Neuroinflammation and COVID-19 ischemic stroke recovery—Evolving evidence for the mediating roles of the ACE2/angiotensin-(1–7)/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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI
2022
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| Subjects: | |
| Online Access: | http://umpir.ump.edu.my/id/eprint/35138/ http://umpir.ump.edu.my/id/eprint/35138/1/Neuroinflammation%20and%20COVID-19%20ischemic%20stroke%20recovery_evolving%20evidence%20for%20the%20mediating%20roles%20of%20the%20ace2_angiotensin-%281%E2%80%937%29.pdf |
| Summary: | 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. |
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