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W F Blakemore

Publications and source records attributed to W F Blakemore.

At least 127 records · Page 7Linked to original sources
PubMed1986

The interaction of Schwann cells with CNS axons in regions containing normal astrocytes.

On occasions retinal axons can be myelinated by Schwann cells. In the present experiments cultured autologous Schwann cells were injected into the optic disc of adult cats and the extent of Schwann cell myelination determined. Little if any Schwann cell myelination of retinal ganglion cell axons developed. Schwann cells were also injected into lesions in the cerebral cortex induced by ethidium bromide. In this site some Schwann cell remyelination was detected, but it was restricted to areas next to regions of malacia induced by the injection procedure. It was concluded that astrocyte responses, limit Schwann cell myelination and remyelination in normal tissue by excluding Schwann cells from the CNS compartment, and induce changes in chronically demyelinated and amyelinated axons which may affect myelination.

Animals↗
PubMed1986

Observations on Wallerian degeneration in explant cultures of cat sciatic nerve.

Wallerian degeneration was studied in vitro using explant cultures of cat sciatic nerve. As these cultures contain no macrophages they highlight the responses of Schwann cells to myelin sheath breakdown. Although there were regional variations in the changes observed in these cultures with respect to time, the sequence of events which lead to Schwann cell proliferation and to fragmentation and liberation of myelin debris into the endoneurial space was established. The initial event was rejection of myelin sheaths by Schwann cells. Liberated Schwann cells then proliferated within the basal lamina tube. In nerve fibres containing proliferating Schwann cells, myelin debris passed through breaks in the basal lamina tube into the endoneurial space. Schwann cells also escaped from the basal lamina tube with the myelin debris. Following the loss of the luminal contents the basal lamina tube collapsed and the intratubular Schwann cells formed bands of Büngner. The Schwann cells which migrated into the endoneurial space and subsequently onto the culture dish retained contact with each other. These studies indicate that rejection of myelin internodes by their supporting Schwann cells set in train a series of events in which Schwann cells and degenerating myelin behaved as separate components. Schwann cells were not involved in phagocytosis or degeneration of myelin. We conclude that Schwann cell proliferation in Wallerian degeneration is directed towards re-establishing cellular continuity within the basal lamina tube which is lost when Schwann cells reject their myelin sheaths.

Animals↗
PubMed1985

Dependence of axolemmal differentiation on contact with glial cells in chronically demyelinated lesions of cat spinal cord.

Chronically demyelinated lesions of cat dorsal columns were created by focal injection of the glial toxin ethidium bromide. Freeze-fracture studies show that the center of the lesion, which is devoid of glial cells and processes, contains axons having neither node-like nor paranodal-type membrane specializations. Near the margin of the lesion, however, where axons are in contact with glial cells, the axolemma sometimes displays focal accumulations of E- and P-face particles resembling those at nodes of Ranvier. In cases where the adjacent cell could be identified, it had the characteristics of an astrocyte. Linear indentations of the axolemma displaying a paracrystalline pattern like that of the paranodal axolemma also occur in the marginal region. Here, the adjacent cell had the characteristics of an oligodendrocyte. These specializations may be closely associated with each other or spatially separate. Normal nodal and paranodal specializations were absent throughout the lesion at all time periods examined. These findings support the view that both the formation and the maintenance of nodal and paranodal axon membrane specializations require contact with glial cells.

Animals↗
PubMed1985

The use of cultured autologous Schwann cells to remyelinate areas of persistent demyelination in the central nervous system.

Areas of persistent demyelination were created in the dorsal columns of the cat spinal cord by injecting ethidium bromide into white matter which had previously been exposed to 40 Grays of X-irradiation. In the centre of such lesions demyelinated axons occurred in a glial-free area while axons next to normal tissue were separated by astrocyte processes. No remyelination occurs in such lesions (Blakemore 1984). Autologous Schwann cells and fibroblasts cultured from a peripheral nerve biopsy were injected into such lesions and the extent of Schwann cell remyelination examined. Only lesions injected with viable cells showed remyelination by Schwann cells; in no lesion were all the demyelinated axons remyelinated. Three forms of association of Schwann cell with axons were detected. In the centre of the lesions Schwann cells either remyelinated axons around or near to blood vessels, or lay next to demyelinated axons and did not form myelin. Schwann cell remyelination was also detected in the astrocyte-containing areas around the edges of some lesions. It was concluded that the extent of Schwann cell remyelination was influenced by the mode of entry of the cells into the lesion and by the architecture of the lesion. The presence or absence of stable extracellular matrix is believed to be the prime factor which influenced Schwann cell remyelination. The relevance of these observations to artificial repair of the lesions of multiple sclerosis is discussed.

Animals↗
PubMed1984

The enzymic defect and storage products in canine fucosidosis.

A marked deficiency of alpha-L-fucosidase and the accumulation of fucose-containing glycoasparagines were found in the brains of two English Springer spaniels suffering from a progressive nervous disorder. Both forms of alpha-L-fucosidase in normal brain, which are separable by ion-exchange chromatography, are absent from the affected animals. The storage products were characterized by t.l.c., gel filtration, g.l.c. and fast-atom-bombardment mass spectrometry. The postulated structures of the main components are: (formula; see text) The enzymic defect and nature of storage products justify designation of this disorder as canine fucosidosis.

Animals↗
PubMed1984

Structural specializations in cat of chronically demyelinated spinal cord axons as seen in freeze-fracture replicas.

Axons in chronically demyelinated spinal cord lesions, induced by ethidium bromide injection, display patches of intramembranous particles and indentations resembling nodal and paranodal axolemmal specializations respectively. Both occur in the marginal region of the lesions where the demyelinated axons are intimately associated with astrocytic and oligodendrocytic processes, and probably correspond to the aberrant node-like and paranodal junctional complexes seen in thin sections of this region. Demyelinated axons in the center of the lesion, which are not in contact with glial processes, do not display these membrane specializations.

Animals↗
PubMed1984

Limited remyelination of CNS axons by Schwann cells transplanted into the sub-arachnoid space.

Areas of primary demyelination which did not subsequently remyelinate spontaneously were prepared in the cat spinal cord by injecting small volumes of ethidium bromide into tissue which had previously been exposed to 40 Grays of X-irradiation. Autologous peripheral nerve tissue was placed in the sub-arachnoid space over such lesions, either at the time of injecting ethidium bromide, or at 14 days or 28 days after injecting ethidium bromide. The extent of Schwann cell remyelination was assessed 28 days after transplantation. In no case were all the demyelinated axons remyelinated; rather, remyelination was limited to axons near to blood vessels. It was concluded that Schwann cells migrated from the transplanted tissue into the lesion via the perivascular space and that they failed to remyelinate the bulk of demyelinated axons because of an absence within the CNS of suitable extracellular matrix.

Animals↗
PubMed1984

The response of oligodendrocytes to chemical injury.

Oligodendrocytes establish relationships with axons at myelination which commit the cell to make and then maintain certain volumes of myelin. As a result of this oligodendrocytes are a heterogenous population of cells. At one extreme, large cells support a single internode on large diameter axons while at the other, small cells support many internodes on small diameter axons. Although it is common practice to separate chemicals which cause vacuolation of myelin sheaths from those which bring about cell death and thus demyelination, many compounds produce vacuolation and/or cell degeneration depending on concentration; an observation which suggests that myelin sheath-associated vacuolation reflects oligodendrocyte toxicity rather than a specific myelinopathy. The restoration of myelin sheath-axon relationships following chemically induced demyelination requires a complex sequence of cell-cell interactions to occur in an orderly manner if new myelin sheaths are to be formed. Recruitment of new oligodendrocytes can be separated from the interaction of oligodendrocytes with axons which results in the laying down of a myelin sheath. The latter event can only take place in the absence of demyelinating agents and in the presence of astrocytes.

6-Aminonicotinamide↗
PubMed1983

The catabolism of mammalian glycoproteins. Comparison of the storage products in bovine, feline and human mannosidosis.

Analysis of the neutral urinary oligosaccharides in bovine, feline and human mannosidosis by thin-layer and gel-permeation chromatography has shown that the patterns of stored oligosaccharides in the three species are different. In bovine and feline mannosidosis the most abundant urinary oligosaccharide is also the most abundant in the tissues of each species. The predominant oligosaccharides were purified by a combination of gel-filtration, ion-exchange and thin-layer chromatography and shown to contain only mannose and N-acetylglucosamine by g.l.c. and g.l.c.--mass spectrometry. The probable composition and size of each oligosaccharide were predicted from its chromatographic properties, sugar composition and the known structure of asparagine-linked oligosaccharides. The bovine and feline oligosaccharides belonged to a homologous series of general composition Mann (GlcNAc)2, whereas the human oligosaccharides belong to a different series, MannGlcNAc. These structures suggest that lysosomal endohexosaminidase is not present in bovine and feline tissues. The predominant feline storage product, Man3(GlcNAc)2, was the expected storage product from the catabolism of complex asparagine-linked glycans. In contrast, the predominant bovine oligosaccharide, Man2(GlcNAc)2, probably lacks one of the alpha-linked mannose residues in the core region. A similar situation occurs in human mannosidosis. It is predicted that in these species either that the residual mutant alpha-D-mannosidase retains activity towards one of the core alpha-linked mannose residues or that another form of lysosomal alpha-D-mannosidase that is unaffected in these disorders occurs. It is concluded that the differences in storage products are due to differences in the catabolic pathways of glycoproteins among the species.

Animals↗
PubMed1983

Node-like axonal specializations along demyelinated central nerve fibres: ultrastructural observations.

Ultrastructural examination of long-term (1 month to 1 year) demyelinated axons of the central nervous system (CNS) has revealed the presence of certain features typical of nerve fibres at the node of Ranvier. Focal regions of dense undercoating of the axolemma were observed and these always extended along regions which were intimately associated with the processes of glial cells. In many cases the glial cells were astrocytes, but in some cases the cells resembled Schwann cells. The astrocytic and Schwann cell processes were sometimes finger-like and they thus resembled the normal projections of these cells onto the nodal axolemma of central and peripheral nerve fibres, respectively. Since the undercoated regions which were associated with astrocytic processes were also often remote from any oligodendrocyte or Schwann cell processes, it seems that certain node-like specializations may form or be sustained in the absence of myelin-forming cells.

Animals↗
PubMed1982

Delayed infarction of spinal cord white matter following x-irradiation.

The thoraco-lumbar spinal cord of 4 cats were subjected to 4000 RADS of X-irradiation. Between 3 and 5 mth afterwards the animals developed weakness of the hind-legs and became uncoordinated. Small infarcts were found in the white matter of the irradiated area of spinal cord, accompanied by neuronal death and oedema of the grey matter close to the central canal. Ultrastructurally the infarcts were shown to stem from necrosis and thrombosis of small blood vessels. Comparison is made with the pathogenesis of spinal cord infarction that occurs in decompression sickness.

Animals↗
PubMed1982

Internodal myelin volume and axon surface area. A relationship determining myelin thickness?

Internodes from normal, remyelinated and regenerated nerve fibres have been isolated from rat spinal roots and sciatic nerve. The internodes have been examined quantitatively by light and electron microscopy to determine their internodal length, myelin thickness, and the circumference and cross-sectional area of both the axons and fibre. Comparison of these measurements of the axon and myelin sheath has revealed a close relationship between the volume of myelin comprising the internode and the area over which the Schwann cell and axon are in close proximity, i.e. the surface area of the axolemma beneath the internodal myelin sheath. The same relationship described not only the internodes on normal nerve fibres, where internodal length is proportional to axon diameter, but also the short and thinly myelinated internodes formed in the adult animal on remyelinated and on regenerated axons. Examination of data presented by Berthold (1978) revealed that a closely similar relationship is also present in feline nerve fibres. In view of the constancy of the relationship between such different types of internode it is suggested that the regulation of myelin volume, and thereby of myelin thickness, may be mediated via the area of the axolemma or of the Schwann cell membrane beneath the myelin sheath.

Animals↗
PubMed1981

Alterations in neuron morphology in feline mannosidosis. A Golgi study.

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.

Animals↗
PubMed1981

Quantitative examination of internodal length of remyelinated nerve fibres in the central nervous system.

The internodal length of remyelinated internodes was examined by observations on teased CNS nerve fibres following primary demyelination induced by intraspinal injections of lysolecithin into the white matter of cats. A remyelinated internode was identified as a thinly-myelinated internode, where a node of Ranvier was bounded by a thickly-myelinated internode on one side and a less-thickly-myelinated internode on the other; as an internode of less than 100 microns in length or below 2 standard deviations from the normal regression line of internodal length against fibre diameter; as an internode joined to one of similar myelin sheath thickness which fulfilled either or both of the previous two criteria. Using the above criteria, remyelinated internodes were found to be shorter than normal; some were very short with no relationship to axon diameter while others were longer, falling within the predicted range for a given fibre diameter. This study illustrates that examination of teased CNS fibres in pathological situations can yield valuable information. However, sampling and technical difficulties are far greater than in comparable studies on peripheral nerve fibres.

Animals↗
PubMed1981

The restoration of conduction by central remyelination.

Conduction has been examined serially through the experimental demyelinating lesion produced by the direct micro-injection of lysophatidyl choline into the cat spinal cord. Conduction was blocked during the phase of demyelination. Remyelination commenced during the latter part of the second week, and conduction through the lesion was restored in some fibres at this time. The refractory period of transmission was initially prolonged. As remyelination proceeded, conduction was restored in increasing numbers of fibres. Within three months the responses were stable and the refractory periods of transmission had returned to normal even though the new internodes were still abnormally thin and were generally shorter than normal. Restoration of conduction by remyelination is likely to contribute to recovery from compressive and traumatic lesions of the central nervous system but probably plays little part in the remissions of multiple sclerosis.

Action Potentials↗