
author_facet Che Mohd Nassir, Che Mohd Nasril
Zolkefley, Mohd K. I.
Ramli, Muhammad Danial
Norman, Haziq Hazman
Abdul Hamid, Hafizah
Mustapha, Muzaimi
author_sort Che Mohd Nassir, Che Mohd Nasril
title Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome
title_short Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome
title_full Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome
title_fullStr Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome
title_full_unstemmed Neuroinflammation and COVID-19 ischemic stroke recovery —evolving evidence for the mediating roles of ACE2/angiotensin-1a“7/Mas receptor axis and NLRP3 inflammasome
title_sort neuroinflammation and covid-19 ischemic stroke recovery —evolving evidence for the mediating roles of ace2/angiotensin-1a“7/mas receptor axis and nlrp3 inflammasome
publisher Multidisciplinary Digital Publishing Institute
publishDate 2022
url http://psasir.upm.edu.my/id/eprint/102299/
https://www.mdpi.com/1422-0067/23/6/3085
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score 13.211869

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