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Estrogen Attenuates Local Inflammasome Expression and Activation after Spinal Cord Injury

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Abstract

17-estradiol (E2) is a neuroprotective hormone with a high anti-inflammatory potential in different neurological disorders. The inflammatory response initiated by spinal cord injury (SCI) involves the processing of interleukin-1beta (IL-1b) and IL-18 mediated by caspase-1 which is under the control of an intracellular multiprotein complex called inflammasome. We recently described in a SCI model that between 24 and 72 h post-injury, most of inflammasome components including IL-18, IL-1b, NLRP3, ASC, and caspase-1 are upregulated. In this study, we investigated the influence of E2 treatment after spinal cord contusion on inflammasome regulation. After contusion of T9 spinal segment, 12-week-old male Wistar rats were treated subcutaneously with E2 immediately after injury and every 12 h for the next 3 days. Behavioral scores were significantly improved in E2-treated animals compared to vehicle-treated groups. Functional improvement in E2-treated animals was paralleled by the attenuated expression of certain inflammasome components such as ASC, NLRP1b, and NLRP3 together with IL1b, IL-18, and caspase-1. On the histopathological level, microgliosis and oligodendrocyte injury was ameliorated. These findings support and extend the knowledge of the E2-mediated neuroprotective function during SCI. The control of the inflammasome machinery by E2 might be a missing piece of the puzzle to understand the anti-inflammatory potency of E2.

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Acknowledgements

This work was supported by two internal grants from the Medical Clinic of the RWTH Aachen University START (A.Z. and A.S.). We appreciate the discussions with and advice from Prof. J. Bernhagen, formerly head of the Institute of Biochemistry at the RWTH Aachen University.

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Correspondence to Gholamreza Hassanzadeh.

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Research and animal care procedures were approved by the Review Board for the Care of Animal Subjects of the district government (Tehran, Iran).

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Adib Zendedel and Fabian Mönnink contributed equally

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Zendedel, A., Mönnink, F., Hassanzadeh, G. et al. Estrogen Attenuates Local Inflammasome Expression and Activation after Spinal Cord Injury. Mol Neurobiol 55, 1364–1375 (2018). https://doi.org/10.1007/s12035-017-0400-2

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