Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice

Autor: Kate Lykke Lambertsen, Lujitha Suntharalingam, Minna Christiansen Lund, Åsa Fex Svenningsen, Bettina Hjelm Clausen, Roberta Brambilla, Louise Helskov Jørgensen, Ditte Gry Ellman, Simon Bertram Flæng, Matilda Degn, Hans Gram Novrup
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Monocytes/cytology
0301 basic medicine
Monocytes
Mice
0302 clinical medicine
Medicine
Epidural administration
Spinal cord injury
Genes
Dominant
Microglia
Homozygote
Cytokines/metabolism
Glial Fibrillary Acidic Protein/metabolism
Spinal Cord Injuries/blood
Treatment Outcome
medicine.anatomical_structure
Cytokines
Female
medicine.symptom
Research Article
lcsh:RB1-214
Tumor Necrosis Factor-alpha/blood
medicine.medical_specialty
Cord
Genotype
Article Subject
Immunology
CCL2
Proinflammatory cytokine
Lesion
03 medical and health sciences
Internal medicine
Glial Fibrillary Acidic Protein
lcsh:Pathology
Animals
Maze Learning
Spinal Cord Injuries
Inflammation
Tumor Necrosis Factor-alpha
business.industry
Macrophages
Cell Membrane/metabolism
Cell Membrane
Macrophages/cytology
Cell Biology
medicine.disease
Spinal cord
030104 developmental biology
Endocrinology
business
030217 neurology & neurosurgery
Zdroj: Mediators of Inflammation, Vol 2016 (2016)
Ellman, D G, Degn, M, Lund, M C, Clausen, B H, Novrup, H G, Flæng, S B, Jørgensen, L H, Suntharalingam, L, Fex Svenningsen, Å, Brambilla, R & Lambertsen, K L 2016, ' Genetic ablation of soluble TNF does not affect lesion size and functional recovery after moderate spinal cord injury in mice ', Mediators of Inflammation, vol. 2016, 2684098 . https://doi.org/10.1155/2016/2684098
Mediators of Inflammation
ISSN: 1466-1861
0962-9351
DOI: 10.1155/2016/2684098
Popis: Traumatic spinal cord injury (SCI) is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF) within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF) and as cleaved soluble TNF (solTNF). We previously demonstrated that epidural administration of a dominant-negative inhibitor of solTNF, XPro1595, to the contused spinal cord resulted in changes in Iba1 protein expression in microglia/macrophages, decreased lesion volume, and improved locomotor function. Here, we extend our studies using mice expressing mTNF, but no solTNF (mTNFΔ/Δ), to study the effect of genetic ablation of solTNF on SCI. We demonstrate that TNF levels were significantly decreased within the lesioned spinal cord 3 days after SCI inmTNFΔ/Δmice compared to littermates. This decrease did, however, not translate into significant changes in other pro- and anti-inflammatory cytokines (IL-10, IL-1β, IL-6, IL-5, IL-2, CXCL1, CCL2, or CCL5), despite a tendency towards increased IL-10 and decreased IL-1β, TNFR1, and TNFR2 levels inmTNFΔ/Δmice. In addition, microglial and leukocyte infiltration, activation state (Iba1, CD11b, CD11c, CD45, and MHCII), lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI.
Databáze: OpenAIRE
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