Next Article in Journal
Integrative Analyses of Widely Targeted Metabolic Profiling and Transcriptome Data Reveals Molecular Insight into Metabolomic Variations during Apple (Malus domestica) Fruit Development and Ripening
Next Article in Special Issue
Galectin-3 in Inflammasome Activation and Primary Biliary Cholangitis Development
Previous Article in Journal
Transcriptomic Profile of Primary Culture of Skeletal Muscle Cells Isolated from Semitendinosus Muscle of Beef and Dairy Bulls
Previous Article in Special Issue
The NLRP1 Inflammasome in Human Skin and Beyond
Open AccessArticle

Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats

1
Department of Neurology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
2
Institute of Biochemistry and Molecular Immunology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
3
Institute of Neuroanatomy, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
4
JARA Brain, RWTH Aachen University, 52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4795; https://doi.org/10.3390/ijms21134795
Received: 15 June 2020 / Revised: 1 July 2020 / Accepted: 3 July 2020 / Published: 7 July 2020
(This article belongs to the Special Issue Inflammasome)
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. View Full-Text
Keywords: Stroke; Inflammasomes; AIM; NLRC4; Estrogen; Progesterone; Neuroprotection; Microglia; Astrocytes; OGD Stroke; Inflammasomes; AIM; NLRC4; Estrogen; Progesterone; Neuroprotection; Microglia; Astrocytes; OGD
Show Figures

Figure 1

MDPI and ACS Style

Habib, P.; Harms, J.; Zendedel, A.; Beyer, C.; Slowik, A. Gonadal Hormones E2 and P Mitigate Cerebral Ischemia-Induced Upregulation of the AIM2 and NLRC4 Inflammasomes in Rats. Int. J. Mol. Sci. 2020, 21, 4795.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop