| 1. |
- Brisby, Helena, 1965, et al.
(författare)
-
Cell therapy for disc degeneration--potentials and pitfalls
- 2004
-
Ingår i: Orthop Clin North Am. - 0030-5898. ; 35:1, s. 85-93
-
Tidskriftsartikel (refereegranskat)abstract
- Disc degeneration is considered a major source of pain in patients with chronic low back pain. Novel strategies to cure or decrease the symptoms and increase the patient's quality of life and function are under development. Until recently conservative treatment and fusion surgery were the main therapeutic options. Disc prostheses are undergoing clinical evaluation. The potential for cell transplantation to the intervertebral disc with mature autologous disc cells, chondrocytes, or stem cells is in early stages of investigation. Cell transplantation potentially can increase proteoglycan production and induce disc regeneration or slow down the degeneration process. In animal models, transplantation of autologous disc cells and chondrocytes (derived from costal cartilage) has been demonstrated to be feasible and may slow disc degeneration.
|
|
| 2. |
- Brisby, Helena, 1965
(författare)
-
Nerve tissue injury markers, inflammatory mechanisms and immunologic factors in lumbar disc herniation. Clinical and experimental studies
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general concept for sciatic pain has for many decades been mechanical nerve root compression caused by a herniated disc. Recently evidence has indicated a more complex process, with a combination of mechanical and inflammatory/immunologic factors involved. The aim of these investigations was to analyze markers of nerve tissue injury, inflammation and immunologic factors in cerebrospinal fluid (CSF) and serum in patients with sciatica. Furthermore, the aim was to analyze the possible role of such inflammatory and immunologic factors in the pathophysiology of lumbar disc herniation and sciatica. The concentrations of four nerve tissue injury markers, neurofilament (NFL), S-100, glial fibrillary acidic protein (GFAp) and neuron specific enolase (NSE), were measured in CSF in patients with lumbar disc herniation and compared to control patients. The concentrations of NFL and S-100 were increased in CSF from patients with lumbar disc herniation, preferably in patients with short pain duration. In a disc herniation model in pig, changes in these nerve tissue injury markers, total protein and immunoglobulins were investigated in CSF. Nerve root compression was shown to induce an increase of NFL in CSF. Concentrations of five proinflammatory cytokines, IL-1b, IL-6, IL-8, IFN-g and TNF-a were assessed in CSF and serum from patients with disc herniation. The concentration of IL-8 was increased in CSF in 1/3 of the disc herniation patients, preferably in those with short pain duration. The involvement of nitric oxide (NO) in nucleus pulposus (NP) induced effects on spinal nerve roots were investigated in two animal models. Evidence was found for involvement of NO. The presence of auto-antibodies against glycosphingolipids was investigated in three groups of patients with sciatica. Increased serum titers of glycosphingolipid antibodies were found in approximately 2/3 of these patients. In summary, biomarkers of nerve root injury related to compression, inflammation and activation of the immune system can be detected in CSF and serum from patients with disc herniation, as well as in animal experimental models of disc herniation. Both inflammatory and immunologic mechanisms seem to be involved in the pathophysiology of sciatica caused by disc herniation.
|
|
| 3. |
- Brisby, Helena, 1965, et al.
(författare)
-
Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica.
- 2002
-
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
-
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.
|
|
| 4. |
- Cornefjord, M., et al.
(författare)
-
Cerebrospinal fluid biomarkers in experimental spinal nerve root injury
- 2004
-
Ingår i: Spine. - 1528-1159. ; 29:17, s. 1862-8
-
Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Cerebrospinal fluid biomarkers were evaluated in a setup using established pig models to mimic clinical disc herniation. OBJECTIVES: To investigate biomarkers for nerve tissue injury, inflammation, and pain in cerebrospinal fluid after mechanical compression and/or nucleus pulposus application to spinal nerve roots. SUMMARY OF BACKGROUND DATA: The association between mechanical compression, biochemical effects of nucleus pulposus, and nerve root injury in degenerative disc disorders is incompletely investigated. METHODS: The unilateral S1 nerve root was exposed in 20 pigs. The animals were divided into four groups (n = 5 each): 1) slow-onset mechanical compression with an ameroid constrictor; 2) autologous nucleus pulposus application; 3) mechanical compression plus nucleus pulposus; and 4) sham operation. After 1 week, 6 mL of cerebrospinal fluid was collected, and four structural nerve proteins, neurofilaments, S-100, glial fibrillary acidic protein, neuron-specific enolase, the proinflammatory cytokine interleukin-8, the neurotransmitter nociceptin, and substance P endopeptidase activity were analyzed using immunoassays. RESULTS: The concentration of neurofilament was increased in the mechanical compression group (17.0 microg/L +/- 5.0) and in the mechanical compression plus nucleus pulposus group (19.8 +/- 12.1 microg/L) compared with the sham group (0.9 +/- 0.9 microg/L) and the nucleus pulposus group (0.4 +/- 0.1 microg/L) (P < 0.01 for both). The concentration of nociceptin was increased significantly in the mechanical compression group (24.0 +/- 8.6 fm/mL) and in the mechanical compression plus nucleus pulposus group (31.2 +/- 6.6 fm/mL) compared with the sham group (7.0 +/- 1.3 fm/mL) (P < 0.05 and P < 0.01, respectively). A correlation was found between concentrations of neurofilament and nociceptin (r = 0.50, P < 0.05). There were no intergroup differences regarding glial fibrillary acidic protein, neuron-specific enolase, S-100, interleukin-8, or substance P endopeptidase activity. CONCLUSIONS: The present study demonstrates increased concentrations of neurofilament and nociceptin in cerebrospinal fluid after nerve root compression. A simultaneous application of nucleus pulposus did not increase the response.
|
|
| 5. |
- Gorman, D. J., et al.
(författare)
-
When is spinal pain "neuropathic"?
- 2004
-
Ingår i: Orthop Clin North Am. - 0030-5898. ; 35:1, s. 73-84
-
Tidskriftsartikel (refereegranskat)abstract
- Although one cannot always determine when a patient's persistent pain is neuropathic, the issues are becoming clearer. Patients with spinal pain need to be examined carefully and the persistence of pain should not necessarily be considered to indicate a continuing search for a nociceptive focus. Similarly, continuing pain following successful surgery may be caused by persistent spinal or central neurologic changes. New methods for characterizing the site of neural changes will develop--functional MRI and PET scanning are now characterizing brain activity and will possibly yield results soon that will be helpful in the clinic. Further work needs to be done to identify which clinical features lead to better responses to agents for the treatment of neuropathic pain. New, more specific agents with actions focused on the specific parts of neural transmission are being developed. These include agents (such as growth factors) that will cure, not just suppress, the pathologic pain generators and pathways in patients with persistent pain.
|
|
