Influence of fatty acid content of lysophosphatidyl choline on its myelinotoxic properties.

The efficacy of lysophosphatidyl choline (LPC) type I and type IV in producing demyelination was assessed in rat tibial and sural nerve. By light and electron microscopy, a greater myelinolytic activity was demonstrated with type I, and concomitantly electrophysiology showed a more severe conduction block. In teased nerve preparations and 1-microns thin sections, demyelinated fibres were more frequent with LPC type I. At 1 h after injection, electron microscopy showed much more extensive myelin lysis in the form of fine vesicular debris. By 6 days, completely demyelinated fibres were much more common and associated Schwann cells contained either small quantities or no myelin debris. With type IV LPC, cytopathological changes were more extensive at 1 h. A minority of Schwann cells showed swollen hydropic cytoplasm and degradation of organelles. Axonal retraction from the myelin sheath occurred in occasional fibres, and in a few unmyelinated fibres axoplasm showed organelle depletion and increased granularity. By 6 days, Schwann cells still contained large quantities of gross myelin debris and had often retracted to expose extensive areas of axolemma. The findings suggest that the two types of LPC have different myelinolytic actions, which may be related to their different fatty acid content. A possible role for the two types of LPC in 'bystander demyelination' is considered.     

A quantitative ultrastructural study of dorsal root regeneration

Regeneration in rat lumbo-sacral dorsal roots was studied 5–71 days following crush lesions. Wallerian degeneration occurred up to 20 days. At 11 days degenerating myelin was found in both Schwann cells and macrophages.Myelination was first observed 4 mm central to the crush at 7 days, and myelin became compact when the mesaxon exhibited 3.5 turns about the axon (about 11 days post-operatively). At 71 days, 69% of all fibres were myelinated, compared with 36% in normal roots. An example of 2 axons myelinating within the same Schwann cell occurred at 20 days.In normal roots curvilinear relationships were found between axon diameter and fibre diameter, myelin thickness and axon diameter, and between g and fibre diameter. In contrast, linear relationships between these parameters occurred in post-operative roots up to 71 days. Curvilinearity returned at 71 days. Alterations in the relationship between axon diameter and myelin thickness during regeneration indicated that myelin growth lagged behind axon growth throughout, but was more noticeable in larger calibre fibres. By 71 days, larger fibres exhibited disproportionately thin myelin, whilst small fibres possessed abnormally thick myelin compared to normal fibres of similar calibre.Regeneration was limited by axons failing to make successful central synaptic connections and by the poor metabolic response of dorsal root ganglion cells to sectioning of their central processes.     

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.     

BUCKTHORN NEUROPATHY: EFFECTS OF INTRANEURAL INJECTION OF KARWINSKIA HUMBOLDTIANA TOXIN

Ingestion of the endocarp of the coyotillo fruit, Karwinskia humboldtiana , a shrub of the buckthorn family, causes 'Buckthorn neuropathy' in man and animals. Two neurotoxic compounds T496 and T544 were isolated from the endocarp and each toxin was dissolved in sesame oil and injected into the sciatic nerve of rats. The nerves were subsequently examined by teasing and as sections by light and electron microscopy. During the first 3–4 days after injection, oil droplets, probably containing toxin, were observed in the cytoplasm of Schwann cells with intact myelin sheaths. Clinical signs of weakness in the limb first appeared at 5–6 days and were accompanied by segmental demyelination mainly of the larger fibres. These observations suggest that the toxins have a primary action on Schwann cell metabolism. The results of local injection of purified toxins are discussed in relation to reports of nerve damage in animals following oral administration of the endocarp where intramyelin vacuole formation and segmental demyelination are prominent features.     

Demyelination and early remyelination in experimental allergic encephalomyelitis passively transferred with myelin basic protein-sensitized lymphocytes in the Lewis rat

Histological studies were performed on Lewis rats with experimental allergic encephalomyelitis (EAE) passively transferred by myelin basic protein (MBP)-sensitized syngeneic spleen cells in order to determine the relationship between demyelination and neurological signs. Neither inflammation nor demyelination was present on the day prior to the onset of neurological signs but both were present in the spinal roots and spinal cord on the day of onset of tail weakness (4 days after passive transfer). Demyelination and the neurological signs both increased over the next 48 h. There was evidence that the caudal roots were more severely affected than the rostral roots. The peripheral nerves were spared. Demyelination in the spinal cord was concentrated in the dorsal root entry and ventral root exit zones. The initial stages of repair of demyelinated spinal root fibres by Schwann cells were observed on the earliest day that clinical recovery commenced (day 7). At this time some demyelinated fibres were closely associated with debris-free Schwann cells, and occasional fibres were completely invested by 1-2 layers of Schwann cell cytoplasm. Remyelination (compact myelin lamellae formation) by Schwann cells was first observed in the spinal roots on day 9. By the time of complete clinical recovery (day 11) the majority of affected spinal root cores had thin new myelin sheaths. Repair of central nervous system myelin by oligodendrocytes was slower than peripheral nervous system myelin repair. Investment of demyelinated spinal cord axons by oligodendrocytes was observed on day 9, and remyelination by these cells was seen on day 10. We conclude that the neurological signs of passively induced MBP-EAE can be accounted for by demyelination of the lumbar, sacral and coccygeal spinal roots and spinal cord root entry and exit zones, and that the subsequent clinical recovery can be explained by investment and remyelination of demyelinated peripheral and central nervous system fibres by Schwann cells and oligodendrocytes respectively.     

Radiation-induced Reductions in Macrophage Recruitment Have Only Slight Effects on Myelin Degeneration in Sectioned Peripheral Nerves of Mice

Macrophage recruitment into the distal nerve stump of the cut or crushed sciatic or saphenous nerves of C57BL/6J mice was reduced by prior whole body irradiation. This procedure was successful in keeping the numbers of cells stained with the mouse macrophage-specific antibody F4/80 to the levels found in unsectioned nerves. Quantitative image analysis of immunostained sections showed that the rate of loss of myelin basic protein was identical in nerves from irradiated and unirradiated mice up to 5 days but thereafter was slower in macrophage-deprived nerves. Similar analysis of semithin sections stained with toluidine blue detected more undegenerated myelin in the nerves from irradiated mice 10 days after operation. Quantitative counts made from electron micrographs of the sectioned nerves at 7 days also showed slightly less extensive myelin breakdown in the nerves from irradiated mice. Complete removal of myelin from some Schwann cells can occur without macrophages, but macrophages accelerate the removal of myelin in the later stages of Wallerian degeneration. It is concluded that there are two phases to the breakdown of myelin in peripheral nerves undergoing Wallerian degeneration: an initial stage entirely dependent on the activity of Schwann cells and a later stage dependent on both Schwann cells and the presence of macrophages.     

Remyelination by cells introduced into a stable demyelinating lesion in the central nervous system

Schwann cells from an autogeneic peripheral nerve source were injected into an established demyelinating lesion produced by the direct micro-injection of diphtheria toxin into the cat spinal cord. In control diphtheria toxin lesions, which were not injected with Schwann cells, demyelination and some oligodendrocyte remyelination was seen but Schwann cell remyelination was not observed. In diphtheria toxin lesions which were wholly confined to the posterior columns, Schwann cell myelin was not seen before 3 weeks after cell injection. The Schwann cell myelinated fibres occurred singly or in small groups within the posterior columns and were considered to have been myelinated by injected Schwann cells. By one month Schwann cell myelinated fibres had thick myelin sheaths but many demyelinated axons remained. By contrast, in more extensive diphtheria toxin lesions there was widespread Schwann cell remyelination of central axons at all stages examined after cell injection. The Schwann cell myelinated fibres were grouped in large numbers around the damaged dorsal root entry zones, the likely source of Schwann cells in these lesions. It is concluded that CNS remyelination may be improved by the injection of peripheral Schwann cells although the extent of remyelination is limited. One facet limiting remyelination may be the concentration of Schwann cells that it is possible to inject with present techniques. Functional recovery remains to be investigated.     

Morphological changes in IgM paraproteinaemic neuropathy

Summary Sural nerve biopsies were examined from two patients with neuropathy associated with IgM kappa [anti-myelin-associated glycoprotein (MAG)] paraproteinaemia. Both nerves had a moderate loss of myelinated fibres. The pathology in one was of a chronic primary demyelinating type, in the other it was associated with axonal atrophy. Widened myelin (WM) was seen in both nerves affecting over 80% and 50% of myelinated fibres, respectively. The WM was associated with deposition of material which sometimes appeared granular but could also display a highly organised pattern, an appearance not previously described in these neuropathies. Granular material was also identified at the external surface of the Schwann cells of myelinated, but not of unmyelinated, fibres. WM was seen not only at the outer lamellae (a commonly observed site) but also at terminal myelin loops at the paranode, at Schmidt Lanterman incisures and at the inner and outer mesaxon. Material was also seen on the inner (adaxonal) Schwann cell suface. These are all sites associated with the presence of MAG. Other pathological features are described, including evidence of impairment of remyelination, abnormal Schwann cell/axon specialisations and the presence of tomaculous bodies. The implications of these findings are discussed.     

Local administration of vasoactive intestinal peptide after nerve transection accelerates early myelination and growth of regenerating axons

Our goal was to determine whether local injections of vasoactive intestinal peptide (VIP) promote early stages of regeneration after nerve transection. Sciatic nerves were transected bilaterally in 2 groups of 10 adult mice. In the first group, 15 microg (20 microL) of VIP were injected twice daily into the gap between transected ends of the right sciatic nerve for 7 days (4 mice) or 14 days (6 mice). The same number of mice in the second group received placebo injections (20 microL of 0.9% sterile saline) in the same site, twice daily, for the same periods. After 7 days, axon sizes, relationships with Schwann cells and degree of myelination were compared in electron micrographs of transversely sectioned distal ends of proximal stumps. Fourteen days after transection, light and electron microscopy were used to compare and measure axons and myelin sheaths in the transection gap, 2-mm distal to the ends of proximal stumps. Distal ends of VIP-treated proximal stumps contained larger axons 7 days after transection. More axons were in 1:1 relationships with Schwann cells and some of them were surrounded by thin myelin sheaths. In placebo-treated proximal stumps, axons were smaller, few were in 1:1 relationships with Schwann cells and no myelin sheaths were observed. In VIP-treated transection gaps, measurements 14 days after transection showed that larger axons were more numerous and their myelin sheaths were thicker. Our results suggest that in this nerve transection model, local administration of VIP promotes and accelerates early myelination and growth of regenerating axons.     

Fine structural changes in the sural nerve of patients with acanthocytosis

Summary The fine structure of sural nerve biopsies is described in two brothers with normo-lipoproteinaemic acanthocytosis and an associated neurological syndrome. There was a severe reduction of myelinated fibres. The Schwann cells had an increased population of lysosomes and contained remnants of myelin. The myelin lamellae were often split at the intraperiod lines. Centrioles were found in Schwann cells, fibroblasts and endothelial cells. The significance of these findings is discussed.     

Degeneration of non-myelinated axons in the rat sciatic nerve following lysolecithin injection

Summary Lysolecthin has been used in many studies to induce demyelination in peripheral nerves. In the present investigation lysolecithin (lysophosphatidyl choline) was injected into rat sciatic nerves at a dose of 2–3 m of a 10 mg/ml solution in order to study the effects of this lipid on cellular elements other than myelin within the nerve. Twenty-four hours after injection, there was splitting of myelin, lysis of Schwann cells, and complete loss of non-myelinated axons and their Schwann cells at the site of injection. Numerous swollen non-myelinated axons containing accumulated organelles were seen just proximal to the site of injection at 48 h. Loss of non-myelinated axons from the distal part of the nerve was also noted at 3 days after injection but by 7 days regenerating non-myelinated axons had re-appeared in the distal part of the nerve. Although demyelination, followed by remyelination was a prominent feature in the injected segment of the nerve, no damage to myelinated axons was detected. These results suggest that the presence of the myelin sheath protects the large myelinated axons against the action of lysolecithin, but with lysis of Schwann cells, the non-myelinated axons are exposed to the action of lysolecithin. Apart from selective damage to non-myelinated fibres with subsequent degeneration, it is also possible that lysolecithin interferes with axoplasmic flow in non-myelinated axons.     

Development of the amyelinated lesion in the ventral root of the dystrophic mouse. Ultrastructural, quantitative and autoradiographic study

Postnatal development of the L5 ventral spinal root was studied in dystrophic (Bar Harbor 129 ReJ dy/dy) and normal mice by ultrastructural, quantitative and autoradiographic methods. Ultrastructural studies of normal roots showed that at birth most axons were invested with Schwann cell cytoplasm, while in dystrophic roots there were large groups of amyelinated fibres. By the 4th day, the normal animal had no naked axons, while large groups of amyelinated fibres remained in the dystrophic animals. Further abnormalities present in the ventral roots of dystrophic mice, both at birth and on the 4th day, included the presence of Schwann cells not committed to any axons, and deficiency of the Schwann cell basement membrane.Quantitative studies showed that at birth the number of myelinated fibres in dystrophic roots was 34% of normal, and remained constant throughout life, while in normals there was a 10-fold increase within 15 days. The number of dystrophic Schwann cell nuclei per whole L5 root transverse section, when corrected for nuclear and root length, was 76% of normal at birth, 20% 15 days later and 50% in adults. The rate of proliferation of dystrophic Schwann cells (labelling index) was normal at birth (dystrophic 8%, control 8.4%), fell to 2.2% in dystrophics and 4.7% in controls at 7 days, and in adults was 0.4% in dystrophics and < 0.1% in controls. It was calculated that even at the observed slower rate of proliferation, the Schwann cell population of the dystrophic L5 ventral root could have risen to that of the normal root by about the 12th postnatal day. It is suggested that in the dystrophic L5 ventral root from birth to 3 weeks of age the Schwann cell production is balanced by an equivalent cell loss.     

ATYPICAL AXON-SCHWANN CELL RELATIONSHIPS IN THE COMMON PERONEAL NERVE OF THE DYSTROPHIC MOUSE: AN ULTRASTRUCTURAL STUDY

Abstracts Jaros E. & Bradley W.G. (1979) Neuropathology and Applied Neurobiology 5, 133–147
Atypical axon-Schwann cell relationships in the common peroneal nerve of the dystrophic mouse: an ultrastructural study
Several atypical features of myelination of the peripheral nervous system are reported in common peroneal nerve of dystrophic mice (129 Re J dy/dy): ( i ) central nervous system-like contact between myelin sheaths of adjacent nerve fibres; ( ii ) nodes and internodes of myelinated fibres enwrapped with cytoplasmic processes of Schwann cells from adjacent nerve fibres; ( iii ) Schwann cells of adjacent nerve fibres co-operating in formation of a single myelin sheath; and ( iv ) a single Schwann cell myelinating two separate axons. In view of the presence of similar features of myelination in the central nervous system, where the myelin producing cells lack basement membrane, we suggest that in the dystrophic peripheral nerves the development of these features can be attributed to the partial deficiency of the Schwann cell basement membrane. Two types of widened nodes of Ranvier are also identified: ( i ) nodes with paranodal damage; and ( ii ) nodes without paranodal damage. In addition, abnormal features of myelination are described which are likely to represent altered Schwann celliaxon relationships during demyelination and remyelination and/or decreased myelinating ability of Schwann cells. We interpret these findings as indicating a metabolic disorder of Schwann cells. They provide an experimental model for the investigation of factors involved in the origin and maintenance of the structural organization of peripheral nerve.     

The cytokine network of Wallerian degeneration: IL-10 and GM-CSF

Wallerian degeneration (WD) is the inflammatory response of peripheral nerves to injury. Evidence is provided that granulocyte macrophage colony stimulating factor (GM-CSF) contributes to the initiation and progression of WD by activating macrophages and Schwann, whereas IL-10 down-regulates WD by inhibiting GM-CSF production. A significant role of activated macrophages and Schwann for future regeneration is myelin removal by phagocytosis and degradation. We studied the timing and magnitude of GM-CSF and IL-10 production, macrophage and Schwann activation, and myelin degradation in C57BL/6NHSD and C57BL/6-WLD/OLA/NHSD mice that display normal rapid-WD and abnormal slow-WD, respectively. We observed the following events in rapid-WD. The onset of GM-CSF production is within 5 h after injury. Production is steadily augmented during the first 3 days, but is attenuated thereafter. The onset of production of the macrophage and Schwann activation marker Galectin-3/MAC-2 succeeds that of GM-CSF. Galectin-3/MAC-2 production is up-regulated during the first 6 days, but is down-regulated thereafter. The onset of myelin degradation succeeds that of Galectin-3/MAC-2, and is almost complete within 1 week. IL-10 production displays two phases. An immediate low followed by a high that begins on the fourth day, reaching highest levels on the seventh. The timing and magnitude of GM-CSF production thus enable the rapid activation of macrophages and Schwann that consequently phagocytose and degrade myelin. The timing and magnitude of IL-10 production suggest a role in down-regulating WD after myelin is removed. In contrast, slow-WD nerves produce low inefficient levels of GM-CSF and IL-10 throughout. Therefore, deficient IL-10 levels cannot account for inefficient GM-CSF production, whereas deficient GM-CSF levels may account, in part, for slow-WD.     

6-Aminonicotinamide selectively causes necrosis in reactive astroglia cells in vivo. Preliminary morphological observations

6-Aminonicotinamide (6-AN) is a potent antimetabolite of nicotinamide. Previous studies show a selective gliotoxic effect of 6-AN in nontraumatized nervous system. The present study was undertaken to determine if 6-AN can be selectively toxic against reactive (vs. nonreactive) glial cells distal to site of crush in rat optic nerve. Previously conducted studies indicate that glial cells in crushed optic nerves undergo marked biochemical changes during the second post-operative week. In the present study, 6-AN was administered by i.p. injection 5 days after right optic nerve crush in doses of either 5 or 10 mg/kg body weight. Rats were killed 2 days after injection. High doses of 6-AN resulted in loss of astrocytes and intracellular glial edema in both crushed and unoperated optic nerve. Results were more dramatic in traumatized nerve. Low doses caused degenerative glial changes in reactive, but not in unoperated optic nerve. Injection of 5 mg doses of 6-AN at 13 days post-operatively caused degeneration of reactive astrocytes. The possibility of using 6-AN to selectively kill highly metabolic reactive astrocytes after CNS injury is discussed.     

Contribution of axonal transport to the renewal of myelin phospholipids in peripheral nerves. I. Quantitative radioautographic study

Kinetics of phospholipid constituents transferred from the axon to the myelin sheath were studied in the oculomotor nerve (OMN) and the ciliary ganglion (CG) of chicken. Axons of the OMN were loaded with transported phospholipids after an intracerebral injection of [2-3H]glycerol or [3H]labeled choline. Quantitative electron microscope radioautography revealed that labeled lipids were transported in the axons mainly associated with the smooth endoplasmic reticulum. Simultaneously, the labeling of the myelin sheath was found in the Schmidt-Lanterman clefts and the inner myelin layers. The outer Schwann cell cytoplasm and the outer myelin layers contained some label with [methyl-3H]choline, but virtually none with [2-3H]glycerol. With time the radioactive lipids were redistributed throughout and along the whole myelin sheath. Since [2-3H]glycerol incorporated into phospholipids is practically not re-utilized, the occurrence of label in myelin results from a translocation of entire phospholipid molecules and from their preferential insertion into Schmidt-Lanterman clefts. In this way, the axon-myelin transfer of phospholipid contributes rapidly to the renewal of a limited pool of phospholipids in the inner myelin layers. When [methyl-3H]choline was used as precursor of phospholipids, the rapid appearance of the label in the inner myelin layers was interpreted also as an axon-myelin transfer of labeled phospholipids. However, the additional labeling of the outer Schwann cell cytoplasm adjacent to Schmidt-Lanterman clefts and of the outer myelin layers reflects a local re-incorporation of the base released from the axon. By these two processes, the axon contributes to purvey the inner myelin layers with new phospholipids and the Schwann cells with new choline molecules.     

Postnatal Schwann cell proliferation but not myelination is strictly and uniquely dependent on cyclin-dependent kinase 4 (cdk4)

Peripheral myelin formation depends on axonal signals that tightly control proliferation and differentiation of the associated Schwann cells. Here we demonstrate that the molecular program controlling proliferation of Schwann cells switches at birth. We have analyzed the requirements for three members of the cyclin-dependent kinase (cdk) family in Schwann cells using cdk-deficient mice. Mice lacking cdk4 showed a drastic decrease in the proliferation rate of Schwann cells at postnatal days 2 and 5, but proliferation was unaffected at embryonic day 18. In contrast, ablation of cdk2 and cdk6 had no significant influence on postnatal Schwann cell proliferation. Taken together, these findings indicate that postnatal Schwann cell proliferation is uniquely controlled by cdk4. Despite the lack of the postnatal wave of Schwann cell proliferation, axons were normally myelinated in adult cdk4-deficient sciatic nerves. Following nerve injury, Schwann cells lacking cdk4 were unable to re-enter the cell cycle, while Schwann cells deficient in cdk2 or cdk6 displayed proliferation rates comparable to controls. We did not observe compensatory effects such as elevated cdk4 levels in uninjured or injured nerves of cdk2 or cdk6-deficient mice. Our data demonstrate that prenatal and postnatal Schwann cell proliferation are driven by distinct molecular cues, and that postnatal proliferation is not a prerequisite for the generation of Schwann cell numbers adequate for correct myelination.     

IMMUNOCYTOCHEMICAL STUDY OF P0 GLYCOPROTEIN, P1 AND P2 BASIC PROTEINS, AND MYELIN-ASSOCIATED GLYCOPROTEIN (MAG) IN LESIONS OF IDIOPATHIC POLYNEURITIS

To investigate the mechanism of myelin breakdown in idiopathic polyneuritis, paraffin and Epon sections of lesions were immunostained with antisera to four proteins in myelin sheaths. Three of these (P0, P2, and BP) are constituents of compact myelin whereas myelin-associated glycoprotein (MAG) is restricted to membranes near Schwann cell cytoplasm in periaxonal and paranodal regions and in Schmidt-Lanterman clefts. In early lesions, there were focal abnormalities in P2, P0, and BP immunostaining of paranodal and internodal myelin. No single protein was affected selectively and lesions occurred in fibres of all sizes, not just in larger fibres selectively stained by P2 antiserum. Early changes in MAG immunostaining occurred only in regions where myelin immunostaining also was abnormal. More severe, late changes in the distribution of P0, P2, and BP and MAG were consistent with the sequence of myelinated fibre alterations seen in segmental demyelination and Wallerian degeneration. In regenerating fibres, MAG antiserum stained periaxonal regions intensely; thin regenerating myelin sheaths were stained by P0, and BP antisera, but not by P2 antiserum. The results show that myelin sheath changes are identified more easily in immunostained sections than in conventional histological preparations. Our data also suggest that in idiopathic neuritis, myelin sheaths are the primary target and that the breakdown of myelin and its proteins is not secondary to Schwann cell damage.     

Changes in peripheral nerves of rats four months after induction of streptozotocin diabetes

Summary Eight streptozotocin-injected Wistar rats and eight controls were fixed by whole-body perfusion 4 months after beginning of the experiment, the nervus radialis was dissected and processed for light and electron microscopy. After light-microscopic study standard photographs of nerve cross sections were measured by means of a semiautomatic image analyzer. The following measurements were obtained: (1) surface of fibres, axons, and myelin sheaths, (2) ratio of myelin to axon surface, and (3) percent of endoneural space. Group means and standard deviations were calculated, and cumulated size class distributions were made. Representative nerve specimens from all animals were also studied by electron microscopy. The quantitative study revealed in the diabetics a severe reduction of the average myelin surface, a mild increase of axonal cross section and of endoneural space, a reduction of myelin/axon ratio and a mild reduction in cross section of the nerve. Ultrastructural lesions of minor degree were found in the cytoplasm of Schwann and mesenchymal cells, no lesion was observed in axons. These findings demonstrate the presence of neuropathy 4 months after induction of diabetes and support the pathogenetic role of the Schwann cell in our experimental model.Supported by the Schweizer Nationalfonds grants nos. 3.198-0.77 and 3.552-0.79     

Nerve fibres in spinal cord impact injuries. Part 1. Changes in the myelin sheath during the initial 5 weeks

The spinal cords of cats were subjected to an impact injury using a "weight dropping" technique and sequential changes in the sheaths of non-degenerate myelinated fibres studied over a 3-week period. By 1 1/2 h after impact fibres showed retraction of some lateral loops from one paranode. The extent and severity of this change increased over the first week so that partial and full thickness demyelination were seen frequently. Partial demyelination most commonly resulted from the internodal termination of the innermost lamellae at an internodal location often associated with a Schmidt-Lantermann incisure. Remyelination by both Schwann cells and oligodendroglia occurred at the end of the second week. Oligodendroglial myelin showed many features of immaturity, similar to those found during development. It is suggested that the very earliest myelin damage is mechanical but is aggravated by other factor(s) one of which is probably ischaemia. Within the most severely injured areas there is death of oligodendroglia and any surviving axons are remyelinated principally by Schwann cells. In intermediate and minimally damaged areas of white matter oligodendroglial remyelination predominates.