Morphological Sequelae Research Articles

Reduced tolerance to acute renal ischemia in mice with a targeted disruption of the osteopontin gene

Mice with a targeted disruption of the osteopontin gene through homologous recombination in embryonic stem cells have recently been generated and shown to be characterized by unaltered fertility and normal embryonic and postnatal development, including renal development, but altered osteoclastogenesis from spleen progenitors. The lack of detectable pathological manifestations in kidneys of mice with the targeted disruption of the osteopontin gene (opn -/-) makes them an excellent model for studies of pathophysiological processes that are thought to be accompanied by changes in renal osteopontin expression. It has previously been suggested that osteopontin may play an important role in the pathophysiology of acute renal failure, thus prompting this study. Wild-type and opn -/- mice were subjected to 30 minutes of renal ischemia and were studied 24 hours later. Control opn +/+ mice showed a significant retention of blood urea nitrogen and creatinine, which is indicative of the development of ischemic acute renal dysfunction. This was accompanied by a 2.7-fold increase in the immunodetectable osteopontin compared with sham-operated control. Animals with the disrupted osteopontin gene exhibited ischemia-induced renal dysfunction, which was twice as pronounced as that observed in mice with the intact osteopontin response to stress. In addition, the structural damage to the ischemic kidneys obtained from opn -/- mice was more pronounced than that observed in similarly treated wild-type mice. This was associated with the augmented expression of inducible nitric oxide synthase and the prevalence of nitrotyrosine residues in kidneys from opn -/- mice versus wild-type counterparts. In vitro studies with proximal tubular cells subjected to hypoxia in the presence of OPN, but not OPN with deleted arginine-glycine-aspartic acid (RGD) domain, resulted in cytoprotection. The comparative analysis of functional and morphological sequelae of acute renal ischemia in opn +/+ and opn -/- mice provides strong evidence of renoprotective action of osteopontin in acute ischemia.

The Use of Magnetic Resonance Imaging for Evaluation of Right Ventricular Dysfunction

Radiological techniques to image the right ventricle (RV) are difficult, due to complexities of shape of the RV and its relationship to surrounding structures. During disease states, unpredictable changes in the dimensions and shape of the RV make quantitative analysis by conventional techniques difficult. Magnetic resonance imaging (MRI) allows detailed visualization of the shape and internal morphology of the RV and pulmonary arteries and quantitation of indices of RV function. MRI may be invaluable to assess morphological sequelae of congenital cardiovascular malformations and secondary causes of pulmonary hypertension. Recent studies utilizing MRI to diagnose pulmonary thromboembolism are promising. The indications for MRI for pulmonary and cardiovascular conditions continue to evolve. MRI may be a useful, noninvasive adjunct for evaluating suspected right ventricular dysfunction for a host of cardiac and pulmonary disorders.

Focal glomerulosclerosis in the remnant kidney model--an inflammatory disease mediated by cytokines.

The mechanism of progression of established renal disease remains unclear. While a low protein diet slows this progression, the role of cytokines in this process has been little investigated. We investigated cytokine expression by Northern blot and immunohistochemistry in two groups of 5/6 nephrectomized rats (5/6 Nx) fed a normal (24%) or low (6%) protein diet and compared them with sham operated controls. The rats on 6% protein diet had significantly less focal glomerulosclerosis (FGS) (17.4 +/- 4.4 vs 27.4 +/- 8.8%, P < 0.05) and global sclerosis (GGS) after 7 weeks (0.4 +/- 0.8 vs 3.5 +/- 2.1% of glomeruli P < 0.05). Both experimental groups showed three times control levels of MCP-I expression after 2 weeks. However in the 5/6 Nx 6% protein group the expression decreased at 4 weeks (1.5 times controls) and reached control levels after 7 weeks. In contrast, the 5/6 Nx 24% protein group exhibited a further marked increase after 4 weeks (5.6 times controls) and was still two-fold higher after 7 weeks. TGF-beta expression was modestly but consistently increased at all time points (120-160% of controls), with no difference between the two study groups. Neither IL-1 beta or TNF-alpha was detectable at any time. Immunohistochemistry demonstrated TGF-beta intracellularly in distal tubular cells in both experimental and control animals, while MCP-1 protein was found in the area of FGS and in the apical pole of distal tubular cells in both experimental groups. Glomerular and interstitial ED1 positive cells were significantly increased after four weeks in the 5/6 Nx 24% protein group (P < 0.05). A 'mechanical' injury to the kidney clearly results in an inflammatory response associated with the upregulation of MCP-1. A low protein diet modulates the expression of MCP-1 and improves the morphological sequelae seen after renal ablation.

Cerebroprotective effects of a novel pyrazoline derivative, MS-153, on focal ischemia in rats.

MS-153 ((R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline) is a novel pyrazoline compound that has potent cerebroprotective effects in the rat focal cerebral ischemia model. Middle cerebral artery (MCA) occlusion in rats allows detailed assessment of both functional and morphological sequelae of brain infarct. Using this model, we evaluated the cerebroprotective effects of MS-153. Treatment with MS-153 (12.5 mg/kg, i.v. bolus followed by 6.25 mg/kg/hr or 25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 7 days) significantly reduced infarct volumes and improved neurological deficits in MCA occluded rats 7 days after occlusion. Delayed treatment significantly reduced infarct volume 24 hr after MCA occlusion when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 21 hr) administration was started 3 hr after occlusion. Brain edema was also significantly improved when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 18 hr) administration was started 6 hr after occlusion.

Cerebroprotective Effects of a Novel Pyrazoline Derivative, MS-153, on Focal Ischemia in Rats

MS-153 ((R)-( — )-5-methyl-l-nicotinoyl-2-pyrazoline) is a novel pyrazoline compound that has potent cerebroprotective effects in the rat focal cerebral ischemia model. Middle cerebral artery (MCA) occlusion in rats allows detailed assessment of both functional and morphological sequelae of brain infarct. Using this model, we evaluated the cerebroprotective effects of MS-153. Treatment with MS-153 (12.5 mg/kg, i.v. bolus followed by 6.25 mg/kg/hr or 25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 7 days) significantly reduced infarct volumes and improved neurological deficits in MCA occluded rats 7 days after occlusion. Delayed treatment significantly reduced infarct volume 24 hr after MCA occlusion when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 21 hr) administration was started 3 hr after occlusion. Brain edema was also significantly improved when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr infusion for 18 hr) administration was started 6 hr after occlusion.

Vascular changes in the cerebral cortex in HIV-1 infection. II. An immunohistochemical and lectinhistochemical investigation.

In human immunodeficiency virus 1 (HIV-1)-infected patients, a hypoperfusion is seen by SPECT analyses in different brain regions but a specific pattern for the predominance of a specific brain region has not been found. The vessels of the cerebral cortex of the frontal, temporal, parietal, and occipital lobes of acquired immunodeficiency syndrome (AIDS) brains and control brains were analyzed by immunohistochemistry and lectin histochemistry. Immunohistochemistry was performed for collagen IV, laminin (basal lamina), and factor VIII (endothelial cell) and lectin histochemistry [Ricinus communis agglutinin (RCA-I), Ulex europaeus agglutinin (UEA-I), wheatgerm agglutinin (WGA) and soybean agglutinin (SBA)] was used to study changes of glycoproteins in the endothelial cell membrane. Vessels were counted in the gray and white matter, and their staining intensity for the different antibodies and lectins was rated using a three-point scale. Immunoreactivity for collagen IV was reduced in AIDS brains, which may be related to thinning of the basal lamina of cerebral vessels, as has previously been shown by electron microscopy. Lectin histochemistry with SBA, UEA-I and WGA indicated loss of glycoproteins in the membrane of endothelial cells. The data from the present study show morphological changes of the endothelial cells and of the basal lamina in the brain of individuals with AIDS, and might represent the morphological sequelae of a disturbed blood-brain barrier, or may account for the hypoperfusion seen in SPECT analyses.

Memantine reduces functional and morphological consequences induced by global ischemia in rats

In this study the effect of memantine, an antagonist at the N-methyl- d-aspartate receptor, on spatial learning deficit and on neuronal damage following transient: cerebral ischemia was evaluated. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. Memantine was administered 20 min before induction of ischemia at a dose of 10 or 20 mg/kg. One week after surgery spatial learning was tested in the Morris water maze. Treatment with the higher dose of memantine reduced the increase in escape latency and in swim distance induced by 4VO. Neuronal damage in the CA1 sector of the hippocampus and in the striatum produced by 4VO was significantly attenuated by 20 mg/kg memantine. Treatment with the lower dose of memantine bad no influence on the deficit in spatial learning and the neuronal damage resulting from ischemia. The present data demonstrate that treatment with a neuroprotective agent like memantine can reduce functional as well as morphological sequelae induced by ischemia.

Morphological fate and sequelae of human atherosclerosis: Evaluation of immune mechanisms in atherogenesis through immunohistological and ultrastructural analysis

Modern techniques of investigation have revealed several similarities between atherosclerosis and chronic inflammation, and that immune mechanisms seem to operate in the incipient and subsequent phases of atherosclerosis. In the present study, the fate and morphogenesis of human atherosclerosis was considered, and the immune aspects of atherogenesis were analysed, using fresh human aorta obtained from autopsy cases. One of the earliest changes in the grossly normal, lesion-prone area of the aorta from young cases (prelesional changes) was the infiltration of blood-borne T lymphocytes and monocytes/macrophages beneath the endothelium. Cell-populated lesions abounding in T lymphocytes and macrophages, often bearing signs of activation, with or without cytoplasmic lipids were found in the fatty streaks, cap and shoulder regions of more advanced atheromatous plaques. The ultrastructural observation of cell-rich areas suggested that cognate cell-to-cell interaction plays a pivotal role in atherosclerosis, as well as cytokine-mediated paracrine or autocrine mechanisms. From an immunological perspective, the areas where both cell types are especially numerous and in close proximity are considered to be the areas with an index of disease activeness or progressiveness. Also, the present authors show evidence of clonal expansion of T lymphocytes. It is most likely that the increase of intimal cells was caused by the recruitment of immunocompetent cells from the blood-stream into the intima and by the clonal expansion of T lymphocytes. In addition, dead or dying cells were identified in areas of different stages ranging from prelesional areas to atheromatous plaques. Thus, the initiation and progression of human atherosclerosis appears to be punctuated by brief episodes of immunological events related to cell infiltration, proliferation and death.

Remyelination of mouse spinal cord axons demyelinated by local injection of lysolecithin.

Local injections of lysolecithin are commonly used to produce areas of demyelination in the CNS. For the mouse, the demyelinating initial phase of lesion development has been described previously but the spontaneous repair which follows has not. In this study we describe the morphological sequelae which result from the injection of 2 microliters of 1% lysolecithin into the spinal cord of adult mice. Lesion length was variable, extending 8 mm or more in 33% of lesioned animals. By 7 days after injection very little extracellular myelin debris was detected and remyelination had commenced. Remyelination progressed rapidly so that almost all axons were invested by myelin sheaths by 23 days. Remyelination was accompanied by a prominent astrocytosis. The long lesion length and the rapidity of repair has important implications for studies designed to assess the ability of transplanted myelinogenic cells to migrate towards demyelinating lesions.

Callitrichid IgM-nephropathy--an old age-related disease?

In 185 callitrichids of exactly known age the occurrence of mesangial IgM-deposits and mesangial lesions has been evaluated. Mesangial IgM-deposits were observed already in early infancy, at that time without morphological sequelae. Signs of mesangial lesions were first observed in a 3-months old animal and with a sharp increase of mesangial lesions between 4 months and one year of age all suggesting an onset early in life. In contrast in higher age groups a significant number of animals suffered from glomerulosclerosis without IgM deposits, which could be interpreted as 'old age nephropathy' independent from IgM-nephropathy.

The Role of Pressure on Regulation of Craniofacial Bone Growth

The regulatory role of pressure on growth and differentiation of the craniofacial skeleton is largely unknown. We devised an experimental model to determine if the graded application of pressure could exert a trophic influence on craniofacial bone, allowing deliberate alteration and reshaping of the facial skeleton. To examine this question, 18 kittens were used to determine the adverse morphological sequelae after orbital evisceration and to compare the ability to remedy such facial deformity with the use of an inert implant or pressure-induced tissue expansion. In addition to detailed craniometric measurements of the cranial, orbital, and midfacial regions, histological analyses as well as radiographic and gross morphological comparisons were evaluated. Our results demonstrate a severe asymmetry and constriction in the orbital and midfacial regions resulting from orbital evisceration in the growing kitten. Placement of an inert implant will help to ameliorate only some of these adverse sequelae, whereas graded application of pressure appears to direct craniofacial bone growth, resulting in normal bony histology and improved facial form. We affirm that regional growth disturbances can alter normal facial development and that the regulatory role of pressure on bone growth can be exploited to dynamically correct abnormal craniofacial anatomy.

Effects of target depletion on adult mammalian central neurons: Morphological correlates

The morphological sequelae induced by target removal were studied on adult cat abducens internuclear neurons at both the somata and terminal axon arborization levels. The neuronal target—the medial rectus motoneurons of the oculomotor nucleus—was selectively destroyed by the injection of toxic ricin into the medial rectus muscle. Retrograde labeling with horseradish peroxidase demonstrated the survival of the entire population of abducens internuclear neurons up to one year after target removal. However, soma size was reduced by about 20% three months postlesion and maintained for one year. At the ultrastructural level, a considerable deafferentation of abducens internuclear neurons was observed at short intervals (i.e. 10 days after lesion). Large regions of the plasmalemma appeared devoid of presynaptic boutons but were covered instead by glial processes. The detachment of synaptic endings was selective on abducens internuclear neurons since nearby motoneurons always showed a normal synaptic coverage. By one month, abducens internuclear neurons recovered a normal density of receiving axosomatic synapses. Anterogradely biocytin-labeled axon terminals of abducens internuclear neurons remained in place after the lesion of medial rectus motoneurons, although with a progressive decrease in density. Ultrastructural examination of the oculomotor nucleus 10 days after the lesion revealed numerous empty spaces left by the dead motoneurons. Targetless boutons were observed surrounded by large extracellular gaps, still apposed to remnanls of the postsynaptic membrane or, finally, ensheathed by glial processes. At longer intervals (> one month), the ultrastructure of the oculomotor nucleus was re-established and labeled boutons were observed contacting either unidentified dendrites within the neuropil or the soma and proximal dendrites of the oculomotor internuclear neurons that project to the abducens nucleus. Labeled boutons were never found contacting with the oculomotor internuclear neurons either in control tissue or at short periods after ricin injection. These results indicate that the availability of undamaged neurons close to the lost target motoneurons might support the long-term survival of abducens internuclear neurons. Specifically, the oculomotor internuclear neurons, which likely suffer a partial deafferentation after medial rectus motoneuron loss, constitute a potential new target for the abducens internuclear neurons. The reinnervation of a new target might explain the recovery of synaptic and firing properties of abducens internuclear neurons after medial rectus motoneuron lesion, which occurred with a similar time course, as described in the accompanying paper [de la Cruz R. R. et al. (1994) Neuroscience 58, 81–97.]

Myenteric plexus destruction alters morphology of rat intestine

Background: It has been shown previously that myenteric plexus destruction by benzalkonium chloride (BAC) increased villus height, crypt depth, and muscle thickness, suggesting that these neurons influence intestinal morphology. A nonspecific trophic effect of BAC, intraluminal stasis, and inflammation resulting from the chemical treatment could also be causes for these changes. Our goals were to (1) show that the morphological sequelae of BAC treatment are caused by myenteric plexus removal and not the factors listed above, and (2) determine whether segmental myenteric plexus removal alters morphology elsewhere in the small intestine. Methods: Six groups of rats were studied: control, chemical denervation (3 mmol/L BAC), surgical denervation, intraluminal stasis produced by partial obstruction, chemical inflammation (5% acetic acid), and surgical inflammation (serosa removal only). Tissue for histological study was taken from the treated segment, 15–20 cm proximal to the treated segment, and 5–10 cm distal to the treated segment 28 days after treatment. Results: Chemical and surgical denervation reduced the number of myenteric neurons by 94% and 98%, respectively. Denervation had a direct effect on morphology; it increased villus height, crypt depth, and muscle thickness in the treated and proximal segments, but only muscle thickness was increased in the distal segment. The other treatments had minimal morphological sequelae. Conclusions: Segmental myenteric plexus removal alters the mucosa in the treated and proximal segments but influences muscle thickness throughout the intestine.

Relationship between abnormal somite development and axial skeletal defects in rats following heat exposure.

The effects of in vivo heat exposure on gestation day (GD) 10 rat embryos were evaluated on GD 11 to determine the relationships between morphological sequelae following in vivo and in vitro exposures and between effects detected on GD 11 and those observed in postnatal day (PND) 3 pups. Anesthetized rats were exposed to 42 degrees C in a warm air incubator until their rectal temperatures reached 41 degrees C or until a rectal temperature of 42-42.5 degrees C had been maintained for 5 minutes. Heat-exposed embryos exhibited a significant decrease in growth parameters including head length, somite number, and protein content/embryo versus controls. These changes correlated well with in vitro effects from an earlier study (G.L. Kimmel et al., '93). Among the morphological endpoints which were slightly delayed in development were the caudal neural tube, branchial bars, forelimb and hindlimb. The only effect on the embryos that could not be explained as a transient delay in development induced by heat was the induction of unsegmented somites. Additional embryos were exposed to 42 degrees C for 15-20 min in vitro and examined specifically for unsegmented somites, which were observed in 47% of embryos exposed to 42 degrees C in vivo or in vitro. This phenomenon was observed in somites 9-20, i.e., those that give rise to cervical and thoracic vertebrae and ribs. These results correlated well with the axial skeletal malformations observed in PND 3 pups exposed to the same heat treatment (C.A. Kimmel et al., '93).

5,8,11,14-eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3).

Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.

Repair of coarctation of the aorta in children: postoperative morphology.

To determine the morphologic sequelae after surgical repair of coarctation of the aorta, the authors retrospectively reviewed angiograms and hemodynamic and clinical data on 215 patients who underwent cardiac catheterization after surgical repair of coarctation of the aorta during a 13-year period. Ninety-seven patients (45%) underwent coarctation resection with end-to-end anastomosis; 92 (43%), subclavian-flap angioplasties; and 26 (12%), synthetic-patch repairs. Sixty-four patients (30%) had an "aneurysm," defined as a measurement ratio of repair site to diaphragmatic aorta greater than 1.5. Transverse-arch or isthmic hypoplasia or recoarctation was detected in 86 patients (40%) and was most commonly associated with septal defects or obstruction of the left ventricular outflow tract. Pullback systolic pressure gradients at catheterization were significantly higher (P = .0001) in the patients with transverse-arch hypoplasia and recoarctation than in those with ratios of transverse arch to diaphragmatic aorta greater than 0.9. Significant postoperative arch obstructions can be predicted with measurement ratios on the basis of the diameter of the abdominal aorta.

Das Syndrom der partiellen cholinergen Deafferentierung des kortikalen Mantels - ein Konzept zur Beschreibung des brain-behaviour-relationships bei dementiellen Erkrankungen

The identification of morphological and biochemical changes in neurodegenerative disorders with both common and different patterns of neuropsychological dysfunction may help to define the neurobiological substrate of amnesic and dementing disorders, and, furthermore, will give some insight into the neuronal organisation of memory processes. The concept of "subcortical and cortical dementia" and the "cholinergic hypothesis of memory dysfunction" reflect two different theoretical approaches which relate psychopathological disturbances in Alzheimer's disease, Parkinson's disease, Korsakoff's psychosis and related conditions either to structurally or to chemically defined systems of the brain. In order to overcome limitations arising from this dichotomy of structural and chemical approaches to the brain-behaviour-relationship, the concept of a "syndrome of partial cholinergic deafferentation of the cortical mantle" is suggested in the present paper. This concept is supported by evidence derived from the biochemical, morphological and behavioural sequelae of acute and chronic experimental interference with the cholinergic afferentation of the cortical mantle by the application of neurotoxins, by pharmacological intervention and by neurotransplantation in rat. Regarding the cholinergic projection neurons of the basal forebrain and upper brainstem as components of the reticular activating system, the involvement of the cholinergic afferentation of the cortical mantle in the mediation of memory processes and their dysfunction under the conditions of neurodegenerative disorders can be explained on the basis of the "Hippocampal Memory Indexing Theory" of Teyler and DiScenna.

Injection of tetrodotoxin into the entorhinal cortex suppresses cell firing in the dentate gyrus

Ablation of the entorhinal cortex (EC) of rats induces a reorganization of afferents and dendrites in the denervated dentate gyrus (DG). The signal which triggers these events is unknown, but one candidate is the reduction of granule cell firing which follows the EC lesion. Testing this hypothesis requires eliminating activity in the perforant path without destroying the EC. In the present study, we evaluated whether injecting tetrodotoxin (TTX) into the EC could reduce neuronal activity in the DG to the same extent as EC ablation. Using microelectrode recording techniques, we recorded the activity of single cells in the DG before and up to 8 h after TTX injection. Transmission over the perforant path was monitored before and up to 24 h after TTX injections by stimulating the EC and recording evoked responses in the DG. TTX injections into the EC consistently reduced the firing rate of neurons in the DG by about 80%. Neither firing rate nor temporodentate-evoked responses recovered during the observation period. Saline injections did not alter either physiological measure. The results suggest that the postlesion decreases in neuronal activity in the DG reflect lost synaptic drive rather than an effect dependent upon early degenerative events. Because TTX injection reduces postsynaptic activity to the same extent as does a lesion, the technique can be used to determine whether a loss of afferent drive is sufficient to induce the biochemical and morphological sequelae of denervation.

Effect of dietary fish oil on lung lipid profile and hypoxic pulmonary hypertension.

The effects of dietary polyunsaturated fats on chronic hypoxic pulmonary hypertension were assessed in rats fed fish oil, corn oil, or a lower fat, "high-carbohydrate" diet (regular) beginning 1 mo before the start of hypoxia (0.4 atm, n = 30 for each). Mean pulmonary arterial pressures were lower in the chronically hypoxic rats fed fish oil (19.7 +/- 1.8 mm Hg) than in the rats fed corn oil (25.3 +/- 1.6 mm Hg) or regular diets (27.5 +/- 1.5 mm Hg, P less than 0.05). The fish oil diet increased lung eicosapentaenoic acid 50-fold and depleted lung arachidonic acid 60% (P less than 0.0001 for each). Lung thromboxane B2 and 6-ketoprostaglandin F1 alpha levels were lower, and platelet aggregation, in response to collagen, was reduced in rats fed fish oil. Chronically hypoxic rats fed fish oil had lower mortality rates than the other hypoxic rats. They also had lower blood viscosity, as well as less right ventricular hypertrophy and less peripheral extension of vascular smooth muscle to intra-acinar pulmonary arteries (P less than 0.05 for each). The mechanism by which dietary fish oil decreases pulmonary hypertension and vascular remodeling during chronic hypoxia remains uncertain. The finding that a fish oil diet can reduce the hemodynamic and morphological sequelae of chronic hypoxia may have therapeutic significance.

The Pathogenesis of Cervical Spondylosis

Cervical spondylosis is a generalized disease process affecting all levels of the cervical spine. Cervical spondylosis encompasses a sequence of degenerative changes in the intervertebral discs, osteophytosis of the vertebral bodies, hypertrophy of the facets and laminal arches, and ligamentous and segmental instability. The natural history of cervical spondylosis is associated with the aging process. Senescent and pathologic processes are thus morphologically indistinguishable. Clinical manifestations of cervical spondylosis may arise when morphologic sequelae are superimposed on a developmentally narrow spinal canal. The two clinical syndromes of spondylotic radiculopathy and myelopathy are distinct, yet they may overlap.