title: Estrogen Attenuates Local Inflammasome Expression and Activation after Spinal Cord Injury.
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.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.|Giulan Neuroscience Research Center, Department of Anatomical Sciences, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
authors.forename: Adib
authors.initials: A
authors.lastname: Zendedel
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Mönnink
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. hassanzadeh@tums.ac.ir.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hassanzadeh
authors.affiliation: Giulan Neuroscience Research Center, Department of Anatomical Sciences, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Zaminy
authors.affiliation: Giulan Neuroscience Research Center, Department of Anatomical Sciences, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
authors.forename: Malek Masoud
authors.initials: MM
authors.lastname: Ansar
authors.affiliation: Department of Neurology, RWTH Aachen, 52074, Aachen, Germany.
authors.forename: Pardes
authors.initials: P
authors.lastname: Habib
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Slowik
authors.affiliation: Department of Anatomy II, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.|JARA-Brain, 52074, Aachen, Germany.
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology* / Q000627:therapeutic use; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018696:Neuroprotective Agents; C573346:Nlrp3 protein, rat; D004958:Estradiol
keywords: Estrogen; Inflammasome; Spinal cord injury