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Biomedical subjects

S K Ludwin

Publications and source records attributed to S K Ludwin.

At least 55 records · Page 3Linked to original sources
PubMed1984

An immunohistochemical study of myelin proteins during remyelination in the central nervous system.

The process of remyelination in the superior cerebellar peduncles of mice following demyelination with Cuprizone was studied immunohistochemically using antisera to myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). Demyelination occurred after formation of myelinic vacuoles and resulted in almost complete loss of demonstrable MBP and MAG from the peduncle. Prior to the onset of remyelination, oligodendrocytes with cytoplasmic staining for both proteins appeared in the peduncle. These cells were then associated with remyelinating axons. The axons were remyelinated in clusters until the MBP and the MAG in the whole peduncle were reconstituted, although the axon sheaths were thinner than those in normal animals. The results show that the immunohistochemical distribution of MBP and MAG in remyelinating axons resembles that in normal axons, and that the expression of myelin proteins in oligodendrocytes during remyelination reverts to that seen during normal development.

Animals↗
PubMed1984

Long-term remyelination fails to reconstitute normal thickness of central myelin sheaths.

The relationship between the thickness of the myelin sheath and the square area of the axon was measured in both short-term and long-term remyelinated axons following demyelination in the central nervous system, and compared with that of controls. The normal linear relationship between thickness of myelin sheath and axon size was not present in either group of remyelinated axons even though there was a trend, not statistically significant, in the long-term remyelinated animals to approach that of normal animals.

Analysis of Variance↗
PubMed1984

Rhabdoneuroglial heterotopias of the pontine leptomeninges in trisomy 13.

An unusual heterotopia of striated skeletal muscle and glial tissue occurred in the pontine meninges of a stillborn male showing feature of trisomy 13 and an Arnold-Chiari malformation. In two other reports of this type of heterotopia, the location and association with trisomy 13 has been the same. An error in tissue differentiation at the pontine flexure is suggested to account for this relationship.

Adult↗
PubMed1982

Neuroaxonal dystrophy in young adults: a clinicopathological study of two unrelated cases.

The clinical and pathological features of two unrelated sporadic cases of neuroaxonal dystrophy occurring in young adults are described. Initial clinical manifestations in both patients were those of primary psychiatric disorders. They subsequently developed extrapyramidal symptoms, dementia, cerebellar ataxia, and corticospinal dysfunction, but neither demonstrated myoclonic seizures. In one patient the diagnosis was made before death by brain biopsy. On pathological examination both patients showed a generalized distribution of spheroids within the central nervous system and, in one, in the peripheral nerves. In both patients, Lewy bodies were demonstrated in the pigmented brainstem nuclei. In addition, one patient showed ultrastructurally verified Lewy bodies in the cerebral cortex. Although these two cases could be considered examples of juvenile neuroaxonal dystrophy, we prefer to regard them as transitional forms in a disease spectrum with classic infantile neuroaxonal dystrophy and Hallervorden-Spatz disease at the two extremes.

Adult↗
PubMed1981

Evidence for a "dying-back" gliopathy in demyelinating disease.

Recurrent demyelination was produced in mice by Cuprizone administration. During the second course of Cuprizone, the animals showed greater resistance to the toxin and demyelination occurred slowly and was complete only after prolonged periods. The earliest changes in oligodendrocytes occurred in the most distal processes, the inner cytoplasmic tongues, which showed degenerative changes 3 to 4 weeks before degeneration of the oligodendrocyte cell bodies or demyelination occurred. The results show for the first time that in demyelinating disease, a "dying-back" process similar to that described in axonal disease can affect the oligodendrocyte.

Animals↗
PubMed1981

The demonstration of recurrent demyelination and remyelination of axons in the central nervous system.

A model for studying recurrent demyelination and remyelination in the central nervous system was developed by means of repeated administration of Cuprizone to mice. In contrast to the demyelination seen during the first course of Cuprizone, the recurrent demyelination was markedly protracted, displayed features of a "dying-back" gliopathy, and resulted in a greatly reduced inflammatory and glial reaction. The repeat remyelination also occurred at a slower tempo, varied markedly in completeness, and was associated with a diminished regeneration of oligodendrocytes. These results demonstrated that axons of the central nervous system in this model can be recurrently remyelinated if oligodendrocytes are available, that regeneration of oligodendrocytes is dependent upon the tissue reaction to demyelination, and that remyelinated axons are not more susceptible to demyelination than normal ones.

Animals↗
PubMed1980

Chronic demyelination inhibits remyelination in the central nervous system. An analysis of contributing factors.

The remyelinative capacity of the central nervous system was investigated in the superior cerebellar peduncles of mice chronically demyelinated for 6 to 7 months by the administration of Cuprizone. It was found that, although the axons retained their capacity for remyelination, this capacity was greatly reduced compared to acutely demyelinated animals. The possible causes for this reduction were examined, and it was concluded that the limiting factor was the decreased availability of oligodendrocytes for remyelination, rather than inherent factors in the axons, or changes in the surrounding glial environment. The implications for both experimental and clinical disease are discussed.

Aging↗
PubMed1979

The perineuronal satellite oligodendrocyte. A role in remyelination.

Demyelination was induced in the superior cerebellar peduncles of weanling mice by the administration of Cuprizone. Remyelination occurred when the animals were replaced on a normal diet. Perineuronal satellite oligodendrocytes in the periventricular gray were clearly seen to be remyelinating axons. This study demonstrates for the first time the role of these cells in remyelination, and raises the possibility that they may be involved in normal myelination of the central nervous system.

Animals↗
PubMed1979

An autoradiographic study of cellular proliferation in remyelination of the central nervous system.

The proliferation and origin remyelinating oligodendrocytes was studied by light and electron miscrosopic autoradiography in the superior cerebellar peduncles of mice demyelinated by Cuprizone. In the early phases of demyelination, the cells undergoing mitotic activity were macrophages and astrocytes. In the later phases of demyelination, immature proliferating oligodendrocytes appeared; these differentiated into mature (dark) oligodendrocytes which were responsible for the remyelination of axons seen when animals were again placed on normal diets. The pattern of differentiation recapitulated that seen in developing oligodendrocytes in normal animals. Dark oligodendrocytes did not show mitotic activity. There was no mitotic activity in the subependymal cells around the fourth ventricle adjacent to the superior cerebellar peduncles. This study demonstrates the regenerative capacity of oligodendrocytes and their ability to carry out remeylination in the central nervous system.

Animals↗
PubMed1978

Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity.

Male weanling mice (Biobreeding Laboratories) exposed to the drug Cuprizone (biscyclohexanone, oxaldihydrazone) in the diet for periods of 6 weeks and longer, consistently showed almost complete demyelination of the superior cerebellar peduncle. The demyelination was primary and followed degeneration of oligodendrocytes and their processes, whereas axons remained intact. After formation of myelinic vacuoles and removal of myelin by macrophages and astrocytes, the axons became invested with astroglial processes. As part of the glial response to demyelination, numerous reactive or immature cells appeared, some of which were identified as being either astrocytic or oligodendrocytic in nature. Some mature oligodendrocytes survived. When allowed to recover on a normal diet, remyelination began within a week, and progressed until all axons were myelinated. The mechanism of remyelination appeared similar to the spiral wrapping mechanism seen in normal development. The myelinating cell in all cases was the mature oligodendrocyte. Sources for these oligodendrocytes include residual surviving oligodendrocytes, differentiation of immature forms, and possibly the perineuronal satellite cell. The sheaths eventually reached a thickness approximately half that of normal development, with a disturbed relationship between myelin thickness and axon diameter. A visual impression of shortened internodal length was obtained. It is concluded that the Cuprizone model is an excellent situation in which to study the cellular mechanisms of demyelination and remyelination.

Animals↗
PubMed1976

The topographical distribution of S-100 and GFA proteins in the adult rat brain: an immunohistochemical study using horseradish peroxidase-labelled antibodies.

The cytological and topographical distribution of S-100 and glial fibrillary acidic (GFA) proteins in the adult rat brain has been compared using the horseradish peroxidase-labelled antibody technique. Both proteins are present in astrocytes and structures composed of astrocytic processes, namely the glial limitans and the perivascular membranes, but the cytological localization varies between the two proteins. S-100 is found in the nucleus and cytoplasm whereas GFA protein is confined to the cytoplasm. Neither is found in neurons, but S-100 is present in some oligodendroglia, suggesting a general regulatory role in glia. Although GFA protein in present in both protoplasmic and fibrous astrocytes, it is more prominent in the latter, confirming its association with astrocytic filaments.

Animals↗
PubMed1976

In vitro astrocytic differentiation from embryoid bodies of an experimental mouse testicular teratoma.

Astrocytic differentiation in monolayer cultures of ascitic embryoid bodies from the experimental teratoma OTT-6050 was studied by conventional light microscopy and by indirect immunofluorescence with antisera to glial fibrillary acidic (GFA) protein, a protein specific for astorcytes. Primitive neuroepithelial cells were identified in 24-hour cultures. Within 72 hours, two cell types diverged. One cell type, with a flattened epithelial morphology in early cultures, demonstrated delicate GFA protein-positive fibrils within 48 hours. In later cultures, this type progressively displayed more typical stellate astrocytic features, with denser, more compact GFA protein-positive fluorescence in the perinuclear cytoplasm and cell processes. As indicated by GFA protein expression, the appearance of astrocytes of typical morphology therefore was preceded by biochemical differentiation. The second cell type, interpreted as neuroblastic, failed to demonstrate GFA protein and had a small perikaryon with slender bipolar processes that were argyrophilic with Bodian's protargol in late cultures. Divergent neuroepithelial differentiation occurred within mitotically active cell populations and proceeded without apparent tissue relationships to other germ layer derivatives.

Animals↗
PubMed1975

Papillary meningioma: a malignant variant of meningioma.

A series of 17 meningiomas histologically characterized by a papillary pattern is reported. This pattern was invariably associated with other histologic features of malignancy. The tumors often displayed aggressive clinical behavior marked by a high rate of local recurrence or the development of distant metastases. A relatively large proportion occurred in children. It is suggested that this variant of meningioma is sufficiently characteristic to justify its separation as a distinct clinicopathologic entity.

Adult↗
PubMed1975

Malignant meningioma metastasizing through the cerebrospinal pathways.

A 53-year old man presented with a malignant meningioma which was incompletely removed. The tumour subsequently metastasized through the cerebrospinal pathways causing clinical signs through invasion of the cranial nerve roots. Microscopically, the metastatic deposits displayed a papillary pattern and increased anaplastic cytological features.

Brain Neoplasms↗
PubMed1975

Oxygen toxicity in the newborn. The effect of prolonged 100 per cent O2 exposure on the lungs of newborn mice.

A comprhensive morphologic study of pulmonary oxygen toxicity was undertaken on 78 newborn mice of a single, highly inbred strain continuously exposed to 100 per cent oxygen at normal atmospheric pressure for 7 days. The survival rate was 95 per cent through the first 4 days and 75 per cent through the 7th day. Our findings indicate that response to continuous exposure to 100 per cent oxygen can be divided arbitrarily during the first 7 days into three different phases. During the first, or acute toxic, phase (which generally extends into the 3rd day of exposure), mechanisms, probably adaptive in nature, are sufficiently developed in some of the newborn animals to permit them to survive a continuous 7-day exposure. The acute toxic phase is followed by the critical, high mortality phase, which lasts 3 to 4 days. During this phase, which can be subdivided into a continuum of several stages, the changes seen in the initial, acute toxic phase may progress to more pronouced injury. If the injury is severe, massive pulmonary edema and hemorrhage occur, accounting probably for the deaths of most of the animals in previous similar experimental studies and of 25 per cent of our animals by the 7th day. The second stage of this high mortality phase, being more clearly reactive, consists of a progression of reactive mitochondrial changes, proliferation of granular pneumocytes, and a return to normal of the features of the membranous pneumocytes. The beginning of the third phase, the chronic injury and repair phase, is characterized by the appearance of fibroblasts and a concomitant moderate increase in the amount of collagen.

Animals↗
PubMed1975

An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. I. Light microscopic and tissue and organ culture observations.

The various stages of divergent neuroepithelial differentiation were studied in the solid transplants of a transplantable mouse testicular teratoma (OTT-6050) maintained in both ascitic and solid forms. They included: a) areas of undifferentiated medullary epithelium corresponding to the rare human medulloepithelioma; b) areas of neuroblastic differentiation corresponding to neuroblastoma, with more mature neuronal differentiation corresponding to ganglioneuroma or, when mixed with glial elements, to ganglioglioma; and c) more mature neuroglial areas resembling astrocytoma, oligodendroglioma or ependymoma, as well as more primitive areas corresponding to ependymoblastoma. In tissue culture using collagen-coated coverslips, astrocytic differentiation was found in the outgrowth zone after 15 days, confirmed by immunofluorescence with antibodies to an astroglia-specific protein. In organ culture systems, glial components, including ependymal structures, were preserved in tumor explants, and astrocytic differentiation, as expressed by glial fiber formation, was increased after 4 to 6 weeks in vitro. No neuronal differentiation was demonstrable, however. The neuroepithelial component of this experimental teratoma may provide a model for the study of neoplastic neuroepithelial differentiation.

Animals↗