Role of Toll like receptor 4 signaling pathway in the secondary damage induced by experimental spinal cord injury
Abstract
Toll-like receptors (TLRs) are signaling receptors in the innate immune system that is specific immunologic response to systemic bacterial infection and injury. TLRs contribute to the initial induction of neuroinflammation in the CNS. In spinal cord injury (SCI) intricate immune cell interactions are triggered, typically consisting of a staggered multiphasic immune cell response, which can become deregulated. The present study aims to evaluate the role of TLR4 signaling pathway in the development of secondary damage in a mouse model of SCI using TLR4-deficient (TLR4-KO) mice such as C57BL/10ScNJ and C3H/HeJ mice. We evaluated behavioral changes, histological, immunohistochemistry and molecular assessment in TLR4-KO after SCI. SCI was performed on TLR4-KO and wild-type (WT) mice by the application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy. Mice were sacrificed at 24h after SCI to evaluate the various parameters. SCI TLR4 KO mice developed severer hind limb motor dysfunction and neuronal death by histological evaluation, myeloid differentiation primary response 88 (Myd88) expression as well as an increase in nuclear factor NF-κB activity, tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels, glial fibrillary acidic protein (GFAP), microglia marker (CD11β), inducible nitric oxide synthases (iNOS), poly-ADP-ribose polymerase (PARP) and nitrotyrosine expression compared to WT mice. Moreover, the absence of TLR4 also caused a decrease i…
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In the brain, under sterile inflammatory conditions, there are increasing reports showing activation of the Type I IFN response in ischemia, spinal cord injury, and in two different AD mouse models as well as in AD patients.
“However, in the brain, and under sterile inflammatory conditions, there are increasing numbers of reports showing activation of the Type I IFN response in ischemia (McDonough et al., 2017), spinal cord injury (Impellizzeri et al., 2015) and in two different AD mouse models, the 5xFAD (Landel et al., 2014) and APP/PS1 (Taylor et al., 2014), as well as in AD patients (Taylor et al., 2014).”
From TET2 Regulates the Neuroinflammatory Response in Microglia (2019) · cites this paper as Impellizzeri et al., 2015
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References 45 · Cited by 58
- Authors
- Impellizzeri, D., Ahmad, A., Di Paola, R., Campolo, M., Navarra, M., Esposito, E., & Cuzzocrea, S.
- Affiliations
- University of Messina (IT)
- Corresponding author
- Cuzzocrea, Salvatore
- ORCID
- Venue
- Immunobiology
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 220
- Issue
- 9
- Pages
- 1039-1049
- ISSN
- 0171-2985 (ISSN-L)
- OpenAlex
- W326052928
- Cited by
- 58
- References
- 45
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 2 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 3
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Università degli Studi di Messina
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TLR4, spinal cord injury, secondary injury, neuroinflammation, MyD88, NF-κB, TNF-α, IL-1β, interferon-beta, IRF3, nitrotyrosine, inducible nitric oxide synthase, Bax/Bcl-2 ratio, microglia, TLR4-deficient mice, motor impairment, neuronal cell death
- MeSH terms
- Animals, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Hindlimb, Inflammation, Mice, Inbred C3H, Mice, Inbred C57BL, Nerve Tissue Proteins, Poly(ADP-ribose) Polymerases, Spinal Cord Injuries, Tumor Necrosis Factor-alpha, Neuroimmunomodulation, Signal Transduction, Interferon-beta, Apoptosis, Mice, Knockout, Neutrophil Infiltration, CD11b Antigen, Interferon Regulatory Factor-3, bcl-2-Associated X Protein, Toll-Like Receptor 4, Mice, Transcription Factor RelA, Nitric Oxide Synthase Type II, Interleukin-1beta, Myeloid Differentiation Factor 88
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