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Biomedical subjects

R L Friede

Publications and source records attributed to R L Friede.

At least 55 records · Page 3Linked to original sources

A quantitative assessment of myelin sheaths in the peripheral nerves of dystrophic, quaking, and trembler mutants.

If myelin sheaths are relatively thin for axon caliber, this is generally taken as a sign of insufficient myelin formation. However, recent studies have shown that sheath thickness relates not only to axon caliber; the relative length of the internode is also important. Foreshortened internodes have slightly thinner sheaths than long internodes of the same fiber caliber (Friede and Bischhausen 1982). In the present study we compared sheath thickness with internode geometry in the sciatic fibers of three murine mutants, the Dystrophic, Quaking and Trembler mice, using a new computer-assisted method. A quantitative correspondence was found between abnormally thin sheaths and internode foreshortening. The magnitude of the changes was the same as that found previously in normal and regenerated fiber populations. The data show that the geometric proportions of internodes cannot be ignored when assessing sheath thickness, and they also shed some new light on the mechanisms which produce abnormally thin sheaths.

Animals↗

Extradural spinal angiolipoma with secretory activity. An ultrastructural, clinico-pathological study.

The light and ultrastructural analyses of an extradural intraspinal angiolipoma causing symptoms of spinal cord compression, are reported. The tumour showed morphological evidence of an endocrine-like secretory activity of fat cells, with an apparent mechanism of secretory function that has not previously been described for angiolipomas. The secretory granules, containing a lipid-like material, were covered with a continuous basement membrane originating from the basement membrane of the adipocyte.

Exocytosis↗

The axon tree of rat motor fibres: morphometry and fine structure.

A quantitative light and electron microscopic study of the axon tree of rat motor fibres was undertaken to supply data relevant to the understanding of the spread of excitation. Continuous proximodistal foreshortening of internode length and dwindling of fibre calibre were statistically verified. Internodes had progressively foreshortened geometric proportions (length/diameter quotient). The postbranching internodes were significantly shorter than would correspond to the general trend, but no such foreshortening was evident for the prebranching internodes. Relative sheath thickness (g-ratio, i.e. quotient axon diameter/fibre diameter) of filial fibres did not differ from the stem. Increase in axon area in filial fibres versus stem fibre averaged 1.3. The total proximodistal increase in axoplasmic area from the stem fibre to the distal branches was less than two since increases at branch points were compensated by the proximodistal dwindling of fibres. Nodal membrane area of branch points was greater than in nonbranching fibres, and there were larger than normal microvillar spaces. The majority of branches were approximately symmetric, but asymmetric branchings were also found. The thinner branches of these had wider nodal gaps than the thick branches. The observed changes were interpreted as adaptations to facilitate uniform spread of excitation along the axon tree; asymmetric branchings, however, may permit routing of impulses.

Animals↗

Effects of cold adaptation and starvation on sciatic nerve fibers in the frog.

The conditions under which frogs are kept prior to experimentation were found to have a measurable effect on peripheral nerve structure. Frogs kept for 12 weeks at 4 degree C had markedly shrunken sciatic nerve fibers compared with frogs kept at 19 degrees C. Intermediate fiber shrinkage was found for frogs kept at 19 degrees C without feeding. Counts of neurofilaments and microtubules showed that fiber shrinkage was from a preferential loss of filaments, indicating cold- or starvation-induced atrophy of the axon's cyto-skeleton. This effect, however, was superimposed with additional osmotic axonal shrinkage, causing filament densities to increase per area. There were no changes in myelin sheath thickness due to cold adaptation or fasting.

Adaptation, Physiological↗

A correlative study of internode proportions and sensitivity to procaine in regenerated frog sciatic nerves.

A comparison of regenerated and normal frog sciatic nerves showed a marked reduction in conduction velocity from 37.5 to 15.2 m/s with little change in the absolute refractory period. Changes in conduction velocity corresponded to a reduced mean axon caliber (4.8 versus 6.6 micron). Regenerated nerves also had markedly foreshortened internodes (mean of 309 versus 1236) micron) and thinner sheaths than controls. The geometric proportions of internode length/fiber caliber (l/d) was reduced to approximately one-third of normal. Regenerated nerves were more easily blocked by exposure to 3 mmol/liter procaine than controls, showing greater increase in the absolute refractory, or decreases, respectively, in the peak of the alpha-wave and the area of the compound action potential; the effect of procaine on conduction velocity was less marked. Exposure of various lengths of nerves in chambers of 1, 3, or 20 mm length revealed greater differences for the shorter chambers. The data indicated that some effects could be attributed to the foreshortening of the regenerated internodes. The main difference between normal and regenerated nerves, however, had to be attributed to changes in the nodal membrane characteristics of the latter.

Action Potentials↗

Millipore diffusion chambers allow dissociation of myelin phagocytosis by non-resident cells and of allogenic nerve graft rejection.

Allogenic graft rejection leads to rapid tissue destruction of nerves transplanted directly into a muscle lodge. If the nerves are enclosed in 5.0 micron pore chambers and transplanted into the peritoneal cavity, there is no allogenic graft rejection. The phagocytosis of myelin by invading cells is, however, not disturbed, showing that these cells can distinguish the degenerating myelin from the Schwann cell without being responsive to the Schwann cell's allotype. If the allografts are allowed to predegenerate for 4 wk in 0.22 micron pore chambers which do not admit any cells, there is a striking mitigation of the allogenic graft rejection if the nerves are subsequently released from the chamber. Myelin phagocytosis in such nerves is also reduced. These observations indicate the existence of a hierarchy of cellular recognition mechanisms involved in nerve tissue degradation. Phagocytosis of the myelin sheath by macrophages involves recognition mechanisms which differ from those of the allogenic rejection of the Schwann cell, presumably mediated by T lymphocytes.

Animals↗

A new approach toward analyzing peripheral nerve fiber populations. I. Variance in sheath thickness corresponds to different geometric proportions of the internodes.

The thickness of the myelin sheath is known to increase with axon caliber, but there is also a superimposed, slight variation in sheath thickness depending on whether a fiber of a given caliber has very long or very short internodes. This relationship between myelin sheath thickness and the geometric proportion of the internode has been shown in subserial sections of isolated nerve fibers. It allows a prediction of sheath thickness from the quotient internode length/axon caliber, or conversely, a prediction of internode foreshortening from sheath thickness. We applied this new approach to the analysis of sciatic fiber populations of frogs, mice, rats and cats. The geometric proportions of these fibers were defined by the quotient internode length/fiber caliber. This quotient was compared with minor variation in sheath thickness as determined with a computer-assisted technique measuring large numbers of fibers in low-power electron micrographs. The method also calculated fiber shrinkage and recalculated all data for circular fiber profiles. The data obtained confirmed previous electron microscopic measurements showing that there is a slight reduction in sheath thickness when a fiber of a given caliber has relatively short internodes, and vice versa. A population of very thin, thinly myelinated fibers was also revealed. Sheath thickness and the geometric proportions of internodes in frogs differed markedly from those in mammals.

Animals↗

A new approach toward analyzing peripheral nerve fiber populations. II. Foreshortening of regenerated internodes corresponds to reduced sheath thickness.

The new approach used in this study is based on the concept that axon caliber is not the only factor affecting the thickness of the myelin sheath. It is necessary to consider the entire geometric proportions of the internode, since sheath thickness corresponds to the relationship between axon caliber and the length of the internode. This type of analysis was applied to the regenerated internodes in rat sciatic nerves. Survival periods of 4, 9, 18 and 36 weeks were studied after lesions had been placed in young adult rats. The data show significantly thinner sheaths for regenerated fibers as compared with normal nerves, consistent with previous observations. This reduction in sheath thickness, however, corresponded quantitatively to the degree of foreshortening of internodes in the regenerated nerves. An average reduction of 10 in the quotient internode length/fiber caliber corresponded to a reduction of about 0.015 in the relative thickness of the sheath (quotient axon diameter/fiber diameter). This means that regenerated myelin sheaths are not truly hypoplastic; rather, they are adapted to the reduced internode length, and have the same relationship found for normal fibers. In partially damaged nerves there was a clear distinction in terms of sheath thickness between regenerated fibers and undamaged fibers. Demonstration of this phenomenon by scatter diagrams opens new possibilities for the quantitative assessment of neuropathies.

Animals↗

A morphometric study of nerve fiber atrophy in rat spinal roots.

A morphometric study of atrophy of nerve fibers was made in the ventral and dorsal roots of rats, four to 48 weeks (wk) after transection of their sciatic nerves and with regeneration prevented. The pathophysiological events of fiber atrophy may be summarized as follows: wasting of the axon caliber coincides with a loss of neurofilaments with relative preservation of microtubules. This leads to non-circularity of the fiber, evident from four wk on. The caliber of the circular profile is also reduced. Adaptive changes in myelin sheath structure follow. Thinner fibers with relatively thick sheaths are first detectable after eight wk and prominent after 24 to 48 wk. This change may indicate passive slippage of the sheath, but sheath remodelling in adjustment to a changed internodal geometry appears more likely.

Animals↗

Combined scatter diagrams of sheath thickness and fibre calibre in human sural nerves: changes with age and neuropathy.

A computer-assisted method permits collection of large numbers of measurements of fibre profiles in electron micrographs of human sural nerve biopsies. The method is based on simultaneous demonstration of fibre calibre and of sheath thickness in terms of the g-ratio (quotient axon diameter/fibre diameter), and on the recalculation of all parameters for circular fibre profiles. The fibres of small and large diameters of human sural nerves were found to form separate populations with distinctly different trends for sheath thickness and also different patterns of maturation. Preliminary data in neuropathy show that this method gives a better distinction of the extent of damage to either of the two populations; it also permits assessment of the number of regenerating or remyelinating fibres.

Adolescent↗

Central spinal myelinolysis.

A midline lesion of the funiculus gracilis was found in four patients with histories of alcoholism, nutritional disturbance, and repeated episodes of electrolyte imbalance. Histologic and anatomic abnormalities were similar to those of central pontine myelinolysis. Sodium imbalance may play a role in the pathogenesis of both conditions.

Adult↗

Changes in myelin sheath thickness and internode geometry in the rabbit phrenic nerve during growth.

The rabbit phrenic nerve was studied at seven phases of growth from the newborn to the adult to determine the length of the nerve fibres, the length of the internodes, the fibre calibre, the geometric proportions of the internodes and the thickness of the myelin sheaths. The elongation of the internodes corresponded precisely to the elongation of the nerve, indicating a constant number of approximately 140 internodes per fibre, each internode elongating commensurate with body growth. Internode elongation was accompanied by increases in fibre calibre, but these parameters did not change in precise proportion. The internodes of thick fibres were relatively short for calibre, as defined by the length/diameter quotient. This trend of foreshortening changed during growth. Sheath thickness, defined by the quotient axon diameter/fibre diameter, was determined with a computer-assisted method. Fibres of young rabbits had relatively thin sheaths for axon calibre, compared with adult rabbits. The changes in sheath thickness corresponded to the changes in internode geometry. This was consistent with previous studies showing that elongation or foreshortening of an internode of a given calibre has a slight, but definite effect on the thickness of its myelin sheath.

Animals↗

Conduction velocity varies with osmotically induced changes of the area of the axon's profile.

The conduction velocity of frog ischiadic nerves incubated in vitro in osmolarities between 220 and 1000 mOsm decreased with the degree of fiber shrinkage. The latter (non-circularity factor) was determined from computer-assisted measurements in freeze-substituted or in chemically fixed fibers. Freeze-substituted normal nerves had a non-circularity factor of 0.91 for fibers of all calibers, which likely reflects the in vivo state of the fiber population. Chemically fixed nerves had a non-circularity factor near 0.68, consistent with previous data. Non-circularity factors decreased with increasing osmolarities of the media, regardless of the type of tissue preparation. Conduction velocity decreased with decreasing non-circularity. Restoration of the nerves to normotonic media increased conduction velocity. The rates of change were accelerated in nerves chemically desheathed with Triton. The decrease in the conduction velocity in osmotically shrunken nerves did not correspond to changes in the absolute refractory period for the propagation of the impulse, used as a sensitive index of non-specific damage. These experimental observations corroborate data from computer simulation of relative sensitivities of nodal and internodal parameters.

Animals↗

Unilateral hydrocephalus from early developmental occlusion of one foramen of Monro.

Unilateral hydrocephalus due to occlusion of one foramen of Monro was found incidentally at necropsy in a 52-year-old man. There was no evidence of a postinflammatory or neoplastic origin of the occlusion. Backward tilting of the diencephalon, asymmetric insertion of the septum pellucidum, lateral tilting of the fornices, and deformation of the hippocampal formation indicated an early developmental origin of the lesion.

Cerebral Ventricles↗

The role of non-resident cells in Wallerian degeneration.

Wallerian degeneration was studied in the phrenic or sciatic nerves of mice following transplantation into Millipore diffusion chambers of 0.22 micron pore size which were implanted in the peritoneal cavity and kept for up to eight weeks. This method positively eliminates the access of nonresident cells to the tissue, at the same time providing proper conditions for tissue survival. Such nerves showed no proliferation of Schwann cells and no evidence for their active role in the removal or digestion of myelin. Schwann cells rejected their sheaths and the latter persisted for weeks, leading either to sheath distension (the sheath becoming wider and thinner) or to collapse (the sheath becoming thicker, collapsing upon the empty axis cylinder). The outer envelope of Schwann cytoplasm separated into pseudopodia rich in microtubules. Sheath rejection led to a slow decay of the myelin in the absence of active phagocytosis. There was profuse fibroblastic proliferation from the epineurium and perineurium, from which cells migrated into the chambers developing fatty change. No evidence was found to link the fatty change in fibroblasts to sheath decay. Diffusion chambers of 5.0 micron pore size were invaded by leukocytes and monocytes. Nerves kept in such chambers showed active phagocytosis of myelin leading to its removal, similar to Wallerian degeneration in situ. Phagocytes were shown to attack selectively the rejected myelin sheaths, distinguishing the latter from the surviving Schwann cells, even though both structures derive from the same cell. The activity of phagocytes in digesting myelin was mediated by a signal which diminished in intensity with time; there was very little active phagocytosis of myelin in nerves that had been predegenerated in 0.22 micron pore chambers. Various modifications of the experiment, including studies with co-cultured peritoneal macrophages or bone marrow, indicate a need for additional activating factors to induce myelin phagocytosis.

Animals↗

Relations between axon length and axon caliber. "Is maximum conduction velocity the factor controlling the evolution of nerve structure"?

A search was made for any existent relationship between the length of a nerve fiber and the caliber of its axon. This was done in the hope of defining morphological parameters useful for assessing conduction time. Four fiber populations were examined: (1) phrenic fibers in rat and rabbit during different phases of body growth; (2) phrenic fibers of mature animals of greatly different body size including mouse and cow; (3) rat intercostal nerves which vary in length by a factor exceeding 5 due to the funnel-shape of the thorax; and (4) ventral root fibers of the cow. In all of these fiber populations, there was no evidence for a direct relationship between the length of a fiber and its caliber. Rather, a tendency was noted for fiber caliber to approach certain ceilings independent of length. These data, seen in conjunction with other information on fiber structure, cast serious doubt on the widely accepted concept that maximum conduction velocity is the factor controlling nerve structure. A much more likely factor controlling the structure of myelinated nerve fibers is the capacity to modulate information by frequency coding of impulses.

Aging↗

Why do bridging veins rupture into the virtual subdural space?

Electron microscopic data on human bridging veins show thin walls of variable thickness, circumferential arrangement of collagen fibres and a lack of outer reinforcement by arachnoid trabecules, all contributory to the subdural portion of the vein being more fragile than its subarachnoid portion. These features explain the laceration of veins and the subdural location of resultant haematomas.

Aged↗