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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Published: |
Multidisciplinary Digital Publishing Institute
2022
|
| _version_ | 1825938684389621760 |
|---|---|
| author | Che Mohd Nassir, Che Mohd Nasril Zolkefley, Mohd K. I. Ramli, Muhammad Danial Norman, Haziq Hazman Abdul Hamid, Hafizah Mustapha, Muzaimi |
| 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 |
| collection | UPM |
| 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. |
| first_indexed | 2024-03-06T11:17:07Z |
| format | Article |
| id | upm.eprints-102299 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2024-03-06T11:17:07Z |
| publishDate | 2022 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | 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 |
| 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 |
| 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_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_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_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 |
| work_keys_str_mv | AT chemohdnassirchemohdnasril neuroinflammationandcovid19ischemicstrokerecoveryevolvingevidenceforthemediatingrolesoface2angiotensin1a7masreceptoraxisandnlrp3inflammasome AT zolkefleymohdki neuroinflammationandcovid19ischemicstrokerecoveryevolvingevidenceforthemediatingrolesoface2angiotensin1a7masreceptoraxisandnlrp3inflammasome AT ramlimuhammaddanial neuroinflammationandcovid19ischemicstrokerecoveryevolvingevidenceforthemediatingrolesoface2angiotensin1a7masreceptoraxisandnlrp3inflammasome AT normanhaziqhazman neuroinflammationandcovid19ischemicstrokerecoveryevolvingevidenceforthemediatingrolesoface2angiotensin1a7masreceptoraxisandnlrp3inflammasome AT abdulhamidhafizah neuroinflammationandcovid19ischemicstrokerecoveryevolvingevidenceforthemediatingrolesoface2angiotensin1a7masreceptoraxisandnlrp3inflammasome AT mustaphamuzaimi neuroinflammationandcovid19ischemicstrokerecoveryevolvingevidenceforthemediatingrolesoface2angiotensin1a7masreceptoraxisandnlrp3inflammasome |