Search PubMed⌕ Search

Biomedical subjects

G Allt

Publications and source records attributed to G Allt.

At least 55 records · Page 3Linked to original sources

Nodes of Ranvier and Schmidt-Lanterman incisures: an in vivo lanthanum tracer study.

The permeability of the tight junctional system of myelin, at the juxtanodal myelin terminal loops and Schmidt-Lanterman incisures, was investigated using the ionic tracer lanthanum (a) in vivo followed by fixation, (b) concurrently with fixation, (c) following fixation. Employing the same methods the juxtanodal membrane complex formed between myelin loops and axolemma was also tested. The results of this study demonstrate that the periaxonal space (between axon and Schwann cell) is apparently accessible to lanthanum via the myelin loop-axolemmal junction, irrespective of the mode of exposure of myelinated fibres to the tracer. Similarly, the tight junctions between adjacent myelin terminal loops apparently do not prevent lanthanum penetration either in living or in fixed nerves. By contrast the tracer obtained access to the extracellular space within incisures only in vivo. The results are interpreted in terms of the permeability of nodes and incisures in vivo to physiologically important ions and related to current concepts of the electrophysiology of the myelinated nerve fibre.

Animals↗

Myelinated nerve fibres and the fate of lanthanum tracer: an in vivo study.

The permeability of the marginal tight junctional system of myelin was tested in the rat employing the electron-dense tracer lanthanum nitrate. Lanthanum was either included in the fixative used for vascular perfusion (at a concentration of 20 mM) or was microinjected in vivo into the sural or tibial nerve (5, 10 and 20 mM). After 5-60 minutes, the microinjected nerves were fixed either by immersion or vascular perfusion. Lanthanum tracer was present in the intraperiod line gap of myelin, irrespective of the mode of application of the tracer, the method of fixation or the time of exposure to lanthanum. However, the tracer was present more extensively when included in the fixative compared with in vivo microinjection. Internodally, lanthanum was usually restricted to the inner, or more commonly, the outer lamellae of larger fibres, while all lamellae were usually penetrated by tracer in smaller fibres. Paranodally, compact myelin was more extensively penetrated. The periaxonal space (between axon and Schwann cell) was readily accessible to tracer. It is concluded that the marginal tight junctional system of myelin is apparently of the 'leaky' type and is permeable to ions. The findings have implications for the electrophysiology and pathophysiology of the myelinated nerve fibre.

Animals↗

The non-directional pattern of axonal changes in Wallerian degeneration: a computer-aided morphometric analysis.

Wallerian degeneration was investigated to determine whether axonal changes occur progressively in a somatofugal or somatopetal direction or simultaneously along the length of the axon. Microtubule density was used as a measure of the extent of axonal degeneration and was assessed by a computer-aided analysis of electron micrographs. The left sural nerves of ten rats were crushed and 30 hours later axonal areas and axonal microtubule numbers were recorded from a large sample of axons at two sites 1 cm and 3 cm distal to the crush. The same recordings were made from the right unoperated nerve at two comparable sites. Statistical analysis of all the data provided no evidence for a somatofugal or reverse direction of degeneration. It is concluded therefore that in Wallerian degeneration axonal changes, as indicated by microtubule dissolution, occur simultaneously along the length of the axon. It is proposed that to interpret the conflicting published data on the direction of fibre degeneration, Schwann cell changes (e.g. myelin ovoid formation) and axonal changes (e.g. microtubule dissolution) should be considered independently since they have different aetiological mechanisms which may account for the differing experimental results reported.

Animals↗

A combined morphological and electrophysiological study of conduction block in peripheral nerve.

The reliability of the electrophysiological criterion of conduction block in determining the presence of focal demyelination in a peripheral nerve has been studied in an animal model. Demyelination was produced in the rat tibial nerve by one or two closely spaced microinjections of lysophosphatidylcholine (LPC). Histological and electrophysiological data were obtained on the acute lesion (up to 6 days), and during recovery (up to 11 weeks). Single LPC injections produced a lesion of very variable severity. Double injections more reliably produced a severe lesion with marked conduction block. Slight axonal damage was occasionally seen in nerves showing severe demyelination. The ratio of amplitude of muscle action potentials evoked by stimuli proximal and distal to the sites of nerve injection was calculated to detect the development of conduction block. The post injection ratio was more than 2 standard deviations below the control mean in 86% of nerves showing signs of demyelination. No control saline injected nerves showed such evidence of conduction block. The severity of the electrophysiological abnormality did not prove a reliable indicator of the severity of the histological lesion, however. The possible reasons for this variability are discussed and it is argued that caution should be exercised when interpreting this particular electrophysiological finding in clinical practice.

Animals↗

Demyelination: a failure of cell communication?

A hypothesis is proposed that demyelination in both the CNS and PNS involves a failure of cell communication between the axon and oligodendrocyte/Schwann cell, as a primary event. The site of communication is assumed to be the paranodal myelin loop-axolemma membrane complex. It is postulated that "cross-talk" between the two cell types can be interrupted, and hence demyelination initiated, by pathophysiological changes in either the axon or myelinating cell. Experimental evidence in support of the hypothesis is cited in so far as it exists.

Axonal Transport↗

The node of Ranvier in early Wallerian degeneration: a freeze-fracture study.

Using the freeze-fracture technique, the sciatic nerve of the rat and rabbit was examined distally at 24 h after crush, with particular reference to the node of Ranvier and paranode. The paranodes, in the majority of myelinated fibres, showed a loss of the cytoplasmic circumferential bands and longitudinal columns and their associated membrane pores which characterise the normal Schwann cell surface. Axonal changes consisting of accumulations of axoplasmic organelles occurred at both the node and paranode. At the nodes large intramembraneous particles in the axolemma (E face) appeared unchanged. Nodal Schwann cell microvilli and paranodal myelin terminal loops were generally unaffected. The findings are discussed in terms of the decrease in amplitude of the action potential which occurs in early Wallerian degeneration.

Action Potentials↗

Effects of capsaicin applied locally to adult peripheral nerve. II. Anatomy and enzyme and peptide chemistry of peripheral nerve and spinal cord.

(1) Capsaicin solution was applied for 15 min around a 1 cm length of sciatic nerve in the mid upper leg of adult rats. (2) Electron microscopic examinations of the nerve in the treated region after 14 days shows no signs of degeneration of either myelinated or unmyelinated fibres attributable to the capsaicin. (3) Fluoride resistant acid phosphatase FRAP disappears from the central terminals of the treated nerve by 7 days. (4) 1.5 mM capsaicin is sufficient to product a complete reduction of FRAP in the spinal cord. (5) The peptides substance P and cholecystokinin (CCK) are markedly depleted in the region of spinal cord terminations of the treated nerve at 14 days. (6) Substance P and CCk are not affected in spinal cord regions other than in the unmyelinated afferent terminal zone. Similarly neurotensin and neurophysin which are not present in afferent fibres are not influenced by capsaicin treatment of the sciatic. (7) It is concluded that there are chemical changes in the spinal cord terminals of fine afferents after local peripheral capsaicin.

Acid Phosphatase↗

Schmidt-Lanterman Incisures. I. A quantitative teased fibre study of remyelinating peripheral nerve fibres.

The quantitative relationship between the number of Schmidt-Lanterman incisures per internode and fibre diameter has been investigated previously in normal, developing, and regenerating fibres and from such data inferences have been made concerning the function of incisures. We have, therefore, examined this quantitative relationship in remyelinating fibres and assessed the implications for incisural function. Using the rat sural nerve, demyelination was induced by local microinjection of lysophosphatidyl choline. At 100 days and 200 days post-injection remyelinating fibres together with normal control fibres were examined quantitatively for the distribution of Schmidt-Lanterman incisures and nodes of Ranvier. Regression lines relating the number of incisures per internode to fibre diameter showed a positive correlation and were not significantly different between the three groups of fibres. The results are compatible with those for normal, developing and regenerating fibres and support the hypothesis of a homeostatic mechanism controlling the number of incisures in relation to fibre diameter and myelin volume. However, in remyelinating fibres, as in regenerating fibres, there is a greater incisural frequency as a consequence of the short internodes.

Animals↗

Schmidt-Lanterman incisures. II. A light and electron microscope study of remyelinating peripheral nerve fibres.

A mechanism has been proposed previously for the formation of Schmidt-Lanterman incisures during ontogeny as myelinated nerve fibres increase in diameter. In this study, the mode of formation of incisures and their development were examined by light and electron microscopy in remyelinating fibres (16-200 d) of the sural nerve of rats following lysophosphatidyl choline (LPC)-induced segmental demyelination. In remyelination, a basic number of incisures is incorporated into the myelin sheath ab initio. Apparently these incisures which are at first circumferentially incomplete, being localised to the region of the mesaxons, progressively extend around the whole circumference of the myelin sheath. As fibre diameter increases, additional incisures are added, seemingly, by the intrusion of Schwann cell cytoplasm between the compact myelin lamellae, from the abaxonal side of the myelin sheath. The progressive differentiation of incisures is described in terms of their complement of organelles. The results are discussed with reference to the possible functions of incisures.

Animals↗

Schwann cell plasma membrane changes induced by nerve crush. A freeze-fracture study.

Twenty-four hours after nerve crush, the Schwann cell plasma membrane and subjacent outer layer of Schwann cell cytoplasm were examined by freeze-fracture in myelinated fibres from the rat and rabbit sciatic nerves. The irregular circumferential bands and longitudinal columns of cytoplasm which characterise the surface of the normal Schwann cell were diminished or had disappeared. Concomitantly, the membrane pores (of micropinocytotic vesicles or caveolae) which are normally present on the bands and columns were also lost. The loss of these specialised features is discussed in terms of the onset of cell dedifferentiation in association with cell division. The Schwann cell plasma membrane acquired a new feature: deep impressions of adjacent collagen fibres, present particularly on the cytoplasmic bands and columns and presumed to be related to a transient increase in fibre diameter.

Animals↗

The role of Schmidt-Lanterman incisures in Wallerian degeneration. II. An electron microscopic study.

The electron microscopy of changes at Schmidt-Lanterman incisures in Wallerian degeneration has been described only briefly previously. We have demonstrated that the changes up to 36 h after nerve crush are chiefly peri-incisural. At 12 h and 24 h 'incisural dilatation' consisted of an intraperiod line separation of peri-incisural myelin lamellae, which began among inner (adaxonal) lamellae extending later to outer (abaxonal) lamellae. The incisure itself showed little or no change. At 36 h, ovoid formation was apparent in most fibres. The sites of fibre cleavage to form ovoids occurred adjacent to incisures at the focal regions of myelin lamellae separation. Even within ovoids the incisures themselves remained intact at 36 h. The fine structural changes at incisures following nerve crush provide an understanding of the increased perceptibility of incisures by light microscopy during early Wallerian degeneration.

Animals↗

The role of Schmidt-Lanterman incisures in Wallerian degeneration. I. A quantitative teased fibre study.

It is conventionally accepted that during the early stages of Wallerian degeneration of myelinated peripheral nerve fibres Schmidt-Lanterman incisures represent the sites at which the myelin sheath, together with enclosed axoplasm, is segmented into myelin ovoids. This mechanism is considered by some authors to be facilitated by the progressive intercalation of additional incisures in order to allow the later division of primary ovoids. We have demonstrated that this reported increase in the number of incisures is a misinterpretation of the changes occurring. By 36 h after crush of the rat sural nerve most myelinated fibres showed segmentation at incisures to form myelin ovoids. At 12 h and 24 h after crush, however, no ovoids were apparent and the number of incisures present was determined from teased fibres by light microscopy using oil immersion. There was no increase in the number of incisures either internodally or paranodally at 12 h and 24 h compared with a normal control population of fibres. However at 12 h, and to a greater extent at 24 h, incisures were more readily apparent than in normal fibres. It is likely, therefore, that previous reports have confused an increase in the number of incisures with an increase in their perceptibility resulting from their progressive dilatation.

Animals↗

Regeneration of the node of Ranvier: a light and electron microscope study.

Regeneration of the node of Ranvier was investigated in the rat peroneal nerve 10-60 days after nerve crush, by light and electron microscopy. At 10 and 20 days after crush nodes of Ranvier were clearly identifiable by electron microscopy but had a relatively simple structure. At 40 days after crush however nodes were highly differentiated showing specialised features such as paranodal bulbs, nodal constriction of the axon, paranodal Schwann cell mitochondria, nodal Schwann cell microvilli, and nodal gap substance. By light microscopy some nodes were identifiable as early as 20 days after crush. At both 30 and 60 days after crush regenerated internodes were uniformly short (means of 275 micronm and 339 micronm respectively).

Animals↗

Crush injury to peripheral nerve. An electron microscope study employing horseradish peroxidase.

Electron microscope observations were made of rat peroneal nerve after crushing using intravenously injected horseradish peroxidase (HRP) as a tracer protein to indicate changes in vascular permeability. At 1/2 h and 2 d after the crush there was gross leakage of HRP from damaged capillaries at the site of injury but none from vessels above or below this. Ultrastructurally vessels at the site of crush showed broken and separated endothelial cells. Proximally and distally there was little abnormal in the vessel walls; vesicles containing HRP were absent and tight-junctions between cells remained intact. Twenty-one days after the crush, leakage of HRP was found both at the site of crush and along the distal segment. The only change in vessel walls was an obvious increase in vesicles filled with HRP. Tracer was also found both in perivascular locations and throughout the endoneurial space.

Animals↗

A study of the perineurium in peripheral nerve pathology.

The response of the perineurium to the following experimental systems was investigated by light and electron microscopy: nerve crush, cold lesion and microinjection of (a) histamine liberator, (b) potassium cyanide, (c) lysophosphatidyl choline (LPC). Where myelin breakdown occurred, lipid globules were seen within Schwann cells, macrophages and also perineurial cells. Where increased vascular permeability occurred, proteinaceous material leaked from endoneurial vessels into the endoneurial space and later appeared between perineurial laminae. It is suggested that the normal homeostatic function of the perineurium is extended in pathology to the removal of protein and lipid debris. In this way the perineurium contributes to the restoration of the normal microenvironment of peripheral nerve fibres.

Animals↗