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Biomedical subjects

K Olmarker

Publications and source records attributed to K Olmarker.

At least 37 records · Page 2Linked to original sources
PubMed1999

Markers of nerve tissue injury in the cerebrospinal fluid in patients with lumbar disc herniation and sciatica.

STUDY DESIGN: The light subunit of neurofilament protein, S-100 protein, neuron-specific enolase, and glial fibrillary acidic protein were determined in the cerebrospinal fluid in patients with lumbar disc herniation and in control patients. OBJECTIVES: To determine whether nerve root injury caused by disc herniation increases the levels of nerve and glial cell injury markers in the cerebrospinal fluid. SUMMARY OF BACKGROUND DATA: Markers of nerve tissue injury can be analyzed in the cerebrospinal fluid, allowing characterization of the cell types involved and the degree of disease in patients with neurologic disorders. METHODS: Cerebrospinal fluid samples were obtained by preoperative lumbar puncture in patients who underwent surgery for lumbar disc herniation and in patients who underwent lower extremity surgery (control group), neurofilament protein (light subunit) and glial fibrillary acidic protein were analyzed by enzyme-linked immunosorbent assay and S-100 protein and neuron-specific enolase by radioimmunoassay and luminescence immunoassay, respectively. In the disc herniation group the concentrations of the four markers were evaluated regarding possible correlation to patient history, computed tomographic findings, and clinical findings. RESULTS: Cerebrospinal fluid concentration of neurofilament protein (light subunit) and S-100 were increased in the disc herniation group compared with that in control subjects (1158 +/- 383 ng/L vs. 152 +/- 14 ng/L, P < 0.01; 1963 +/- 231 ng/L vs. 1003 +/- 152 ng/L, P < 0.05, respectively). No statistical differences in neuron-specific enolase and glial fibrillary acidic protein concentrations were observed between the groups. Disc herniation patients with fewer than 3 months' duration of subjective symptoms had higher neurofilament protein levels than did patients with longer duration. None of the markers was related to preoperative clinical or computed tomographic findings. Patients with persistent neurologic findings at follow-up 2-3 months after surgery had higher levels of neurofilament protein before surgery compared with-those without sequelae. CONCLUSIONS: Patients with disc herniation and sciatica have increased concentrations of neurofilament protein and S-100 in the cerebrospinal fluid, which indicates damage of axons and Schwann cells in the affected nerve root.

Adult↗
PubMed1999

Nucleus pulposus-induced nerve root injury: relationship between blood flow and motor nerve conduction velocity.

OBJECTIVE: It is well known that nucleus pulposus induces nerve root injury. The aim of this study was to assess the relationship between intraneural blood flow and motor nerve conduction velocity (NCV) after incision of the adjacent disc. METHODS: A total of 65 dogs were used. A left hemilaminotomy was performed, the annulus fibrosus of the L6-L7 intervertebral disc was incised, and nucleus pulposus was gently pushed into the epidural space by saline solution injection. A left hemilaminotomy without disc incision was used as the sham operation. Seven dogs were used for incision and five dogs for sham treatment for each of the following time points: 1 day, 3 days, 1 week, 1 month, and 2 months of exposure. Five additional dogs were used to establish baseline data. Blood flow in the nerve root was measured in the left L7 nerve root with a tissue blood flowmeter, using an electrolytic hydrogen clearance method. Motor NCV over the exposed area of the nerve root was measured using a neurophysiological technique. RESULTS: There was a reduction in blood flow in the nerve root after disc incision that began after 1 day and was maximal after 1 week. This reduction had resolved by 1 month, however. The motor NCV showed a reduction pattern similar to that for blood flow in the nerve root, but reduction did not begin until 3 days after disc incision and was not fully resolved until 2 months. CONCLUSION: This study demonstrates that the reduction and recovery of motor NCV are related to, and preceded by, a reduction in blood flow in the nerve root. The data might provide important information regarding the basic pathophysiological mechanisms of nucleus pulposus-induced nerve root injury.

Animals↗
PubMed1998

[New information concerning pain caused by herniated disk and sciatica. Exposure to disk tissue sensitizes the nerve roots].

Sciatica has long been considered to be solely due to mechanical deformation (compression) of a spinal nerve root by herniating disc tissue. However, recent experimental findings have demonstrated that, even in the absence of mechanical insult, nucleus pulposus-related substances may not only induce significant structural and functional injury to the adjacent nerve root, but also sensitise the nerve root, producing pain in the event of subsequent root compression. Although neither the specific mechanisms nor the active nucleus pulposus-related substances causing pain have yet been identified, the recent findings suggest that the future may well bring new pharmacological treatment alternatives for sciatica and disc herniation.

Animals↗
PubMed1998

Acute effects of nucleus pulposus on blood flow and endoneurial fluid pressure in rat dorsal root ganglia.

STUDY DESIGN: An experimental study to elucidate the initial factors in the pathogenesis of lumbar pain caused by disc herniation. OBJECTIVE: To evaluate the effects of autologous nucleus pulposus on blood flow and endoneurial fluid pressure in dorsal root ganglia. SUMMARY OF BACKGROUND DATA: Human sciatica is known to be associated with compression of lumbar nerve roots and dorsal root ganglia by herniated intervertebral discs. Recently, it has been shown that application of nucleus pulposus to nerve roots induces injury and pain-related behavior in experimental animals. In this study, the authors hypothesized that nucleus pulposus applied to a nerve root would cause increased intraneural edema and reduced blood flow in the corresponding dorsal root ganglia. Studies in peripheral nerves have shown that these initial pathophysiologic disturbances initiate complex events that exacerbate nerve injury and cause pain. METHODS: A total of 29 adult female Sprague-Dawley rats weighing 200 to 250 g had their left L5 nerve roots and associated dorsal root ganglia exposed. Autologous nucleus pulposus was harvested from the tail and applied to the L5 nerve root just proximally to the dorsal root ganglia (nucleus pulposus group). For control, the same volume of muscle was harvested from the surgical area in the back and applied similarly to the neural tissue (control group). Blood flow was continuously monitored using a laser Doppler flow probe for 3 hours (n = 10) or 4 hours (n = 8) in animals with indwelling cannulas for measurement of systemic arterial pressure. Endoneurial fluid pressures were recorded with a servonull micropipette system using glass micropipettes with tip diameters of 4 microns. Endoneurial fluid pressure in the dorsal root ganglia was measured before and 3 hours after application of nucleus pulposus (n = 7) or muscle (n = 4). After measurement of blood flow and endoneurial fluid pressure, the nerve root and dorsal root ganglia were processed for histology and evaluated by light microscope. RESULTS: Blood flow in the nucleus pulposus group was reduced by 10% to 20% from the initial value after 3 to 4 hours. This reduction was statistically significant compared with that of the control group (P < 0.01). Endoneurial fluid pressure was initially 2.6 +/- 1.2 cm H2O in the nucleus pulposus group, and 2.1 +/- 0.6 cm H2O in the control group. Three hours after application, endoneurial fluid pressure was 7.5 +/- 4.6 in the nucleus pulposus group (P > 0.05), and 2.0 +/- 0.8 in the control group (P > 0.05). Edema was the principal pathologic finding seen consistently in the nerve roots and in many of the associated dorsal root ganglia from animals treated with nucleus pulposus. CONCLUSION: Application of nucleus pulposus to nerve root increased endoneurial fluid pressure and decreased blood flow in the dorsal root ganglia. This study's acute observations in the dorsal root ganglia may thus help to explain why disc herniations without compression of neural tissue are sometimes painful because similar pathologic findings are observed after only nucleus pulposus application to the nerve root. The authors further suggest that exposure of nerve roots to nucleus pulposus may establish a "compartment syndrome" in the dorsal root ganglia.

Animals↗
PubMed1998

Tumor necrosis factor alpha and nucleus-pulposus-induced nerve root injury.

STUDY DESIGN: The effects of nucleus pulposus and various treatments to block tumor necrosis factor alpha activity were evaluated in an experimental set-up using immunohistochemistry and nerve conduction velocity recordings. OBJECTIVES: To assess the presence of tumor necrosis factor alpha in pig nucleus pulposus cells, and to see if block of tumor necrosis factor alpha also blocks the nucleus-pulposus-induced reduction of nerve root conduction velocity. SUMMARY AND BACKGROUND DATA: A meta-analysis of observed effects induced by nucleus pulposus revealed that these effects might relate to one specific cytokine-tumor necrosis factor alpha. METHODS: Series-1: Cultured nucleus pulposus cells were stained immunohistologically with a monoclonal antibody for tumor necrosis factor alpha. Series-2: Nucleus pulposus was harvested from lumbar discs and applied to the sacrococcygeal cauda equina in 13 pigs autologously. Four pigs received 100 mg of doxycycline intravenously; five pigs had a blocking monoclonal antibody to tumor necrosis factor alpha applied locally in the nucleus pulposus, and four pigs remained nontreated, forming a control group. Three days after the application, the nerve root conduction velocity was determined over the application zone by local electrical stimulation. RESULTS: Series-1: Tumor necrosis factor alpha was found to be present in the nucleus pulposus cells. Series-2: The selective antibody to tumor necrosis factor alpha limited the reduction of nerve conduction velocity, although in comparison with the control group this was not statistically significant. However, treatment with doxycycline significantly blocked the nucleus-pulposus-induced reduction of conduction velocity. CONCLUSION: For the first time, a specific substance, tumor necrosis factor alpha, has been linked to the nucleus-pulposus-induced effects of nerve roots after local application. Although the effects of this substance may be synergistic with those of other similar substances, the data of the current study may be of significant importance for the continued understanding of nucleus pulposus' biologic activity, and of possible potential use for future strategies in managing sciatica.

Animals↗
PubMed1998

Effects of lidocaine on nucleus pulposus-induced nerve root injury. A neurophysiologic and histologic study of the pig cauda equina.

STUDY DESIGN: Application of autologous nucleus pulposus on nerve roots and treatment with local application of lidocaine in the pig. OBJECTIVES: Studies of the effects of lidocaine on nucleus pulposus-exposed nerve roots. SUMMARY OF BACKGROUND DATA: Nerve root infiltration may improve radicular symptoms beyond the pharmacologic duration of local anesthetics, but the mechanisms for this effect are not known. METHODS: Nucleus pulposus was harvested from a lumbar disc and placed onto the sacrococcygeal cauda equina in pigs. In Series 1, early lidocaine treatment of nucleus pulposus-induced nerve root injury, pigs received 2% lidocaine (n = 5) or saline (n = 5) before and after surgery. Nerve conduction velocity and histologic appearance were studied after 3 days. In Series 2, delayed lidocaine treatment of nucleus pulposus-induced nerve root injury, after 7 days 2% lidocaine was administered epidurally to nucleus pulposus-exposed (n = 4) and -nonexposed (n = 4) nerve roots. Nerve conduction velocity, muscle action potentials, and histologic appearance were assessed. RESULTS: In Series 1, early treatment with lidocaine limited the reduction in nerve conduction velocity. The epidural inflammation was less in lidocaine treated animals. In Series 2, nerve conduction velocity was lower in nucleus pulposus-exposed animals than in nonexposed animals. The initial reduction of nerve conduction velocity and muscle action potential was similar between the groups, but the recovery of muscle action potential was slower and less complete in nucleus pulposus-exposed nerve roots. There was minimal histologic nerve injury in both series and in both protocols. CONCLUSIONS: Early treatment with lidocaine may reduce nucleus pulposus-induced nerve root injury. Lidocaine induced a delayed recovery in nerve roots exposed to nucleus pulposus. Further studies are needed to clarify the therapeutic effects of nerve root infiltration and the pathophysiology of nucleus pulposus-induced nerve root injury.

Anesthetics, Local↗
PubMed1998

Cultured, autologous nucleus pulposus cells induce functional changes in spinal nerve roots.

STUDY DESIGN: Nerve conduction velocity in pig nerve roots was assessed after application of various preparations of nucleus pulposus and control. OBJECTIVE: To study whether cultured nucleus pulposus cells could reduce nerve conduction velocity after epidural application. SUMMARY OF BACKGROUND DATA: It is known that nucleus pulposus applied epidurally may reduce the nerve conduction velocity of the adjacent nerve roots and that this reduction seems to be related to the cells of the nucleus pulposus. METHODS: Nucleus pulposus cells and fibroblasts were cultured for 3 weeks, and various preparations were applied to the cauda equina in 29 pigs. The cells were always from the same animals from which they had been harvested. After 1 week, nerve conduction velocity was determined by local electrical stimulation. RESULTS: Application of live fibroblasts and conditioned culture medium from the nucleus pulposus cell culture dishes did not induce significant reduction of conduction velocity, compared with application of dead fibroblasts, which served as control. However, application of live and dead nucleus pulposus cells induced significant reductions. CONCLUSIONS: Application of nucleus pulposus cells reproduced the previously seen reduction in nerve conduction velocity induced by nonmodified nucleus pulposus. Because membranes of the nucleus pulposus cells had similar effects, it can be assumed that the effects are related to membrane-bound substances or structures.

Animals↗
PubMed1998

Chronic double-level cauda equina compression. An experimental study on the dog cauda equina with analyses of nerve conduction velocity.

STUDY DESIGN: Nerve conduction velocity was studied in the dog cauda equina subjected to chronic double-level compression. OBJECTIVES: To analyze the effects of chronic double-level cauda equina compression. SUMMARY OF BACKGROUND DATA: Double-level cauda equina compression produces more symptoms in patients and more changes in acute experimental set-ups than does single-level compression. However, there have been no controlled, experimental studies on chronic double-level compression. METHODS: A total of 20 dogs were anesthetized. Two balloons were placed under the lamina of the seventh lumbar vertebra and the first sacral vertebra, respectively. One week (10 mm Hg, n = 5; 0 mm Hg, n = 5) and 1 month (10 mm Hg, n = 5; 0 mm Hg, n = 5) after inflation with a viscous substance, nerve conduction velocity was studied by local electrical stimulation and recording of muscle action potentials in the tail muscles. RESULTS: Nerve conduction velocity was determined over the cranial balloon, the caudal balloon, and both balloons. The data were similar for all three recordings. After 1 week there was a significant reduction in nerve conduction velocity induced by 10 mm Hg, compared with that induced by 0 mm Hg, which showed normal conditions. However, after 1 month this initial reduction in nerve conduction velocity had recovered partially. The reduction was similar to that described for single-level compression in a previous study in which the same compression model was used. CONCLUSIONS: Unlike the acute situation, chronic double-level compression does not induce more changes than single-level compression after 1 week, although the recovery after 1 month of compression is less complete after double-level compression. This less complete recovery may be a result of an adaptation of the nerve tissue and the vascularization of the cauda equina nerve roots to the applied pressure.

Action Potentials↗
PubMed1998

Walking analysis of rats subjected to experimental disc herniation.

In an attempt to evaluate whether experimental disc herniation can result in changes in walking pattern, presumably indicating pain, four groups of rats - sham (n = 5), disc puncture (NP, n = 5), displacement of nerve root and ganglion (DIS, n = 5), and the combination of disc puncture and displacement (NP + DIS, n = 6) - were assessed when walking in a Plexiglas corridor at day 2-14 after surgery. All surgical procedures were performed at the L4-5 level on the left side. Step length analysis showed that rats in the NP and DIS series had no difference between the legs initially, but a tendency towards slightly shorter left steps at day 8-12, whereas the animals in the NP + DIS series had slightly shorter right steps day 2-10. However, no statistically significant differences compared with the sham series could be detected for any of the groups. Nerve dysfunction on the operated side was only observed on one occasion in two rats and on 2 days in one rat, all from the NP + DIS series. Apparent limping was seen in three of the animals in the NP + DIS series and in one in the DIS series. Limping and nerve dysfunction only co-incided on one occasion out of a total of 13 observations of limping, suggesting that the limping was induced by pain and not neurologic deficit. In conclusion, the combination of epidural nucleus pulposus and displacement induced a limping whereas nucleus pulposus or displacment alone did not. Assessment of limping thus seemed to provide adequate information of presence of pain, but step length measurement did not provide any useful data. Although walking analysis may be a valuable assessment of sciatic pain, better modalities must be developed to analyze experimentally induced nerve root pain.

Animals↗
PubMed1998

Early effects of nucleus pulposus application on spinal nerve root morphology and function.

It is known that 24 h or more after epidural application of autologous nucleus pulposus, functional and structural changes are established in adjacent nerve roots. It is, however, not known how soon after the application these changes appear. The aim of this study was to reduce the exposure duration to 3 h and to evaluate nerve function and histological changes in the nerve tissue during this time period. A total of 12 pigs was used. In ten pigs, autologous nucleus pulposus (NP) was applied epidurally on the cauda equina. Nerve function was then monitored for 3 h by measurements of muscle action potentials (MAP) in the tail muscles, following nerve root stimulation cranial to the exposed zone. In five of the ten pigs with NP application, nerve root compression to 50 mm Hg was added by means of an inflatable balloon. In two control animals, neither NP nor compression was applied. At the end point, nerve root specimens were harvested for histological assessment. No reduction of MAP amplitude was detected in any of the series. However, there was an epidural accumulation of leucocytes and mast cells, as well as minor axonal and Schwann cell changes in both the NP and NP+ compression series, as compared to the control series. Morphological changes in terms of an epidural inflammatory reaction and minor axonal and Schwann cell damage may thus be demonstrated within 3 h of NP application, with or without compression. However, there is no functional deterioration of the nerve roots detectable within this time period.

Animals↗
PubMed1998

[Back pain. Experimental studies are successful].

Recent experimental studies performed at the Dept of Orthopaedics at Gothenburg University have systematically assessed the basic pathophysiological mechanisms behind sciatica due to disc herniation. It has hereby been seen that the epidural presence of nucleus pulposus may induce structural and functional injury of the adjacent nerve roots similar in magnitude to those induced by mechanical deformation. By increasing the knowledge of the substances and mechanisms leading to this nucleus pulposus-induced nerve injury it may be assumed that sciatica to a certain extent may be treated by specific pharmacologic agents in the future, in combination with existing treatment modalities.

Female↗
PubMed1997

Experimental disc herniation: evaluation of the natural course.

STUDY DESIGN: Changes in L7 nerve root conduction velocity and changes in appearance on magnetic resonance study of the L6-L7 intervertebral disc in the dog were assessed for 2-6 months after an experimental disc herniation was performed. OBJECTIVES: To assess the time-related changes of nerve conduction velocity and magnetic resonance changes of the intervertebral discs. SUMMARY OF BACKGROUND DATA: It is known that nucleus pulposus may induce nerve root morphologic and functional changes when applied epidurally. However, it is not known whether such changes are reversible. METHODS: The spinal canal was opened by laminotomy of the upper part of the L7 lamina and the lower part of the L6 lamina on the left side. The L7 nerve root was gently retracted (sham) or the disc was punctured and injected with saline to produce herniation of the nucleus pulposus during the retraction time (herniation). After 1 day to 2 months, nerve root conduction velocity was determined by local electrical stimulation. Six dogs had the herniation or the sham procedure, and the L6-L7 disc was studied by magnetic resonance imaging at various times up to 6 months after the procedure. RESULTS: Decrease in nerve conduction velocity reached a maximum after 7 days and recovered to baseline level fully within 2 months. Although there was a clear reduction-recovery pattern, the difference in conduction velocity compared with that of the sham group was statistically significant after only 7 days. Disc degeneration started in the herniated discs within 7 days after the herniation procedure. However, none of the experimentally induced disc herniations were visualized by magnetic resonance imaging 7 days after the procedure. In no case was there subsequent nerve root compression. In one case, disc protrusion was visible 6 months after the herniation procedure. CONCLUSIONS: The results demonstrate for the first time that nucleus pulposus-induced nerve root injury reverses in 2 months and that it may be present without simultaneous nerve root compression, as confirmed by findings in magnetic resonance imaging. The previously described nucleus pulposus-induced nerve root changes may therefore be of clinical importance, and experimental studies of these mechanisms will probably be relevant for expanded understanding of the pathophysiologic mechanism behind sciatica that is caused by disc herniation.

Animals↗
PubMed1997

A model for chronic nerve root compression studies. Presentation of a porcine model for controlled, slow-onset compression with analyses of anatomic aspects, compression onset rate, and morphologic and neurophysiologic effects.

STUDY DESIGN: Compression onset rate, anatomic aspects, and morphologic and neurophysiologic effects in spinal nerve roots were studied in a nerve root compression model in pigs. OBJECTIVES: To analyze the compression onset rate by measuring the gradual reduction of the inner diameter of the constrictor, the motor nerve conduction velocity by electromyography, the morphologic changes by light microscopy, and the gross and vascular anatomy by dissection and ink injections, respectively, in a model for experimental chronic nerve root compression. SUMMARY OF BACKGROUND DATA: Chronic nerve root compression is recognized to be related to back pain syndromes, including sciatica. Various aspects of morphologic and physiologic changes have been studied previously in models for acute compression and chronic nerve root irritation, but a controlled, graded chronic nerve root compression model has not been described. METHODS: An ameroid constrictor was applied around a spinal nerve root just cranial to the dorsal root ganglion. The inner diameter of this constrictor gradually becomes reduced. After 1 week or 4 weeks, electromyographic measurements were performed, and tissue samples were harvested for histologic analyses. The gross and vascular anatomy of the pigs' spinal nerve roots were studied by dissection and ink injections. RESULTS: There was a statistically significant decrease in the nerve conduction velocity in compressed compared with noncompressed spinal nerve roots after 1 week and after 4 weeks. The ameroid constrictors induced nerve fiber damage, endoneural hyperemia, bleeding, and inflammation at the compression zone. There was often a severe reduction in the number of myelinated fibers after 4 weeks. CONCLUSION: A model for controlled, chronic, partial nerve root injury using a gradual compression-onset constrictor is presented. This model allows for induction of a controlled graded chronic nerve root injury and can be used for research on basic pathophysiologic mechanisms and on the effects of various interventions on nerve root injury development.

Animals↗
PubMed1997

The effects of normal, frozen, and hyaluronidase-digested nucleus pulposus on nerve root structure and function.

STUDY DESIGN: Autologous nucleus pulposus was modified and applied to the cauda equina in pigs. Histology and neurophysiology were assessed after 7 days. OBJECTIVES: To assess if alterations of the nucleus pulposus would change the degree and distribution of the nerve injury induced by autologous nucleus pulposus. SUMMARY OF BACKGROUND DATA: It was reported recently that nucleus pulposus may induce structural and functional changes in nerve roots after epidural application. The basic mechanisms causing these changes are not fully understood. METHODS: Nucleus pulposus was harvested from lumbar discs and submitted to either of three treatments; 37 C for 24 hours (n = 5), -20 C for 24 hours (n = 5), or digestion by hyaluronidase for 24 hours (n = 6). In two additional pigs, nucleus pulposus was applied just after harvest as a control to verify previous observations. After 7 days, nerve conduction velocity was recorded, and specimens were processed for blinded light microscopic assessment. RESULTS: When nucleus pulposus was applied just after harvest, or when it had been kept at 37 C or digested by hyaluronidase for 24 hours, there was a significant reduction in nerve conduction velocity similar to previous observations. When nucleus pulposus had been kept at -20 C for 24 hours, however, there was no reduction in conduction velocity. There were no apparent differences between the groups at the histologic assessment. Staining of the nucleus pulposus showed that the cells in the nucleus pulposus exposed to -20 C were lysed, whereas the cells in the nucleus pulposus treated by the two other methods were mainly unaffected. CONCLUSIONS: Because freezing of the nucleus pulposus probably kills the cells but does not affect other components, one may assume that the biologic effects induced by the nucleus pulposus may be related to its cell population.

Animals↗