Adam Meir

High pressures and asymmetrical stresses in the scoliotic disc in the absence of muscle loading.

BackgroundLoads acting on scoliotic spines are thought to be asymmetric and involved in progression of the scoliotic deformity; abnormal loading patterns lead to changes in bone and disc cell activity and hence to vertebral body and disc wedging. At present however there are no direct measurements of intradiscal stresses or pressures in scoliotic spines. The aim of this study was to obtain quantitative measurements of the intradiscal stress environment in scoliotic intervertebral discs and to determine if loads acting across the scoliotic spine are asymmetric. We performed in vivo measurements of stresses across the intervertebral disc in patients with scoliosis, both parallel (termed horizontal) and perpendicular (termed vertical) to the end plate, using a side mounted pressure transducer (stress profilometry)MethodsStress profilometry was used to measure horizontal and vertical stresses at 5 mm intervals across 25 intervertebral discs of 7 scoliotic patients during anterior reconstructive surgery. A state of hydrostatic pressure was defined by identical horizontal and vertical stresses for at least two consecutive readings. Results were compared with similar stress profiles measured during surgery across 10 discs of 4 spines with no lateral curvature and with data from the literature.ResultsProfiles across scoliotic discs were very different from those of normal, young, healthy discs of equivalent age previously presented in the literature. Hydrostatic pressure regions were only seen in 14/25 discs, extended only over a short distance. Non-scoliotic discs of equivalent age would be expected to show large centrally placed hydrostatic nuclear regions in all discs. Mean pressures were significantly greater (0.25 MPa) than those measured in other anaesthetised patients (<0.07 MPa). A stress peak was seen in the concave annulus in 13/25 discs. Stresses in the concave annulus were greater than in the convex annulus indicating asymmetric loading in these anaesthetised, recumbent patients.ConclusionIntradiscal pressures and stresses in scoliotic discs are abnormal, asymmetrical and high in magnitude even in the absence of significant applied muscle loading. The origin of these abnormal stresses is unclear.

A phenotypic comparison of proteoglycan production of intervertebral disc cells isolated from rats, rabbits, and bovine tails; which animal model is most suitable to study tissue engineering and biological repair of human disc disorders?

The nucleus pulposus (NP) of the intervertebral disc in cattle and humans shows the most dramatic changes with aging of any cartilaginous tissue. In humans, notochordal cells disappear from the NP and are replaced with chondrocytic cells by adolescence. However, notochordal cells of the NP persist into adult life in some species, such as rats and rabbits. Therefore, comparison of the metabolic activity of notochordal and nonnotochordal cells is considered to be important for determining the type of cell to use for transplantation to regenerate intervertebral discs. In this study, we investigated the notochordal NP cells of rats and rabbits, as well as nonnotochordal (chondrocyte-like) bovine NP cells, in a three-dimensional culture system to examine whether proteoglycan metabolism varied among these three cell types. As a result, bovine NP cells produced around 0.18 mg/mL of glycosaminoglycan after culture for 5 days, while rat and rabbit NP cells produced about four and two times more glycosaminoglycan than bovine cells, respectively. In conclusion, this study demonstrated marked differences of energy metabolism and production of matrix components between notochordal and nonnotochordal NP cells. Animals with notochordal cells in the NP, such as rats and rabbits, may not provide good models for investigation of biological repair and tissue engineering for human disc disorders.

Ultrastructural analysis on lumbar disc herniation using surgical specimens: role of neovascularization and macrophages in hernias.

Study Design. The mechanisms responsible for the spontaneous regression of lumbar disc herniation (LDH) were studied by examining herniated tissue collected at operation from patients with LDH. Objective. The aim of the present study was to investigate the role of neovascularization and macrophages in hernias when spontaneous regression of LDH occurred. Summary of Background Data. Spontaneous regression of LDHs has already been demonstrated by diagnostic imaging with tools such as magnetic resonance imaging. However, there have been few studies on the mechanisms of spontaneous regression based on pathologic examination of herniated tissue. In particular, there has been no detailed work on the role of macrophages, which are thought to be closely associated with spontaneous regression. Methods. The magnetic resonance imaging and operative findings of 73 patients who underwent surgery were investigated, and specimens collected during surgery were examined by light and transmission electron microscopy. Results. Capillaries that invade the hernia and macrophages derived from monocytes migrating out of these capillaries are considered to be important factors in the regression of the herniated disc. Macrophages contain lysosomes filled with collagen-degrading enzymes that break down substances after phagocytosis, whereas primary lysosomes are secreted by these cells and break down intercellular substances such as collagen. Both of these mechanisms are closely involved in the regression of herniation. Conclusion. The inflammatory response that occurs around hernia tissue in the epidural space is believed to play an important role in herniated disc resorption, although it may also have a harmful effect on the adjacent nerve root. Therefore, control of the inflammatory reac-tion is an important challenge when treating patients with disc herniation.

The internal pressure and stress environment of the scoliotic intervertebral disc--a review.

Abstract The aetiology, in terms of both initiation and progression, of the deformity in idiopathic scoliosis is at present unclear. Even in neuromuscular cases, the mechanisms underlying progression are not fully elucidated. It is thought, however, that asymmetrical loading is involved in the progression of the disease, with evidence mainly from animal studies and modelling. There is, however, very little direct information as to the origin or mechanism of action of these forces in the scoliotic spine. This review describes the concept of intervertebral disc pressure or stress and examines possible measurement techniques. The biological and mechanical consequences of abnormalities in these parameters are described. Future possible studies and their clinical significance are also briefly discussed. Techniques of pressure measurement have culminated in the development of ‘pressure profilometry’, which provides stress profiles across the disc in mutually perpendicular axes. A hydrated intervertebral disc exhibits mainly hydrostatic behaviour. However, in pathological states such as degeneration and scoliosis, non-hydrostatic behaviour predominates and annular peaks of stress occur. Recent studies have shown that, in scoliosis, high hydrostatic pressures are seen with asymmetrical stresses from concave to convex sides. These abnormalities could influence both disc and endplate cellular activity directly, causing asymmetrical growth and matrix changes. In addition, disc cells could be influenced via nutritional changes consequent to end-plate calcification. Evidence suggests that the stress environment of the scoliotic disc is abnormal, probably generated by high and asymmetrical loading of non-muscular origin. If present in the scoliotic spine during daily activities, this could generate a positive feedback of cellular changes, resulting in curve progression. Future advances in understanding may rely on the development of computer models owing to the difficulties of in-vivo invasive measurements.

Motor neuron involvement in experimental lumbar nerve root compression: a light and electron microscopic study.

Study Design. The aim of this study is to investigate changes in lumbar motor neurons induced by mechanical nerve root compression using an in vivo model. This study is to investigate the changes of lumbar motor neuron induced by mechanical nerve root compression using in vivo model. Objectives. The effect of axonal flow disturbance induced by nerve root compression was determined in lumbar motor neuron. Summary of Background Data. The lumbar motor neuron should not be overlooked when considering the mechanism of weakness, so it is important to understand the morphologic and functional changes that occur in motor neurons of the spinal cord as a result of nerve root compression. However, few studies have looked at changes of neurons within the caused by disturbance of axonal flow, the axon reaction, chromatolysis, and cell death as a result of mechanical compression of the ventral root. Methods. In mongrel dogs, the seventh lumbar nerve root was compressed for 1 week, or 3 weeks using a clip. Morphologic changes of the motor neurons secondary to the axon reaction were examined by light and electron microscopy. Results. Light and electron microscopy showed central chromatolysis of motor neurons in the lumbar cord from 1 week after the start of compression. After 3 weeks, some neurons undergoing apoptosis were seen in the ventral horn. Conclusion. It is important to be aware that, in patients with nerve root compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction is not confined to degeneration at the site of compression but also extends to the motor neurons within the lumbar cord as a result of the axon reaction. Patients with weakness of lower leg should therefore be fully informed of the fact that these symptoms will not resolve immediately after surgery.

Fine structure of cartilage canal and vascular buds in the rabbit vertebral endplate. Laboratory investigation.

OBJECT The vascular terminations (vascular buds) in the bone-disc junction area are structurally very similar to cartilage. In all previous studies to date, however, the roles of cartilage canals and vascular buds were mainly discussed using histological and transparent sections but not electron microscopic sections. The purpose of this study was to clarify the ultrastructure of the vascular bud seen in the bone-disc junction in comparison to the cartilage canal. METHODS Japanese white rabbits from 2 days to 6 months of age were used in this study. The bone-disc junctions were examined by microangiogram and light and electron microscopy, and morphological changes and their association with the age of the animals were noted. RESULTS The fine structure of the vascular bud was similar to that of the cartilage canal that nourished the growing cartilage. They were composed of arteries, veins, capillaries, cells resembling fibroblasts, and macrophages. The capillaries in the cartilage canal were all the fenestrated type. Vascular buds were seen over the entire bone-cartilage interface, with maximum density in the area related to the nucleus pulposus. They projected into the bone-disc junction area from the vertebral body contacting the cartilaginous endplate directly. CONCLUSIONS The results of this study clarify the formation process and ultrastructure of the vascular bud seen in the bone-disc junction. The authors found a strong structural resemblance between the vascular bud and the cartilage canal and hypothesize that the immature cells seen surrounding the cartilage canal and vascular bud represent a common precursor for the 3 main types of connective tissue cells seen during early vertebral development.

Lidocaine cytotoxicity to the zygapophysial joints in rabbits: changes in cell viability and proteoglycan metabolism in vitro.

Study Design. To examine whether lidocaine cytotoxicity to chondrocytes has been implicated in the development of osteoarthritis of the zygapophysial joints. Objective. This study was performed to determine the effects of varying concentrations and exposure times of lidocaine on the viability and proteoglycan metabolism of rabbit zygapophysial chondrocytes in vitro. Summary of Background Data. Zygapophysial joint injections are commonly administered with lidocaine for chronic spinal pain in orthopedic treatment. A lot of studies on the effect of zygapophysial joint injections are clinical, but many questions on the effect of lidocaine to zygapophysial chondrocytes remain unanswered. Methods. Cartilage was obtained from zygapophysial joints of adult rabbits. Chondrocytes in alginate beads were cultured in medium containing 6% fetal calf serum at 370 mOsmol at cell densities of 4 million cells/mL. They were then cultured for 24 hours under 21% oxygen with 0.125%, 0.25%, 0.5%, and 1% lidocaine, and without lidocaine as control. The cell viability profile across intact beads was determined by manual counting using fluorescent probes (LIVE/DEAD assay) and transmission electron microscopy. Lactate production was measured enzymatically as a marker of energy metabolism. Glycosaminoglycan (GAG) accumulation was measured using a modified dimethylmethylene blue assay. Results. Cell viability decreased in a time- and dose-dependent manner in the concentration range of 0.125% to 1.0% lidocaine under the confocal microscope. Under the electron microscope, apoptosis increased as the concentration of lidocaine increased. GAG accumulation/tissue volume decreases as the concentration of lidocaine increased. However, GAG produced per million cells and the rate of lactate production per live cell was significantly higher for cells cultured at 0.5% and 1% lidocaine than the control group. Conclusion. While these in vitro results cannot be directly extrapolated to the clinical setting, this data suggestcaution in prolonged exposure of zygapophysial cartilage to high concentration lidocaine.

Microvascular system of the lumbar dorsal root ganglia in rats. Part I: a 3D analysis with scanning electron microscopy of vascular corrosion casts

OBJECT So far, the morphological features of the vascular system supplying the dorsal root ganglion (DRG) have been inferred only from microangiograms. However, in the past most of these studies lacked 3D observations. This study presents the details of the microvasculature of the lumbar DRG visualized by scanning electron microscopy of vascular corrosion casts. METHODS Wistar rats were anesthetized with intraperitoneal sodium pentobarbital. After thoracotomy, the vascular system was perfused with heparinized saline, and Mercox resin was injected into the thoracic aorta. After polymerization of the resin, the vascular casts were macerated with potassium hydroxide, washed with water, and dried. The casts were examined with a scanning electron microscope. RESULTS The vascular cast of the DRG was observed to have a higher density of vessels than the nerve root. Bifurcation or anastomoses of capillaries took place at approximately right angles, in a T-shaped pattern. Within the DRG, both the arterial supply and the capillary network contained blood flow control structures (ring-shaped constrictions in the cast probably representing a vascular sphincter in the microvessel). Three types of vessels could be distinguished: tortuous, straight, and bead-like capillaries. The dilations, bulges, and tortuousness of capillaries could serve the function of locally increasing the capillary surface area in a sensory neuron. CONCLUSIONS The results of this study suggest a causal relationship between the metabolic demands of local neuronal activity and both the density of the capillary network and the placement of the blood flow control structures.

Microvascular system of the lumbar dorsal root ganglia in rats. Part II: neurogenic control of intraganglionic blood flow

OBJECT The dorsal root ganglion (DRG) should not be overlooked when considering the mechanism of low-back pain and sciatica, so it is important to understand the morphological features of the vascular system supplying the DRG. However, the neurogenic control of intraganglionic blood flow has received little attention in the past. The authors used an immunohistochemical technique to investigate the presence and distribution of autonomic and sensory nerves in blood vessels of the DRG. METHODS Ten Wistar rats were used. To investigate the mechanism of vasomotion on the lumbar DRG, the authors used immunohistochemical methods. Sections were incubated overnight with antisera to tyrosine hydroxylase (TH), aromatic L-amino-acid decarboxylase (AADC), 5-hydroxytryptamine, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SOM), neuropeptide Y (NPY), leucine-enkephalin, and cholineacetyl transferase (Ch-E). The avidin-biotin complex method was used as the immunohistochemical procedure, and the sections were observed under a light microscope. RESULTS In the immunohistochemical study, TH-, AADC-, SP-, CGRP-, VIP-, SOM-, NPY-, and Ch-E-positive fibers were seen within the walls of blood vessels in the DRG. This study revealed the existence of a comprehensive perivascular adrenergic, cholinergic, and peptidergic innervation of intraganglionic blood vessels, with a possible role in neurogenic regulation (autoregulation) of intraganglionic circulation. CONCLUSIONS The presence of perivascular nerve plexuses around intraganglionic microvessels suggests that autonomic nerves play an important role in intraganglionic circulation.

A Case of Nerve Root Heat Injury Induced by Percutaneous Laser Disc Decompression Performed at an Outside Institution: Technical Case Report

OBJECTIVE In recent years, percutaneous laser disc decompression (PLDD) has become a routine surgical procedure because it can be performed under local anesthesia and is minimally invasive. However, there is a risk of nerve root and endplate injury owing to heat generated by laser irradiation during PLDD. We recently performed salvage surgery on a patient with heat injury to the L5 nerve root that developed after PLDD. CLINICAL PRESENTATION One month before presenting to our hospital, the patient underwent two sessions of PLDD for lumbar vertebral disk herniation at another institution. The patient developed worsening sciatica, as well as bowel and urinary problems after the PLDD. INTERVENTION We performed salvage surgery after PLDD. The intraoperative findings in the present case included carbon spots in the dura mater of the nerve root and a disc herniation strongly adherent to the nerve roots. These findings indicate that the area adjacent to the nerve roots was damaged by excessive heat during laser irradiation. CONCLUSION When salvage surgery is performed after a PLDD procedure, disc and nerve root injuries owing to laser heat energy must be considered.