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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes the neuropathology of progressive axonopathy (PA), an autosomal recessive inherited neuropathy of Boxer dogs, which affects CNS and PNS. The nerve roots contain numerous myelin bubbles and proximal paranodal axonal swellings containing vesicles, vesiculo-tubular profiles and disorganized neurofilaments. The myelin sheath overlying such swellings is often attenuated. As the disease develops there are progressive changes in the myelin sheath with thinning at paranodal and internodal locations, loss of myelin from lengths of axon and the formation of short internodes with disproportionately thin sheaths. The abnormalities show a very definite selectivity for nerve roots and proximal nerves. Conversely, the frequency of degeneration and regeneration is greater distally except in the cervical ventral roots which contain numerous regenerating clusters. In the CNS numerous axonal spheroids are found in the lateral and ventral columns of the spinal cord and in various brain stem nuclei, particularly the superior olives, accessory cuneate nuclei and lateral lemniscus and its nucleus. Axonal degeneration which occurs mainly in the cord shows no obvious tract or proximal/distal selectivity. The optic pathways are also involved, predominantly adjacent to the chiasma. The autonomic nervous system is affected and distal limb muscles show varying, but usually minor, degrees of neurogenic atrophy. The condition, which has no obvious direct parallel in human or veterinary medicine, shows gross disturbances of axon-glial inter-relationships in both CNS and PNS.
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PMID:Progressive axonopathy: an inherited neuropathy of boxer dogs. 2. The nature and distribution of the pathological changes. 409 48

The pathophysiologic events in optic nerve axons have recently been recognized as crucial to an understanding of clinically significant acquired alterations in the ophthalmoscopic appearance of the optic disc. Stasis and related abnormalities of axonal transport appear to explain most aspects of optic nerve head swelling, including optic disc drusen and retinal cottonwool spots. Loss of axoplasm and axonal death can be invoked to interpret optic disc pallor, thinning and narrowing of rim tissue, changes in the size and outline of the optic cup, laminar dots, atrophy of the retinal nerve fiber layer, and acquired demyelination and myelination of the retinal nerve fiber layer. It is speculated that the axons may also play a role in the mechanical support of the lamina cribrosa in resisting the pressure gradient across the pars scleralis of the optic nerve head. Axons and their associated glial cells may be involved in those cases where "reversibility" of cupping of the optic disc has been reported. The structure, physiology, and experimental pathologic findings of the optic nerve head have been reviewed. Many aspects concerning the final anatomic appearance of the optic nerve head have been explained. However, many questions remain concerning the intermediate mechanisms by which increased intracranial pressure retards the various components of axonal transport in papilledema and by which increased IOP causes axonal loss in glaucoma. Investigation of the molecular biology of axonal constituents and their responses to abnormalities in their physical and chemical milieu could extend our understanding of the events that result from mechanical compression and local ischemia. Moreover, we have identified a need to further explore the role of axons in the pathophysiology of optic disc cupping.
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PMID:Optic nerve axons and acquired alterations in the appearance of the optic disc. 620 9

An experimental study of neuropathy due to 2,5-hexanedione (2,5-HDione) was performed in rats by using simultaneously both electrophysiological and histopathological methods. Seven rats were given subcutaneously five days a week 200 mg/kg of 2,5-HDione for first 3 weeks and then 300 mg/kg for the next 5 weeks. Nerve conduction velocities in the tail were measured every week and after the respective measurement times one animals was sacrificed for histological study. At the 2nd week of the experiment, 2,5-HDione-treated rat showed a slight morphological changes with swollen axons in the posterior spinal root fiber and tail nerve. A slowing of motor and sensory conduction velocity (MCV and SCV) in the tail was observed in the treated group at the 4th week. Weakness of hindlimbs was apparently seen at the 5th week. At the 6th and 7th week, histological changes including giant axonal swelling, fiber loss, thinning of myelin and demyelination, were prominent in the various regions of the peripheral nervous system. Additionally, degenerative changes of the spermatogenic cells, especially the formation of multinucleated giant spermatids, were markedly observed in the treated rats at the 6th and 7th week.
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PMID:[An experimental study on electrophysiological and histopathological changes in 2,5-hexanedione-intoxicated rats]. 630 13

Studies using the Golgi method were performed on neocortical and cerebellar tissues from a 9-month-old cat with a history of progressive neurological deterioration and a subsequently demonstrated deficiency of the lysosomal enzyme alpha-D-mannosidase in both neural and non-neural tissues. Many cortical pyramidal neurons demonstrated morphological alterations involving formation of abnormal enlargements (meganeurites) at the axon hillock-initial segment area, abnormal sprouting of neurites (secondary neurites) in this same region, and various types of dendritic changes, such as formation of focal enlargements, thinning, and spine loss. Many nonpyramidal neurons also were abnormal but displaced only dendritic changes similar to those seen in pyramidal neurons. Cerebellar Purkinje cells displayed dendritic systems marked by focal swellings and often demonstrated one or more enlargements within axons (axonal spheroids) at some distance from otherwise normal-appearing cell bodies. Feline mannosidosis appears to be another of the lysosomal storage diseases in which highly specialized morphological changes accompany storage of unmetabolized substrate and contribute to the pathogenesis of the disease process.
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PMID:Alterations in neuron morphology in feline mannosidosis. A Golgi study. 721 Dec 1

The effects of high toxic doses of the anticancer drugs, etoposide and its phosphate derivative, BMY-40481, on the nervous system of female CD-1 mice were examined by light microscopy (LM) and transmission electron microscopy. Mice were euthanatized 4 wk following a single iv injection of either 0, 50, 100, or 150 mg/kg of BMY-40481 or 44 or 88 mg/kg of etoposide. Mice treated with 100 or 150 mg/kg of BMY-40481 or 88 mg/kg of etoposide had clinical symptomology of progressive ataxia, impaired righting reflex, and splaying and paresis of fore- and hindlimbs at day 8. Similar, dose-related LM changes were observed with both drugs at all doses and consisted of degeneration of dorsal root ganglion cells and axonal degeneration of their distal and proximal processes in peripheral nerves, dorsal spinal roots, and dorsal funiculi of spinal cord. Axonal degeneration was characterized by LM as shrinkage, swelling, and fragmentation of axon cylinders accompanied by secondary demyelination. Degenerative changes in ganglion cell bodies included eccentric nuclei, cytoplasmic vacuolation, central chromatolysis, and peripheral clumping of Nissl's bodies. Ultrastructurally, ganglion cell bodies had focally extensive dilation of the rough endoplasmic reticulum, mitochondrial swelling, increased numbers of phagolysosomes and prominent aggregations of microfilaments (globular filamentous bodies). Ultrastructural axonal changes occurred primarily in large, myelinated fibers and consisted of axonal swelling or loss, thinning of myelin sheaths, and a decrease in the number of organelles. This is the first report of etoposide-related sensory neuropathy in laboratory rats, a model that my be useful for the study of etoposide-related peripheral neuropathy in humans.
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PMID:Etoposide- and BMY-40481-induced sensory neuropathy in mice. 789 82

Traditionally, gamma-diketone neuropathy is classified as a distal axonopathy and has been characterized by giant axonal swellings in CNS and PNS tissues. These swellings contain neurofilamentous masses and are associated with thinning and retraction of the myelin sheath. It has been proposed that this axonopathy is caused by direct gamma-diketone modification of neurofilaments (NFs) involving pyrrolation of epsilon-amino groups on NF lysyl residues and possibly secondary autoxidation of the pyrrole rings with creation of covalent NF-NF crosslinks. Neurofilaments are thought to undergo chemical modification as they progress along the axonal axis and, eventually, accumulate at distal nodes of Ranvier where their proximodistal movement is impeded. Development of swelling presumably initiates axonal degeneration and subsequent functional deficits. However, other research suggests that axonal swellings are a non-specific effect related to subchronic gamma-diketone exposure. Such evidence draws into question the mechanistic relevance of these swellings. In contrast, research conducted over the past decade indicates axonal atrophy is a specific morphologic component of gamma-diketone neuropathy which might have both functional and mechanistic importance. In this overview, the potential neurotoxicological significance of both axonal swellings and atrophy are evaluated critically. Based on the evidence to be presented, we propose that axonal atrophy is the morphological consequence of the molecular mechanism of gamma-diketone neuropathy. Accordingly, several mechanistic scenarios related to the development of atrophy will be discussed. It is hoped that this Forum will stimulate scientific debate and initiate laboratory investigations which will either confirm or refute the involvement of axonal atrophy in gamma-diketone neurotoxicity. Investigating gamma-diketone atrophy might provide insight into the mechanism of other toxic axonopathies which are also associated with reduced axon caliber; e.g., acrylamide and carbon disulfide neuropathies.
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PMID:The relevance of axonal swellings and atrophy to gamma-diketone neurotoxicity: a forum position paper. 921 85

The corpus callosum results from neocortical commissural axon fasciculation. Its development reflects the interhemispheric circuitry and then follows the successive steps of synaptogenesis. The first stage consists of callosal neuron differentiation, which allows the extention of the future callosal axon; this is an early event that occurs while neuronal migration to the cortical plate is still ongoing. Callosal axon guidance towards its specific target is the second step which includes reaching and crossing the midline and further target recognition with formation of initial synapses. This period extends from 12 to 22 post-conceptional weeks and corresponds to the following histological features: i) progressive invasion by callosal growth cones of the dorsal part of lamina reuniens through a preformed glial pathway; ii) appearence of the three parts of corpus callosum, namely truncus, rostrum and lastly the splenium. Both these stages are genetically controlled either directly by developmental gene expression (neurogenesis genes) or indirectly by the establishment of cue maps (spatial expression of extra-cellular matrix proteins). The third step is that of synapse remodeling by synaptic activity, giving rise to axonal elimination, macroscopically revealed by a transitory thinning of corpus callosum. This perinatal event contributes to the corpus callosum acquiring a mature topography. Finally, analysis of corpus callosum ontogenesis appears as a striking model of synaptogenesis study and provides physiopathological assumptions for a understanding of the corpus callosum agenesis.
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PMID:[Histogenesis of the corpus callosum]. 975 25

Neural cell adhesion molecules (CAM) play important roles in neural development, neurite outgrowth, axonal guidance, fasciculation and synapse formation. Neuropathological studies of X-linked hydrocephalus (XLH) associated with L1 CAM mutations emphasize marked hypoplasia of the pyramidal tract, agenesis of the corpus callosum and septum pellucidum, and a thin cerebral mantle with hypoplastic white matter, but there are no detailed studies of the cerebral cortex in the literature. We report clinical, neuroimaging, and neuropathological findings in three boys with XLH. All had severe congenital hydrocephalus with marked thinning of the cerebral mantle and severe development disabilities. The brain specimens from the three boys showed both pachygyria and polymicrogyria, hypoplasia of the medullary pyramids, hypoplasia of the corpus callosum, small anterior commissure, hypoplasia and poorly differentiated hippocampi. A small but patent aqueduct was present in all three brains. Despite the extensive cerebral malformations, the cortex in all three brains showed normal-appearing laminar cortical neuronal architecture and absence of gliosis. In XLH, it is likely that the poor developmental outcome of spasticity, contractures and severe mental retardation results from a disturbance of neuronal connectivity, fasciculation, and synapse formation rather than aqueductal stenosis, increased intracranial pressure, or abnormal neuroblast migration.
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PMID:The pachygyria-polymicrogyria spectrum of cortical dysplasia in X-linked hydrocephalus. 992 16

An ultrastructural study of rat hippocampus was performed on young (group 1) and old (group 4) rats receiving daily subcutaneous injections of aluminum L-glutamate and on old untreated rats (group 5). Young controls were treated with sodium L-glutamate (group 2) and physiological saline (group 3). Group 1 showed vacuolated astrocytes with numerous lipofuscin deposits, mitochondrial swelling, a thinning of the myelin sheath, and many multivesicular bodies invading the cytoplasm. Cellular structure did not appear to be affected in groups 2 and 3. Group 4 showed swollen mitochondria, a demyelination process in axonal regions, sizable perivascular oedema with vessel retraction and gliofilament bundles. In this group, lipofuscin deposits in astrocytes were associated with multivesicular bodies that thinned the myelin sheath to the breaking point; however, no excitotoxic glutamate-induced effects were observed. In group 5, extreme cytoplasmic vacuolation was observed, with massive mitochondrial swelling, considerable thinning of the myelin sheath (at times to the breaking point), sizable vacuolar degeneration and gliofilament bundles. These results indicate that ultrastructural alterations in the hippocampus, such as cell vacuolization, massive mitochondrial swelling and the demyelination process, occur with aging and independently of aluminum intoxication. Similar alterations were observed in aluminum L-glutamate-intoxicated young rats, but not in controls. These results are consistent with aluminum-induced acceleration of the aging process.
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PMID:Ultrastructural study of rat hippocampus after chronic administration of aluminum L-glutamate: an acceleration of the aging process. 1122 39

Sensory innervation of the skin subserves protective sensations for the body to prevent thermal and noxious injuries. Neurophysiologically, they belong to the categories of Adelta and C fibers, usually with caliber less than one micro m in diameter. Morphological demonstration of the terminals of these nerves in the epidermis has been recognized recently by sensitive immunocytochemistry and an axonal marker, the protein gene product 9.5 (PGP). PGP is a ubiquitin C-terminal hydrolase, which is abundantly present in the nervous system, and particularly enriched in the unmyelinated nerves. Sensory nerves positive for PGP arise from the dorsal root ganglion, pass through the dermis, parallel the epidermis-dermis border, penetrate the basement membrane, move vertically and upwards in the epidermis with tortuous course and knobby appearance, and finally terminate at the granular layers of the epidermis. In rodents, denervation of the skin results in degeneration of epidermal nerves within 48 h of nerve transection, and thinning of the epidermis. In humans, application of this technique to evaluate disorders of the peripheral nervous system makes study of the degeneration of sensory nerve terminals possible. Patients with sensory neuropathy had fewer epidermal nerves than normal subjects, consistent with the notion of distal axonopathy. This approach has the potential to evaluate human sensory neuropathy in temporal and spatial domains. In addition, the influences of epidermal denervation open a new field to explore the interactions between sensory nerves and keratinocytes.
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PMID:Skin Innervation and Its Effects on the Epidermis. 1238 90


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