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- Murata, Y., et al.
(författare)
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Nucleus pulposus-induced apoptosis in dorsal root ganglion following experimental disc herniation in rats
- 2006
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Ingår i: Spine. - 1528-1159. ; 31:4, s. 382-90
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: The mechanisms behind the formation of a characteristic tissue reaction at the surface of the dorsal root ganglion (DRG) exposed to nucleus pulposus was studied with special reference to apoptosis using electron microscopy and immunohistochemistry in rats. OBJECTIVES: To study the mechanism of the characteristic tissue reaction at the surface of the DRG exposed to nucleus pulposus. SUMMARY OF BACKGROUND DATA: Recently, it was observed that local application of nucleus pulposus may induce a characteristic tissue reaction at the surface of the DRG. This change occurred as early as 1 day after the application of nucleus pulposus. METHODS.: Herniation of nucleus pulposus was created in the L4-L5 disc in rats. The L4 DRG were resected 3 and 24 hours after surgery. The sections of the specimens were observed using light and electron microscopy. The sections were processed for immunohistochemistry using antibodies to single-stranded DNA (ssDNA), caspase 3, and tumor necrosis factor alpha (TNF). RESULTS: There were typical changes of the cell nuclei observed by light and electron microscopy, especially those of the small-sized cells, in the DRG 24 hours after application of nucleus pulposus, indicating the presence of apoptosis. The presence of ssDNA, caspase 3, and TNF further enhanced the impression that there was apoptosis in the DRG. Nucleus pulposus induced apoptosis in the DRG at the site of application within as little as 24 hours. CONCLUSIONS: Nucleus pulposus herniated from the disc induced apoptosis in at the surface of the DRG exposed to nucleus pulpous as early as 24 hours after exposure.
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- Murata, Yasuaki, et al.
(författare)
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The role of tumor necrosis factor-alpha in apoptosis of dorsal root ganglion cells induced by herniated nucleus pulposus in rats.
- 2008
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Ingår i: Spine. - 1528-1159. ; 33:2, s. 155-62
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: The mechanisms of apoptosis underlying a characteristic tissue reaction at the surface of the dorsal root ganglion (DRG) exposed to nucleus pulposus were studied in rats with special reference to the role of tumor necrosis factor-alpha (TNF). OBJECTIVE: To study the characteristic tissue reaction at the surface of the DRG exposed to nucleus pulposus with special reference to the role of TNF. SUMMARY OF BACKGROUND DATA: Nucleus pulposus cells are capable of producing TNF. Recently, local application of nucleus pulposus was shown to induce a characteristic tissue reaction at the DRG surface due to apoptosis. METHODS: Recombinant TNF was applied to the DRG to mimic L4-L5 disc herniation in rats. The DRGs were resected 24 hours after surgery. Sections of the specimens were processed for immunohistochemistry using antisera to single-stranded DNA, Caspase 3, and TNF, and observed by light and electron microscopy. RESULTS: Typical apoptotic changes of the cell nuclei were observed in the DRG after application of TNF. The presence of single-stranded DNA, Caspase 3, and TNF further confirmed the occurrence of DRG cell apoptosis. CONCLUSION: TNF seemed to play a key role in induction of apoptosis of DRG cells, which resembled that induced by application of nucleus pulposus.
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- Olmarker, Kjell, 1958, et al.
(författare)
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Microvascular effects of chondroitinase ABC and chymopapain. An in vivo experimental study on hamsters and rabbits.
- 1990
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Ingår i: Clinical orthopaedics and related research. - 0009-921X. ; :257, s. 274-9
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Tidskriftsartikel (refereegranskat)abstract
- Immediate and long-term microvascular effects of chondroitinase ABC, 200 unit/ml, were analyzed in ten hamsters. The immediate effects on the microcirculation were studied by vital microscopy following local injection in the cheek pouch. There were no detectable effects on the microvascular blood flow during the 60 minutes of observation for chondroitinase ABC or the control. A therapeutic concentration (2000 pKat/ml) of chymopapain stopped the microcirculation in the injected area immediately, with numerous microbleedings at the border zone. Long-term effects were studied after subcutaneous injections in the ears of six rabbits. Chondroitinase ABC and the control did not cause any macroscopic or microangiographic effects. However, light microscopy showed a moderate inflammatory reaction in the subcutaneous layer for both chondroitinase ABC and the control. Chymopapain induced severe effects on the cartilage and surrounding tissues. Microangiography revealed a vessel-free zone at the injection site. Since 200 units/ml of chondroitinase ABC is four to eight times higher than the concentration that might be used for chemonucleolysis, i.e., dissolution of intervertebral discs by local enzyme injection, the present investigation suggests a wide margin of safety regarding the potential effects on blood vessels in tissues surrounding the disc.
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- Andersson, Karin, 1972, et al.
(författare)
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Inflammation in the hippocampus affects IGF1 receptor signaling and contributes to neurological sequelae in rheumatoid arthritis.
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:51
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is an inflammatory joint disease with a neurological component including depression, cognitive deficits, and pain, which substantially affect patients' quality of daily life. Insulin-like growth factor 1 receptor (IGF1R) signaling is one of the factors in RA pathogenesis as well as a known regulator of adult neurogenesis. The purpose of this study was to investigate the association between IGF1R signaling and the neurological symptoms in RA. In experimental RA, we demonstrated that arthritis induced enrichment of IBA1+ microglia in the hippocampus. This coincided with inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) and up-regulation of IGF1R in the pyramidal cell layer of the cornus ammoni and in the dentate gyrus, reproducing the molecular features of the IGF1/insulin resistance. The aberrant IGF1R signaling was associated with reduced hippocampal neurogenesis, smaller hippocampus, and increased immobility of RA mice. Inhibition of IGF1R in experimental RA led to a reduction of IRS1 inhibition and partial improvement of neurogenesis. Evaluation of physical functioning and brain imaging in RA patients revealed that enhanced functional disability is linked with smaller hippocampus volume and aberrant IGF1R/IRS1 signaling. These results point to abnormal IGF1R signaling in the brain as a mediator of neurological sequelae in RA and provide support for the potentially reversible nature of hippocampal changes.
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| 7. |
- Arai, I., et al.
(författare)
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Indomethacin blocks the nucleus pulposus-induced effects on nerve root function. An experimental study in dogs with assessment of nerve conduction and blood flow following experimental disc herniation
- 2004
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Ingår i: Eur Spine J. - : Springer Science and Business Media LLC. - 0940-6719. ; 13:8, s. 691-4
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory mechanisms have been suggested to be involved in the basic pathophysiologic events leading to nerve root injury after local application of nucleus pulposus. To assess if these nucleus pulposus-induced effects could be blocked by anti-inflammatory treatment, 41 dogs were exposed to either incision of the L6-7 disc to induce experimental disc herniation with (n=12) or without (n=14) indomethacin treatment per os (5 mg/kg per day), and no incision with (n=5) or without (n=10) indomethacin. Intraneural blood flow and nerve conduction velocity were assessed after 7 days to evaluate the degree of nerve injury. Disc incision induced a reduction in nerve root and dorsal ganglion blood flow as well as nerve function, similarly to previous studies. However, simultaneous treatment with indomethacin efficiently blocked the negative effects on both blood flow and nerve conduction but had no effects per se. The present study thus indicates that inflammatory mechanisms may be of relevance in the pathophysiology of nucleus pulposus-induced nerve root injury and thereby also for sciatica.
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| 9. |
- Brisby, Helena, 1965, et al.
(författare)
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Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica.
- 2002
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Ingår i: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. - 0940-6719. ; 11:1, s. 62-6
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Tidskriftsartikel (refereegranskat)abstract
- Proinflammatory cytokines have been identified in herniated intervertebral discs in humans, and such cytokines have experimentally been demonstrated to be important in the pathophysiological mechanisms of disc herniation. Cerebrospinal fluid (CSF) and serum concentrations of interleukin (IL)-1beta IL-6, IL-8, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were investigated using the enzyme-linked immunosorbent assay (ELISA) technique in 39 patients with lumbar disc herniation and sciatica. Pain duration and pain intensity (visual analogue scale, VAS) were recorded at inclusion, and a clinical examination was performed evaluating neurological findings. The extent of disc herniation (protrusion or extrusion/sequestration) was evaluated perioperatively. Normal concentrations of IL-1beta, IL-6, IFN-gamma and TNF-alpha were present in CSF and serum in almost all patients with lumbar disc herniation. The concentrations of IL-8 in CSF were increased in 12 out of 39 patients, and these increased levels of IL-8 correlated to a short duration of pain and to more pronounced herniation (extrusion or sequestration). No relationship between IL-8 concentrations in CSF and pain intensity, positive neurological findings or a positive straight leg-raising (SLR) test was found. The observation of increased concentrations of IL-8 in CSF in patients with a short duration of symptoms supports the concept of the initial involvement of inflammatory mechanisms after a disc herniation. The finding that most of the patients with increased concentrations of IL-8 in CSF had an extrusion or a sequestration may suggest that the increase in IL-8 is related to mechanical nerve root compression, but may also indicate a biochemical effect exerted by the herniated disc on the surrounding tissue. Further studies on the potential role of IL-8 as a biomarker for disc herniation are warranted.
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| 10. |
- Daniel, Jonsson, 1991, et al.
(författare)
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Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner.
- 2015
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Ingår i: Clinical Orthopaedics and Related Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-921X .- 1528-1132. ; 473:6, s. 1913-1919
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Tidskriftsartikel (refereegranskat)abstract
- Background During recent decades, the knowledge of the pathophysiology of disc herniation and sciatica has drastically improved. What previously was considered a strict biomechanical process is now considered a more complex interaction between leaked nucleus pulposus and the tissue in the spinal canal. An inflammatory reaction, with tumor necrosis factor (TNF) playing an essential role, has been demonstrated. However, the exact mechanisms of the pathophysiology of disc herniation remain unknown. Questions/purposes In this study we use an animal model to investigate (1) if and/or how experimental disc herniation affects gene expression in the early phase (24 hours postsurgery) in the dorsal root ganglion; and (2) if TNF inhibition can reduce any observed changes. Methods A rat model of disc herniation was used. Twenty rats were evenly divided into four groups: naïve, sham, disc herniation, and disc herniation with TNF inhibition. The dorsal root ganglion of the affected nerve root was harvested 24 hours after surgery and analyzed with a TaqMan Low Density Array® quantitative polymerase chain reaction assay. Gene expression levels in sham were compared with disc herniation to assess question 1 and disc herniation to disc herniation with TNF inhibition to assess question 2. Results Experimental disc herniation caused a decrease in the expression of the serotonin receptor 2c gene (p = 0.022). TNF inhibition was found to reduce the observed decrease in expression of serotonin receptor 2c (p = 0.037). Conclusions Our results suggest that a decrease in the expression of the serotonin receptor 2c gene may contribute to the pathophysiology of disc herniation. Further research on its involvement is warranted. Clinical Relevance This pilot study gives a brief insight into cellular changes that may contribute to the pathophysiology of disc herniation. This knowledge may contribute to the development of more and better treatment options for patients with disc herniation and sciatica.
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