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Biomedical subjects

G M Bray

Publications and source records attributed to G M Bray.

At least 55 records · Page 3Linked to original sources
PubMed1981

Ongoing block of Schwann cell differentiation and deployment in dystrophic mouse spinal roots.

In the spinal roots of dystrophic mice, there are bundles of unensheathed axons and two populations of axon-associated cells: the typical Schwann cells of myelinated fibers and 'uncommitted' cells at the margin of the bundles. Because these 'uncommitted' cells continue to divide in adult animals but fail to ensheath the axons they appose, they can be labelled with tritiated thymidine. In the present experiments, we show that these cells may differentiate into typical Schwann cells of myelinated or unmyelinated fibers when spinal roots from [3H]thymidine-labelled dystrophic mice are grafted into the sciatic nerves of non-dystrophic animals. Thus, this study demonstrates that the 'uncommitted' cells of dystrophic spinal roots are undifferentiated Schwann cells whose differentiation in the intact spinal roots is continuously prevented by some unknown mechanism.

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PubMed1981

Influences of the glial environment on the elongation of axons after injury: transplantation studies in adult rodents.

Tissue transplantation methods, previously used to study neural development, myelination and inherited disorders of myelin can be applied also to the investigation of repair and regeneration in the mammalian CNS. The elongation of axons from injured peripheral nerve of CNS has been studied in adult mice and rats by observing the growth of axons into PNS or CNS tissue grafts. Following spinal cord injury and also after transplantation of optic nerves into the PNS there is axonal sprouting but these neuronal processes fail to elongate more than a few mm into the surrounding glia. On the other hand if segments of a peripheral nerve are grafted into the transected spinal cord, axons arising from spinal neurons and dorsal root ganglia become associated with the transplanted Schwann cells and elongate along the graft, approximately 1 cm. Recently the elongation of axons from spinal and medullary neurones was studied using a new experimental model which employed PNS grafts as 'bridges' to connect the spinal cord and the brain stem. In a series of adult C57BL/6J mice and Sprague Dawley rats, autologous segments of sciatic nerve were used to create 'bridges' between the lower cervical or upper thoracic spinal cord and the medulla oblongata. The spinal cord between these two levels was left intact. Grafted segments examined by light and electron microscope 1-7 months after surgery were well innervated by Schwann cell ensheathed axons that had grown the entire length of the graft (2 cm in mice and 3.5 cm in rats). The origin and termination of these axons were determined by transecting the regenerated grafts and applying horseradish peroxidase to the cut ends. Retrogradely labelled neurones were found to be distributed widely in the gray matter of the spinal cord and medulla near the sites of insertion of the graft. Anterogradely labelled fibres coursing within the graft penetrated the CNS for short distances, approximately 2 mm. These new results indicate that following CNS injury a conducive glial environment does allow spinal and brain stem neurones to elongate axons for distances that can be greater than those they usually extend for in the intact animal. This evidence that the regenerative response of similar axons differs in CNS and PNS neuroglia supports the hypothesis that influences arising from the environment play an important role in the success or failure of regeneration. The regenerative potentiality of central neurones may be expressed only when the CNS neuroglial environment is changed to resemble that in the PNS.

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PubMed1979

Node-like areas of intramembraneous particles in the unensheathed axons of dystrophic mice.

The unensheathed axons in the spinal roots of adult dystrophic mice were examined by freeze-fracture electron microscopy. In most areas of these abnormal fibers the distribution of intramembraneous particles was similar to that of the internodal segments of normal axons with many more particles on the PF (internal) leaflets of these axonal surface membranes than on their EF (external) leaflets. However, patches of axonal membranes were also observed in which the distribution of intramembraneous particles resembled that seen in nodes of Ranvier.

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PubMed1978

Conduction of nervous impulses in spinal roots and peripheral nerves of dystrophic mice.

Conduction was studied in the sacral ventral roots and ventral tail nerves of dystrophic mice (dy/dy) and phenotypically normal littermates. In myelinated ventral root fibers of normal mice, conduction velocity was uniform with internodal conduction time 45 +/- 5 musec (26 degrees C). In ventral root fibers of dystrophic mice, conduction velocity was decreased and strikingly non-uniform; both saltatory and continuous conduction were observed in different portions of the same nerve fiber. Continuous conduction with velocity less than 2 m/sec (26 degrees C) was characteristically observed in mid-root where the axons are bare; conduction was saltatory close to the exit from the spinal canal and near the spinal cord where the axons are myelinated. Maximum conduction velocity in ventral tail nerves was 21 +/- 3 m/sec for dystrophic mice and 31 +/- 4 m/sec for littermate controls (37 degrees C). Internodal lengths were somewhat decreased in the dystrophic peripheral nerves but there was no significant difference in maximum fiber diameters, myelin thickness or nodal morphology between dystrophic and normal nerves.

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PubMed1977

Ouabain binding sites in skeletal muscle from normal and dystrophic mice.

The specific binding of tritiated ouabain was used to estimate the density of Na+-K+-ATPase sites ("Na+-pump" sites) in segments of skeletal muscle from normal and dystrophic mice. Ouabain binding was approximately 4 times greater in red (soleus) muscle than in white (superficial gastrocnemius) muscle from normal animals. In dystrophic soleus muscles, ouabain binding was decreased by nearly one-half. Because Na+-K+-ATPase activity is associated with plasma membranes, these observations constitute further evidence for a sarcolemmal abnormality in dystrophic mice.

Adenosine Triphosphatases↗
PubMed1976

Multipotentiality of Schwann cells in cross-anastomosed and grafted myelinated and unmyelinated nerves: quantitative microscopy and radioautography.

Cross-anastomoses and autogenous grafts of unmyelinated and myelinated nerves were examined by electron microscopy and radioautography to determine if Schwann cells are multipotential with regard to their capacity to produce myelin or to assume the configuration seen in unmyelinated fibres. Two groups of adult white mice were studied. (A) In one group, the myelinated phrenic nerve and the unmyelinated cervical sympathetic trunk (CST) were cross-anastomosed in the neck. From 2 to 6 months after anastomosis, previously unmyelinated distal stumps contained many myelinated fibres while phrenic nerves joined to proximal CSTs became largely unmyelinated. Radioautography of distal stumps indicated that proliferation of Schwann cells occurred mainly in the first few days after anastomosis but was also present to a similar extent in isolated stumps. (B) In other mice, CSTs were grafted to the myelinated sural nerves in the leg. One month later, the unmyelinated CSTs became myelinated and there was no radioautographic indication of Schwann cell migration from the sural nerve stump to the CST grafts. Thus, Schwann cell proliferation in distal stumps is an early local response independent of axonal influence. At later stages, axons from the proximal stumps cause indigenous Schwann cells in distal stumps from the previously unmyelinated nerves to produce myelin while Schwann cells from the previously unmyelinated nerves to produce myelin while Schwann cells from the previously myelinated nerves become associated with unmyelinated fibres. Consequently, the regenerated distal nerve resembled the proximal stump. It is suggested that this change is possible because Schwann cells which divide after nerve injury reacquire the developmental multipotentiality which permits them to respond to aoxonal influences.

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PubMed1976

Schwann cell multiplication after crush injury of unmyelinated fibers.

The intensity and duration of Schwann cell multiplication in unmyelinated fibers after crush injury of cervical sympathetic trunks (CSTs) in adult mice was studied using radioautography and electron microscopy. At the level of crush, labeling indexes rose to 22.5% on the second day after injury, but distal to this level, labeling reached a peak of only 2.5%. By the ninth day labeling declined to 1% or less at both sites. Electron microscopy confirmed that the increase in nuclei at the crush was mainly an increase in Schwann cells. Thus, the intensity of Schwann cell multiplication differed between crush and distal sites along the same unmyelinated nerve. The Schwann cell proliferation in the distal CSTs was less intense than that reported in previous studies on myelinated nerves.

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PubMed1976

Potential of Schwann cells from unmyelinated nerves to produce myelin: a quantitative ultrastructural and radiographic study.

In adult mice, most fibres in the cervical sympathetic trunk (CST) are unmyelinated whereas a large proportion of sural nerve fibres are myelinated. This study of nerve grafts in syngeneic mice was designed to determine if Schwann cells originating from the unmyelinated CST would produce myelin when in contact with regenerating axons of the sural nerve. Quantitative microscopy of triated thymidine-labelled CST segments grafted to unlabelled sural nerve stumps revealed that, one month after grafting, previously unmyelinated grafts contained many myelinated fibres. By phase and electron microscope radioautography, nearly 40% of the myelin-producing cells in the reinnervated graft were shown to have originated in the unmyelinated CST. These findings indicate that Schwann cells originating from unmyelinated fibres are able to differentiate into myelin producing cells.

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PubMed1976

Neonatal neuronal loss in rat superior cervical ganglia: retrograde effects on developing preganglionic axons and Schwann cells.

Beginning prenatally and during the first week after birth, there is normally a loss of axons in rat cervical sympathetic trunk. To test the hypothesis that this spontaneous axonal loss represents a natural process whereby an excessive number of immature preganglionic axons in the cervical sympathetic trunk adapts to the neuronal population in the superior cervical ganglion, the number of nerve cells in the superior cervical ganglion was reduced in newborn rats by administration of nerve growth factor antiserum, 6-hydroxy-dopamine or postganglionic anxotomy. Quantitative ultrastructural studies of these animals at later stages of development revealed that, with each method, the number of preganglionic axons and Schwann cells was reduced to nearly one-third of normal. These findings indicate that the superior cervical ganglion plays an important role in the development of the cervical sympathetic trunk. Removal of ganglionic cells causes a retrograde loss of preganglionic fibres. This process probably represents an exaggeration of the normal mechanism for elimination of redundant axons. Because the changes in axonal numbers are associated with similar reductions in the number of Schwann cells, it can also be concluded that postnatal Schwann cell proliferation is influenced by axonal populations.

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PubMed1976

Three dimensional analysis of unmyelinated fibers in normal and pathologic autonomic nerves.

The technique of serial-section electron microscopy and diagrammatic three dimensional reconstructions has been used to assess normal and pathological unmyelinated nerve fibers from a peripheral autonomic nerve: the rat cervical sympathetic trunk. Within this predominantly unmyelinated nerve, there is a complex arrangement of axons into longitudinally oriented bundles brought together by chains of Schwann cells. Each bundle is subdivided into smaller components by the cytoplasmic processes of Schwann cells; such subdivisions, which are basal lamina-enclosed masses of Schwann cell cytoplasm, when viewed on cross-sectional electron micrographs, are termed Schwann cell units. The size and shape of each Schwann cell unit varies along the length of fibres, but the diameter of individual axons shows little variation over the segments studied. Axonal branching was not observed in normal unmyelinated nerves. Crush injury and x-irradiation produces different patterns of alteration in the axon-Schwann cell relationships of unmyelinated nerves. Following crush injury, Schwann cell processes increase in diameter and contain numerous small diameter axonal sprouts. Many of the regenerating axons remain thin while others reacquire a normal diameter. X-irradiation affects Schwann cells leading to retraction of their processes and the appearance of naked axonal segments.

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