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Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats
Acute ischemic stroke (AIS) is a devastating neurological condition with a lack of neuroprotective therapeutic options, despite the reperfusion modalities thrombolysis and thrombectomy. Post-ischemic brain damage is aggravated by an excessive inflammatory cascade involving the activation and regulat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370209/ https://www.ncbi.nlm.nih.gov/pubmed/32645874 http://dx.doi.org/10.3390/ijms21134795 |
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author | Habib, Pardes Harms, Julie Zendedel, Adib Beyer, Cordian Slowik, Alexander |
author_facet | Habib, Pardes Harms, Julie Zendedel, Adib Beyer, Cordian Slowik, Alexander |
author_sort | Habib, Pardes |
collection | PubMed |
description | Acute ischemic stroke (AIS) is a devastating neurological condition with a lack of neuroprotective therapeutic options, despite the reperfusion modalities thrombolysis and thrombectomy. Post-ischemic brain damage is aggravated by an excessive inflammatory cascade involving the activation and regulation of the pro-inflammatory cytokines IL-1β and IL-18 by inflammasomes. However, the role of AIM2 and NLRC4 inflammasomes and the influence of the neuroprotective steroids 17β-estradiol (E2) and progesterone (P) on their regulation after ischemic stroke have not yet been conclusively elucidated. To address the latter, we subjected a total of 65 rats to 1 h of transient Middle Cerebral Artery occlusion (tMCAO) followed by a reperfusion period of 72 h. Moreover, we evaluated the expression and regulation of AIM2 and NLRC4 in glial single-cell cultures (astroglia and microglia) after oxygen–glucose deprivation (OGD). The administration of E2 and P decreased both infarct sizes and neurological impairments after cerebral ischemia in rats. We detected a time-dependent elevation of gene and protein levels (Western Blot/immunohistochemistry) of the AIM2 and NLRC4 inflammasomes in the post-ischemic brains. E2 or P selectively mitigated the stroke-induced increase of AIM2 and NLRC4. While both inflammasomes seemed to be exclusively abundant in neurons under physiological and ischemic conditions in vivo, single-cell cultures of cortical astrocytes and microglia equally expressed both inflammasomes. In line with the in vivo data, E and P selectively reduced AIM2 and NLRC4 in primary cortical astrocytes and microglial cells after OGD. In conclusion, the post-ischemic elevation of AIM2 and NLRC4 and their down-regulation by E2 and P may shed more light on the anti-inflammatory effects of both gonadal hormones after stroke. |
format | Online Article Text |
id | pubmed-7370209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73702092020-07-21 Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats Habib, Pardes Harms, Julie Zendedel, Adib Beyer, Cordian Slowik, Alexander Int J Mol Sci Article Acute ischemic stroke (AIS) is a devastating neurological condition with a lack of neuroprotective therapeutic options, despite the reperfusion modalities thrombolysis and thrombectomy. Post-ischemic brain damage is aggravated by an excessive inflammatory cascade involving the activation and regulation of the pro-inflammatory cytokines IL-1β and IL-18 by inflammasomes. However, the role of AIM2 and NLRC4 inflammasomes and the influence of the neuroprotective steroids 17β-estradiol (E2) and progesterone (P) on their regulation after ischemic stroke have not yet been conclusively elucidated. To address the latter, we subjected a total of 65 rats to 1 h of transient Middle Cerebral Artery occlusion (tMCAO) followed by a reperfusion period of 72 h. Moreover, we evaluated the expression and regulation of AIM2 and NLRC4 in glial single-cell cultures (astroglia and microglia) after oxygen–glucose deprivation (OGD). The administration of E2 and P decreased both infarct sizes and neurological impairments after cerebral ischemia in rats. We detected a time-dependent elevation of gene and protein levels (Western Blot/immunohistochemistry) of the AIM2 and NLRC4 inflammasomes in the post-ischemic brains. E2 or P selectively mitigated the stroke-induced increase of AIM2 and NLRC4. While both inflammasomes seemed to be exclusively abundant in neurons under physiological and ischemic conditions in vivo, single-cell cultures of cortical astrocytes and microglia equally expressed both inflammasomes. In line with the in vivo data, E and P selectively reduced AIM2 and NLRC4 in primary cortical astrocytes and microglial cells after OGD. In conclusion, the post-ischemic elevation of AIM2 and NLRC4 and their down-regulation by E2 and P may shed more light on the anti-inflammatory effects of both gonadal hormones after stroke. MDPI 2020-07-07 /pmc/articles/PMC7370209/ /pubmed/32645874 http://dx.doi.org/10.3390/ijms21134795 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Habib, Pardes Harms, Julie Zendedel, Adib Beyer, Cordian Slowik, Alexander Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats |
title | Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats |
title_full | Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats |
title_fullStr | Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats |
title_full_unstemmed | Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats |
title_short | Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats |
title_sort | gonadal hormones e2 and p mitigate cerebral ischemia-induced upregulation of the aim2 and nlrc4 inflammasomes in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370209/ https://www.ncbi.nlm.nih.gov/pubmed/32645874 http://dx.doi.org/10.3390/ijms21134795 |
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