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Infliximab attenuates immunoreactivity of brain-derived neurotrophic factor in a rat model of herniated nucleus pulposus

Artikel i vetenskaplig tidskrift
Författare A. Onda
Y. Murata
Björn Rydevik
Karin Larsson
S. Kikuchi
Kjell Olmarker
Publicerad i Spine
Volym 29
Nummer/häfte 17
Sidor 1857-61
ISSN 1528-1159 (Electronic)
Publiceringsår 2004
Publicerad vid Institutionen för de kirurgiska disciplinerna, Avdelningen för ortopedi
Sidor 1857-61
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Administration, Topical, Animals, Antibodies, Monoclonal/administration & dosage/pharmacology/*therapeutic, use, Brain-Derived Neurotrophic Factor/*biosynthesis, Drug Administration Schedule, Drug Evaluation, Preclinical, Female, Ganglia, Spinal/chemistry/pathology, Gene Expression Regulation/*drug effects, Intervertebral Disk Displacement/complications/*drug therapy/metabolism, Neurons/chemistry, Posterior Horn Cells/chemistry/pathology, Rats, Rats, Sprague-Dawley, Sciatica/*drug therapy/etiology/metabolism, Spinal Cord/chemistry/pathology, Spinal Nerve Roots
Ämneskategorier Ortopedi

Sammanfattning

STUDY DESIGN: The effect of infliximab, a chimeric monoclonal antibody to TNF-alpha, on induction of brain-derived neurotrophic factor (BDNF) was examined using an experimental herniated nucleus pulposus (NP) model. OBJECTIVES: To investigate whether treatment of infliximab could attenuate an induction of BDNF, which functions as a modulator of pain, following NP application to the nerve root. SUMMARY OF BACKGROUND DATA: Evidence from basic scientific studies proposes that TNF-alpha is involved in the development of NP-induced nerve injuries. However, the therapeutic mechanisms of infliximab against pain have not been elucidated experimentally. METHODS: Twenty rats were used in this study. In the test groups, the animals underwent application of NP to the L4 nerve roots and received a single systemic (intraperitoneal) injection of infliximab at the time of surgery (Infli-0 group, n = 5) or at 1 day after operation (Infli-1 group, n = 5). As a control treatment, sterile water was administered intraperitoneally to 5 rats with NP application (NP group) and to 5 sham-operated rats (sham group). On day 3 after surgery, the L4 dorsal root ganglion (DRG) and L4 spinal segment were harvested and assessed regarding BDNF immunoreactivity. RESULTS.: Application of NP induced a marked increase of BDNF immunoreactivity in number in the DRG neurons and within the superficial layer in the dorsal horn compared with the sham group (P < 0.01). Infliximab treatment in the Infli-0 and Infli-1 groups reduced the BDNF induction in both DRG and spinal cord (P < 0.05). CONCLUSION: These findings indicate that infliximab attenuates the elevated BDNF levels induced by NP. The present study therefore further indicates the importance of TNF-alpha in sciatica due to disc herniation and the possible therapeutic use of a TNF-alpha inhibitor for this condition.

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