title: Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model.
abstract: Stromal cell-derived factor-1 alpha (SDF-1a) or CXCL12 is an important cytokine with multiple functions in the brain during development and in adulthood. The inflammatory response initiated by spinal cord injury (SCI) involves the processing of interleukin-1beta (IL-1ß) and IL-18 mediated by caspase-1 which is under the control of an intracellular multiprotein complex termed inflammasome. Using an SCI rat model, we found improved functional long-term recovery which is paralleled by a reduction of apoptosis after intrathecal treatment with SDF-1a. An intriguing aspect is that SDF-1a changed the number of neuroinflammatory cells in the damaged area. We further examined the cellular localization and sequential expression of several inflammasomes during SCI at 6 h, 24 h, 3 days, and 7 days as well as the role of SDF-1a as a regulatory factor for inflammasomes. Using 14-week old male Wistar rats, spinal cord contusion was applied at the thoracic segment 9, and animals were subsequently treated with SDF-1a via intrathecal application through an osmotic pump. SCI temporally increased the expression of the inflammasomes NLRP3, ASC, the inflammatory marker tumor necrosis factor-a (TNF-a), interleukin-1ß (IL-1β) and IL-18. SDF-1a significantly reduced the levels of IL-18, IL-1b, TNF-a, NLRP3, ASC, and caspase-1. Immunofluorescence double-labeling demonstrated that microglia and neurons are major sources of the ASC and NLRP3 respectivley. Our data provide clear evidence that SCI stimulates a complex scenario of inflammasome activation at the injured site and that SDF-1a-mediated neuroprotection presumably depends on the attenuation of the inflammasome complex.
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074, Aachen, Germany. azendedel@ukaachen.de.|Department of Anatomical Sciences, Faculty of Medicine, Gilan University of Medical Sciences, Rasht, Iran. azendedel@ukaachen.de.
authors.forename: Adib
authors.initials: A
authors.lastname: Zendedel
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Johann
authors.affiliation: School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Soraya
authors.initials: S
authors.lastname: Mehrabi
authors.affiliation: Department of Anatomy and Neuroscience, Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad-Taghi
authors.initials: MT
authors.lastname: Joghataei
authors.affiliation: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hassanzadeh
authors.affiliation: Institute of Neuroanatomy, RWTH Aachen University, 52074, Aachen, Germany.|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, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism; D002452:Cell Count; D054377:Chemokine CXCL12 / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000150:complications / Q000473:pathology; D058847:Inflammasomes / Q000378:metabolism*; D007278:Injections, Spinal; D008124:Locomotion / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D053468:CARD Signaling Adaptor Proteins; D054377:Chemokine CXCL12; D005904:Glial Fibrillary Acidic Protein; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C498535:Pycard protein, rat; D012333:RNA, Messenger
keywords: Astroglia; Inflammasome; Microglia; SDF-1a (CXCL12); Spinal cord injury