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Biomedical subjects

B Rydevik

Publications and source records attributed to B Rydevik.

At least 37 records · Page 2Linked to original sources

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.

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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.

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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.

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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.

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Back muscle injury after posterior lumbar spine surgery. Topographic evaluation of intramuscular pressure and blood flow in the porcine back muscle during surgery.

STUDY DESIGN: Intramuscular pressure and blood flow of the back muscles were evaluated topographically during posterior lumbar spine surgery. The topographic damage of the back muscle after surgery was studied. OBJECTIVE: To investigate the relationship between intramuscular pressure or blood flow during posterior lumbar surgery and the back muscle injury after surgery. SUMMARY OF BACKGROUND DATA: Latrogenic back muscle injury in an animal and human model has been reported previously. Changes of intramuscular pressure and blood flow during surgery might be related to the muscle injury. No previous study on this issue has been published. METHODS: The contact pressure between the retractor blade and muscle tissue was monitored in 10 pigs during posterior surgery of the lumbar spine. On one side, intramuscular pressure at 5, 10, and 20 mm lateral to the retractor and on the other side blood flow of the back muscle at 5 and 20 mm during surgery were measured. Histologic changes of the back muscle at 5, 10, and 20 mm to the midline were evaluated 3 hours after surgery. RESULTS: The contact pressure decreased exponentially with time. Intramuscular pressure 5 mm lateral to the retractor was 114 +/- 31 mm Hg and was significantly higher than at 10 mm and 20 mm. Blood flow markedly decreased during surgery and recovered incompletely after releasing the retractor at 5 mm and 20 mm lateral to the retractor. Blood flow at 5 mm was significantly lower than at 20 mm throughout surgery. The muscle damage 3 hours after surgery was more severe near the retractor blade. CONCLUSIONS: The back muscles were exposed to pathophysiologic condition by a retractor during posterior lumbar spine surgery. External compression by a retractor increases intramuscular pressure to levels that impede local muscle blood flow. The muscle degeneration after surgery could be explained by direct mechanical damage and by the increased intramuscular pressure of muscle tissue by the retractor.

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Chondroitinase ABC (pharmaceutical grade) for chemonucleolysis. Functional and structural evaluation after local application on intraspinal nerve structures and blood vessels.

STUDY DESIGN: The effects on nerve tissue and blood vessels of locally applied chondroitinase ABC were studied in two experimental models using chymopapain and the vehicle of chondroitinase ABC for controls. OBJECTIVES: To assess the effects of chondroitinase ABC on blood vessels and nerve tissue after local application. SUMMARY OF BACKGROUND DATA: Chondroitinase ABC has been suggested for chemonucleolysis because it has a high specificity for nucleus pulposus matrix, which could mean a high efficiency in dissolving disc tissue combined with a low risk of side effects on other tissues. METHODS: Chondroitinase ABC or controls were injected intrathecally in the pig, and nerve conduction velocity and histologic changes were assessed after 7 days. The same substances were injected into the hamster cheek pouch and studied for 60 minutes for microvascular effects. The vehicle for the enzyme was used as a negative control and chymopapain in a therapeutic concentration served as a positive control. RESULTS: In all series there was a slight intrathecal fibrotic reaction that was most pronounced after chymopapain injection. The effects on nerve conduction velocity and nerve morphology were similar between chondroitinase ABC and its vehicle. Chymopapain induced a significant reduction in nerve conduction velocity and pronounced histologic changes. In the cheek pouch, chymopapain induced a stand-still of blood flow at the injection site, and microhemorrhage and macromolecular leakage from the vessels at the border of the injection site. Only a slightly reduced blood flow was occasionally found after injection of chondroitinase ABC and controls. CONCLUSIONS: In agreement with the current literature, these observations indicate that chondroitinase ABC is safe regarding adverse effects on nerve tissue and blood vessels. The slight reduction in conduction velocity after intrathecal injection of chondroitinase ABC or its vehicle is most likely the result of surgical injury while releasing the nerve roots from the intrathecal fibrous adhesions. Such adhesions may be related to the laminectomy per se, and probably have no pathophysiologic significance.

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Ultrastructural changes in spinal nerve roots induced by autologous nucleus pulposus.

STUDY DESIGN: Ultrastructural changes were analyzed by transmission electron microscopy in nerve roots exposed to autologous nucleus pulposus experimentally. OBJECTIVES: To assess if ultrastructural changes were present in areas with no light microscopic changes in nerve roots exposed to autologous nucleus pulposus in a pig model. SUMMARY OF BACKGROUND DATA: Previous analyses have shown that there is focal nerve fiber damage in nerve roots exposed to autologous nucleus pulposus in the pig. These changes could not fully explain the reduction in nerve conduction velocity seen in the same nerve roots. In the present study, the parts of the nerve roots that did not display breakdown of axons or myelin sheaths at the light microscopic level were analyzed regarding ultrastructural changes. METHODS: In a previous study, nucleus pulposus was harvested from a lumbar disc and placed epidurally onto the cauda equina at the sacrococcygeal level in pigs. Retroperitoneal fat was used as control. After 1, 3, and 7 days, the nerve roots were excised and processed for light microscopy. Parts of the nerve roots that appeared normal at the light microscopic level were further processed for the present electron microscopic examination. RESULTS: Significant ultrastructural changes, such as expansion of the Schwann cell cytoplasm and intracellular edema with vesicular swelling of the Schmidt-Lanterman incisures, were observed in nerve fibers with normal axons. Although present after nucleus pulposus and control application, the changes were more pronounced after the application of nucleus pulposus. CONCLUSIONS: Epidural application of autologous nucleus pulposus without any pressure may induce not only nerve function impairment but also axonal injury and significant primary Schwann cell damage with vesicular swelling of Schmidt-Lanterman incisures. However, because axonal and Schwann cell changes affected only part of the nerve fibers, further causes of the impaired nerve conduction need to be determined.

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Spinal nerve root compression.

The pathophysiology of sciatica is not completely understood, although our understanding of its causes is increasing. Mechanical alterations combined with inflammatory changes lead to pain. Compression alters nerve root conduction and compromises the nutritional support of spinal nerve roots (through intrinsic and extrinsic vascularity and cerebral spinal fluid percolation). Mechanical forces can lead to intraneural damage and functional changes in nerve roots. Chemical and metabolic effects can create an inflammatory response. Varying causes of inflammation coupled with varying degrees of compression can occur anywhere along the cauda equina or spinal nerve root, including the dorsal root ganglia, and contribute to the pain response and neurologic deficits associated with sciatica.

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Intermittent cauda equina compression. An experimental study of the porcine cauda equina with analyses of nerve impulse conduction properties.

STUDY DESIGN: Neurophysiologic reactions of cauda equina nerve roots to intermittently applied compression were assessed for two different modes of compression using a porcine model. OBJECTIVE: To assess the neurophysiologic reactions of cauda equina nerve roots to intermittently applied compression. SUMMARY OF BACKGROUND DATA: A number of experimental studies have been presented recently regarding the reaction pattern of spinal nerve roots to compression. These studies have used a continuous pressure level. For studies of pathophysiologic mechanisms behind neurogenic claudication, however, it would be more relevant to study the effects of intermittently applied compression. METHODS: The cauda equina was exposed and compression was applied by two inflatable balloons. Two different modes of compression were used. Either the two balloons were inflated and deflated simultaneously (intermittent compression), or just the caudal balloon was inflated and deflated while the cranial balloon was kept continuously inflated (continuous/intermittent compression). The experimental series were: intermittent compression at 10 mm Hg (n = 5) and 50 mm Hg (n = 5), and continuous/intermittent compression at 10 mm Hg (n = 5) and 50 mm Hg (n = 5). For both modes of compression the pressure in the balloons with intermittent inflation was maintained for 10 minutes and deflated for 5 minutes. This procedure was repeated in 8 cycles for 2 hours. Muscle action potentials were recorded in the tail muscles. RESULTS: Compression at 10 mm Hg induced similar reductions of muscle action potentials for both compression modes. At 50 mm Hg, the effects were more pronounced at continuous/intermittent compression than at intermittent compression. The reduction of muscle action potentials was slightly more pronounced for 50 than for 10 mm Hg at intermittent compression. However, a statistically significant difference in the results was found only between 10 and 50 mm Hg at the continuous/intermittent compression mode. CONCLUSIONS: The established model allows investigation of the effects of intermittent cauda equina compression, which might be clinically more relevant than continuous compression regarding the pathophysiologic mechanisms behind neurogenic claudication.

Action Potentials↗

Inflammatogenic properties of nucleus pulposus.

STUDY DESIGN: The inflammatogenic properties of nucleus pulposus were assessed in two experimental models previously used for screening of inflammatogenic properties of other substances. This study was performed to assess the inflammatogenic properties of nucleus pulposus in models previously screened for other substances. SUMMARY OF BACKGROUND DATA: Previous experimental studies, as well as clinical observations, have indicated that inflammatory mechanisms may constitute an important pathogenetic component in sciatica due to herniation of the nucleus pulposus. METHODS: In the first experimental series, autologous nucleus pulposus and retroperitoneal fat were placed in perforated titanium chambers, which were placed subcutaneously in pigs, together with an empty chamber as sham. After 7 days, the number of leukocytes in the chambers was determined. In the second experimental series, the microvascular reactions were studied by vital microscopy of the hamster cheek-pouch after local injections of suspensions of homologous nucleus pulposus and homologous subcutaneous fat. Macromolecular extravascular leakage was studied by fluorescence microscopy using FITC-dextran as a tracer. RESULTS: The leukocyte ratio between fat control and sham was 0.9 +/- 0.6 and between nucleus pulposus and sham 2.4 +/- 0.7. The nucleus pulposus thus attracted significantly more leukocytes than fat. Injection of nucleus pulposus suspension induced thrombosis formation and pronounced leakages of macromolecules in a majority of the injection sites. However, injection of vehicle and fat suspension in the cheek-pouch only resulted in minor vital microscopic changes. CONCLUSIONS: Nucleus pulposus demonstrated inflammatogenic properties as indicated by leukotaxis and an increase of vascular permeability. It was not clear, however, it these reactions were induced by substances from the nucleus pulposus per se or from substances being liberated from other tissues as a response to an interaction with components of the nucleus pulposus.

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Neuropeptide changes in compressed spinal nerve roots.

STUDY DESIGN: Compression-induced changes in the concentration of substance P and VIP (vasoactive intestinal polypeptide), in spinal nerve roots and dorsal root ganglia were studied in an experimental nerve root compression model in pigs. OBJECTIVES: To analyze by radioimmunoassay the concentration of the neuropeptides substance P and VIP in a model for experimental chronic nerve root compression. SUMMARY OF BACKGROUND DATA: Neuropeptides such as substance P and VIP seem to be involved in the transmission of pain and changes in the levels of these neuropeptides have been described in models where peripheral or spinal nerve injury was induced. METHODS: An ameroid constrictor was applied on a spinal nerve root just cranial to the dorsal root ganglion. The inner diameter of this constrictor is gradually reduced. After 1 or 4 weeks, tissue samples were taken from the nerve root cranial to the constrictor and from the dorsal root ganglion for measurement of substance P and VIP concentrations. RESULTS: There was a statistically significant increase in substance P concentrations in the compressed dorsal root ganglia when compared to the noncompressed dorsal root ganglia at both 1 and 4 weeks. Substance P concentration was also significantly increased in the nerve root after 1 but not after 4 weeks. The VIP levels were not significantly changed in either tissue. CONCLUSIONS: The results of the study indicates an increase in substance P levels in the dorsal root ganglion (after 1 and 4 weeks) and in the nerve root (after 1 week) in a model for chronic nerve root compression in pigs. There were no significant differences in the VIP concentrations. The study thus indicates that changes in substance P are related to experimental chronic nerve root compression.

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A rapid transport route between the epidural space and the intraneural capillaries of the nerve roots.

STUDY DESIGN: The possibility of epidurally applied substances reaching the intraneural capillaries of the spinal nerve roots and cauda equina was assessed in the pig sacrococcygeal spine. METHODS: The presence of Evans blue-labelled albumin in intraneural capillaries after epidural application for 1, 10, or 30 minutes was studied with fluorescence microscopy. Ink angiography was used to determine whether there were any direct communicating vessels between the epidural vein plexus and the intraneural capillaries. RESULTS: Evans blue-labelled albumin was present in the intraneural capillaries 1 minute after epidural application. Microangiography demonstrated small venules that connected the epidural vein plexus and the intraneural capillaries. CONCLUSIONS: The results of this study demonstrated a rapid transport route between the epidural space and the intraneural capillaries. The results suggest that nucleus pulposus material, as well as epidurally applied substances, such as local anesthetic drugs or epidurally injected corticosteroids, may have a rapid, direct transport route to the axons of the spinal nerve roots. The demonstrated transport route also may be related to the mechanisms behind epidural anesthesia and spinal nerve root infiltration.

Albumins↗

Effects of methylprednisolone on nucleus pulposus-induced nerve root injury.

STUDY DESIGN: The effects of intervention by intravenous injection of methylprednisolone to reduce the nerve root injury after epidural application of autologous nucleus pulposus was studied in an experimental model on the pig cauda equina in 20 animals. METHODS: Nucleus pulposus was harvested from a lumbar disc. After lowering the pH of the nucleus pulposus to 3.5 it was placed onto the sacrococcygeal cauda equina. Fifteen of the pigs received a single intravenous injection of 30 mg/kg methylprednisolone, 5 minutes, 24 hours, or 48 hours, respectively, after the application. After 7 days, the nerve conduction velocity was determined, and biopsies of the cauda equina was examined by lightmicroscopy. RESULTS: In the five pigs that did not receive any methylprednisolone treatment, nerve conduction velocity was reduced, whereas it was normal in the pigs treated 5 minutes and 24 hours after nucleus pulposus application. In pigs treated after 48 hours, nerve conduction velocity was reduced only slightly. At the light microscopic level, significant changes occurred in all series. CONCLUSIONS: This study indicates that the nucleus pulposus-induced effects on nerve function in an experimental pig model may be reduced dramatically by high-dose methylprednisolone administration within 24-48 hours after epidural application of autologous nucleus pulposus. The light microscopic changes were probably not significant for the nerve function. Instead, a morphologic explanation on a subcellular level should probably be sought.

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The European Spine Society AcroMed Prize 1994. Acute thermal nerve root injury.

Bone cement is sometimes used for vertebral body reconstruction following tumor removal. During such procedures, the polymerization of the methyl-metacrylate in the bone cement generates heat. Such temperature increase might cause damage to the nerve roots within the spinal canal. In the present study, pig cauda equina nerve roots were subjected to controlled temperature increases by means of a heat-generating probe. A temperature of 40 degrees C applied for 5 min did not cause any changes in nerve root function. However, 70 degrees C resulted in a complete block of nerve root function within 5 min. Histological nerve fiber damage was seen after exposure to 60 degrees C and 70 degrees C. The present study provides basic knowledge of heat-resistance properties of spinal nerve roots that might be directly applicable as guidelines for safety margins during surgical spine reconstruction procedures using bone cement.

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[Sciatica and herniated disk. Current aspects of pathophysiology and pain mechanisms].

Pathoanatomical and pathophysiological aspects of spinal nerve roots involved in disk herniation are discussed, and recent advances in our understanding of nerve root physiology and pathophysiology summarised. Evidence is presented suggesting that nerve roots may be affected not only by mechanical compression but also by nucleus pulposus tissue via biochemical mechanisms. Clinical symptoms are also discussed, as are recent findings regarding the diagnosis and treatment of disk herniation and sciatica.

Ganglia, Spinal↗

Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots.

Epidural application of autologous nucleus pulposus in pigs, without mechanical nerve root compression, induced a pronounced reduction in nerve conduction velocity in the cauda equina nerve roots after 1-7 days, compared to epidural application of retroperitoneal fat in control experiments. Histologically, the nerve fiber injury was more pronounced after application of nucleus pulposus than after control tissue application. The results demonstrate that nucleus pulposus may induce nerve tissue injury by mechanisms other than mechanical compression. Such mechanisms may be based on direct biochemical effects of nucleus pulposus components on nerve fiber structure and function and microvascular changes including inflammatory reactions in the nerve roots.

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Double-level cauda equina compression: an experimental study with continuous monitoring of intraneural blood flow in the porcine cauda equina.

Compression of the spinal nerve roots may occur clinically at multiple levels at the same time; however, the basic pathophysiology of multi-level compression is largely unknown. In this study, the intraneural blood flow was analyzed continuously in the uncompressed segment between two compression balloons, with a pig used as an experimental model and a thermal diffusion method. At 10 mm Hg compression, there was a 64% reduction of total blood flow in the uncompressed segment compared with pre-compression values. Total ischemia occurred at pressures 10-20 mm Hg below the mean arterial blood pressure. After two-level compression at 200 mm Hg for 10 min, there was a gradual recovery of the intraneural blood flow towards the baseline. Recovery was less rapid and less complete after 2 h of compression. Double-level compression of the cauda equina can thus induce impairment of blood flow, not only at the compression sites, but also in the intermediate nerve segments located between two compression sites, even at very low pressures. These findings may have clinical importance in the understanding of the pathophysiology of multiple-level cauda equina compression.

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