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TNF-alpha blockage in a mouse model of SCI: evidence for improved outcome.
Shock. 2008 Jan; 29(1):32-41.S

Abstract

The aim of our study was to evaluate in vivo the therapeutic efficacy of genetic inhibition of TNF-alpha using TNF-R1 knockout mice in an experimental model of spinal cord trauma. Spinal cord injury was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. To elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-alpha, we also investigated the effect of infliximab, a TNF-alpha-soluble receptor construct, on spinal cord damage. Pharmacological and genetic TNF-alpha inhibition significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (evaluated by myeloperoxidase activity), (3) cytokine expression (TNF-alpha), (4) and apoptosis (terminal deoxynucleotidyltransferase-mediated uridine triphosphate end labeling staining, Bax, Bcl-2, and Fas-L expression). In a separate set of experiments, we have also demonstrated that TNF-alpha inhibition significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that inhibition of TNF-alpha reduces the development of inflammation and tissue injury associated with spinal cord trauma, suggesting a possible role of TNF-alpha on the pathogenesis of spinal cord injury.

Authors+Show Affiliations

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17621255

Citation

Genovese, Tiziana, et al. "TNF-alpha Blockage in a Mouse Model of SCI: Evidence for Improved Outcome." Shock (Augusta, Ga.), vol. 29, no. 1, 2008, pp. 32-41.
Genovese T, Mazzon E, Crisafulli C, et al. TNF-alpha blockage in a mouse model of SCI: evidence for improved outcome. Shock. 2008;29(1):32-41.
Genovese, T., Mazzon, E., Crisafulli, C., Di Paola, R., Muià, C., Esposito, E., Bramanti, P., & Cuzzocrea, S. (2008). TNF-alpha blockage in a mouse model of SCI: evidence for improved outcome. Shock (Augusta, Ga.), 29(1), 32-41.
Genovese T, et al. TNF-alpha Blockage in a Mouse Model of SCI: Evidence for Improved Outcome. Shock. 2008;29(1):32-41. PubMed PMID: 17621255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF-alpha blockage in a mouse model of SCI: evidence for improved outcome. AU - Genovese,Tiziana, AU - Mazzon,Emanuela, AU - Crisafulli,Concetta, AU - Di Paola,Rosanna, AU - Muià,Carmelo, AU - Esposito,Emanuela, AU - Bramanti,Placido, AU - Cuzzocrea,Salvatore, PY - 2007/7/11/pubmed PY - 2008/3/1/medline PY - 2007/7/11/entrez SP - 32 EP - 41 JF - Shock (Augusta, Ga.) JO - Shock VL - 29 IS - 1 N2 - The aim of our study was to evaluate in vivo the therapeutic efficacy of genetic inhibition of TNF-alpha using TNF-R1 knockout mice in an experimental model of spinal cord trauma. Spinal cord injury was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. To elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-alpha, we also investigated the effect of infliximab, a TNF-alpha-soluble receptor construct, on spinal cord damage. Pharmacological and genetic TNF-alpha inhibition significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (evaluated by myeloperoxidase activity), (3) cytokine expression (TNF-alpha), (4) and apoptosis (terminal deoxynucleotidyltransferase-mediated uridine triphosphate end labeling staining, Bax, Bcl-2, and Fas-L expression). In a separate set of experiments, we have also demonstrated that TNF-alpha inhibition significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that inhibition of TNF-alpha reduces the development of inflammation and tissue injury associated with spinal cord trauma, suggesting a possible role of TNF-alpha on the pathogenesis of spinal cord injury. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/17621255/TNF_alpha_blockage_in_a_mouse_model_of_SCI:_evidence_for_improved_outcome_ L2 - https://doi.org/10.1097/shk.0b013e318059053a DB - PRIME DP - Unbound Medicine ER -