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The expressions of NLRP1, NLRP3, and AIM2 inflammasome complexes in the contusive spinal cord injury rat model and their responses to hormonal therapy

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Abstract

Spinal cord injury (SCI) is a devastating condition with a growing incidence in developing countries. The activity of inflammasome complexes initiates neuroinflammation, which is a key player in SCI pathogenesis. Here, NLRP1, NLRP3, and absent in melanoma 2 (AIM2) inflammasome complexes were assessed in the contusive (T6) SCI rats for their expression profiles and their response to hormonal therapy (10 mg/kg melatonin or 25 μg/kg 17β-estradiol [E2] every 12 h until 72 h). Two phases was considered in this study: the dominant time of inflammasome activation, which was 72 h post-SCI and the response from each complex to hormonal therapy at this time. Gene and protein expressions of NLRP1, NLRP3, AIM2, ASC, and caspase-1 were evaluated by real-time PCR (for gene analysis), western blot, and immunohistochemistry (IHC), and biochemical presence of IL-18 and IL-1β in spinal cord tissue homogenates was analyzed by enzyme-linked immunosorbent assay (ELISA). The whole inflammasome complexes showed high expressions in the SCI group, while after hormonal therapy, these alterations were counteracted, which were more conspicuous for the NLRP1 and NLRP3. Melatonin had no predilection over E2 for such effect. Finally, the expression profile of signaling related to the synthesis (TLR4/NF-κB) and activation (NADPH oxidase 2 [NOX2]/TXNIP) of inflammasome complexes was surveyed, and there were low activities for the two pathways in SCI rats that underwent hormone therapy. From the findings, it is concluded that both melatonin and E2 are efficient to target inflammasome activation in the SCI rats.

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Funding

The thesis was designed by a combination work between Iran University of Medical Sciences (major: grant number 98-2-4-14010) and Kurdistan University of Medical Sciences (IR.MUK.REC.1397/365 and IR.MUK.REC.1397/366).

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Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Jamal Majidpoor, Fatemeh Moradi, Reza Shirazi & Mohammad Taghi Joghataei

  2. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Jamal Majidpoor, Fatemeh Moradi, Reza Shirazi & Mohammad Taghi Joghataei

  3. Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Zahra Khezri, Parsa Rostamzadeh, Keywan Mortezaee, Mohammad Jafar Rezaie, Fardin Fathi & Morteza Abouzaripour

  4. Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Keywan Mortezaee

  5. Department of Operating Room, School of Para-Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Mehdi Ghasemzadeh Bariki

  6. Department of Neurosciences, Faculty of Advance Technology in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mohammad Taghi Joghataei

Authors
  1. Jamal Majidpoor
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  2. Zahra Khezri
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  7. Morteza Abouzaripour
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  11. Mohammad Taghi Joghataei
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Correspondence to Keywan Mortezaee, Fatemeh Moradi, Reza Shirazi or Mohammad Taghi Joghataei.

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The authors declare that they have no conflict of interest.

Ethical approval

All animal-related procedures, including anesthesia and surgery, were carried out according to the national and institutional guidelines of Iran University of Medical Science for use and care of animals in the laboratory (ethical approval code IR.IUMS.FMD.REC.1398.287).

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Majidpoor, J., Khezri, Z., Rostamzadeh, P. et al. The expressions of NLRP1, NLRP3, and AIM2 inflammasome complexes in the contusive spinal cord injury rat model and their responses to hormonal therapy. Cell Tissue Res 381, 397–410 (2020). https://doi.org/10.1007/s00441-020-03250-5

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  • DOI: https://doi.org/10.1007/s00441-020-03250-5

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