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Differential survival of isolated portions of crayfish axons.

Electron microscopic studies show that transplanted segments of sensory axons of varying lengths degenerate within 7-14 days whereas transplanted segments of crustacean motor axons survive morphologically intact for 20-30 days. The middle portion of an isolated motor axon segment degenerates less rapidly than portions of the same axon located nearer the periphery or nearer the ventral nerve cord. One week after transplantation, glial cells appear to phagocytize sensory axons whereas glial cells around motor axons appear to hypertrophy and to have more rough endoplasmic reticulum. After three weeks, motor axons also appear to be phagocytized by glial cells. These data suggest that the glia surrounding isolated motor axons can change from a supportive to a destructive function, whereas glial cells surrounding severed sensory axons primarily have a destructive function. These and other data also indicate that crustacean motor axons receive significant trophic inputs from their own perikaryon, from post-synaptic contacts, and from adjacent glial cells. The possibility that adjacent healthy cells may supply metabolically deficient cells with needed substances could be a significant adaptive advantage for the evolution of multicellular organisms.

Animals↗

Axon regeneration across the site of injury in the optic nerve of the newt Triturus pyrrhogaster.

The process by which axons regenerate following a freeze injury to the optic nerve of the newt was analyzed by light and electron microscopy. Freezing destroys cellular constituents in a one millimeter segment of the nerve, leaving intact the basal lamina and the blood supply to the eye. No axons are seen at the site of injury one to seven days post lesion. This contrasts with the persistence of normal-appearing but severed unmyelinated axons within the cranial stump which thus give a false appearance of early regeneration. The first axon sprouts traverse the lesion and enter the cranial strump by ten days. The number of regenerating axons increases rapidly thereafter with no signs of random growth at the site of injury. These axon sprouts tend to be somewhat larger than normal unmyelinated axons and contain dense core vesicles and abnormal organelles similar to those in growing axons in tissue culture. The persisting basal lamina inside the optic sheath appears to provide continuity across the site of injury, to orient axon sprouts, and to favor an orderly process of axon regeneration without neuroma formation.

Animals↗

Conduction velocity groupings among axons of cat retinal ganglion cells, and their relationship to retinal topography.

Three unresolved issues in the conduction velocity groupings among the axons of cat retinal ganglion cells have been investigated. These are (i) the degree of separation of the velocity ranges of the axons of X-and W-type ganglion cells; (ii) the question whether the velocities of X-and Y-cell axons (i.e. of t1 and t2 axons have faster velocities than contralaterally projecting axons. Evidence is presented that the velocity ranges of W- and X-cell axons are almost completely separate; that the velocities of X- and Y-cell axons are not graded with retinal eccentricity (except in the immediate vicinity of the area centralis) and that ipsilaterally projecting axons are not faster conducting that contralaterally projecting axons. These results provide a context for summarising present understanding of conduction velocity groupings among the axons of cat retinal ganglion cells.

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Greater number of microtubules per axon of unmyelinated fibers of mutant quails deficient in neurofilaments: possible compensation for the absence of neurofilaments.

Morphometric evaluations were performed on the peroneal nerve from mutant quails deficient in neurofilaments (NF) to elucidate the effect of an absence of NF on unmyelinated axons. The diameter frequency distribution of unmyelinated axons was similar between controls and mutants. The mean transverse axonal area, axonal circumference and circularity index of the unmyelinated axons were also similar in controls and mutants. However, the number of microtubules (MT) per axon was greater (P < 0.01) in the mutants than in the controls. The regression analysis relating the number of MT per axon to the diameter of unmyelinated axons indicated a greater number of MT in the mutants than in the controls (P < 0.05-0.01). A significantly greater number of MT per axon in the mutants may suggest a compensatory increase of MT in the absence of NF. This may conserve the size and transverse circular profile of the unmyelinated axons which are probably maintained by both MT and NF in the controls. The number of MT may be increased at the expense of the soluble fraction of tubulin.

Animals↗

Selective retrograde axonal transport of free glycine in identified neurons of Aplysia.

The specific retrograde axonal transport of free glycine within the identified neurons R3-14 of Aplysia californica was studied. The soma of the R3-14 neurons are located in the parietovisceral ganglion and their axons project down the branchial nerve to end in a large peripheral field. Using a double-chambered apparatus, the peripheral tissue was incubated in medium containing a 3H-amino acid for 4-48 hr, while the nerve and ganglion were isolated and perfused with plain or chemically altered medium. The nerve and ganglion were then either rapidly frozen for scintillation counting or fixed for autoradiography. When 3H-glycine was used, radioactivity entered the nerve rapidly, reached the ganglion in 3 hr, and was transported largely (greater than 80%) in the free amino acid form [trichloroacetic acid (TCA) soluble]. The right parietovisceral hemiganglion accumulated up to nine times more radioactivity than the left hemiganglion, reflecting the presence of the R3-14 axons and soma. Two phases of radioactivity were observed, a fast component moving at about 3 mm/hr and a slower (but larger) component moving at about 0.4 mm/hr. Light microscope autoradiography on nerves containing 3H-glycine revealed that the R3-14 axons accounted for more than 30% of the total label in the nerve but occupied less than 7% of the total cross-sectional area of the axonal core. Electron microscope autoradiography showed a close association of silver grains and dense core vesicles in the R3-14 axons. Retrograde axonal transport of free glycine was inhibited by (in decreasing order of effectiveness) mercuric chloride, vinblastine, colchicine, Nocodazole, and 2,4-dinitrophenol (2,4-DNP). Comparative studies of other amino acids [3H-leucine, 3H-serine, 3H-glutamic acid, 3H-gamma-aminobutyric acid (3H-GABA), and 3H-alanine] showed that 3H-glycine is the only amino acid that is rapidly axonally transported in large quantities within the R3-14 axons. This work demonstrates, for the first time, that a free amino acid, glycine, is transported in the retrograde direction within a select group of axons. The significance of this transport of glycine is discussed in relation to its use as a neural messenger by neurons R3-14.

2,4-Dinitrophenol↗

Irregular geometries in normal unmyelinated axons: a 3D serial EM analysis.

Axons have generally been represented as straight cylinders. It is not at all uncommon for anatomists to take single cross-sections of an axonal bundle, and from the axonal diameter compute expected conduction velocities. This assumes that each cross-section represents a slice through a perfect cylinder. We have examined the three-dimensional geometry of 98 central and peripheral unmyelinated axons, using computer-assisted serial electron microscopy. These reconstructions reveal that virtually all unmyelinated axons have highly irregular axial shapes consisting of periodic varicosities. The varicosities were, without exception, filled with membranous organelles frequently including mitochondria, and have obligatory volumes similar to that described in other neurites. The mitochondria make contact with microtubules, while the other membraneous organelles were frequently found free floating in the cytoplasm. We conclude that unmyelinated axons are fundamentally varicose structures created by the presence of organelles, and that an axon's calibre is dynamic in both space and time. These irregular axonal geometries raise serious doubts about standard two dimensional morphometric analysis and suggest that electrical properties may be more heterogeneous than expected from single section data. These results also suggest that the total number of microtubules contained in an axon, rather than its single section diameter, may prove to be a more accurate predictor of properties such as conduction velocity. Finally, these results offer an explanation for a number of pathological changes that have been described in unmyelinated axons.

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Reorganization of intrinsic components in the distal motor axon during outgrowth.

We have studied the changes in the distribution of three intrinsic axonal components during the growth and maturation of sprouts in vivo. Neurofilaments, tubulin and synaptophysin, a synaptic vesicle protein, were visualized in motor axons and their sprouts using immunocytochemical staining of frozen longitudinal sections of muscle. We examined changes in these elements in sprouts regenerating after axonal crush injury and in those evoked from intact axons by denervation changes in muscle. Our results show that intrinsic axonal components move into newly formed motor axon sprouts in different temporal patterns. Based on the patterns of reorganization of staining of intrinsic axonal components, two types of outgrowth can be distinguished. One type, synaptic elaboration, is manifest by short, broad axonal processes that produce enlargement of the synaptic zone (synaptophysin staining) with little change in the distribution of intrinsic cytoskeletal elements. A second type of outgrowth, axonal elongation, occurs during axonal regeneration and ultraterminal sprouting and is longitudinal in form. In these sprouts there is a sequential appearance of neurofilament and then, several days later, tubulin immunostaining. Synaptophysin only accumulates in these sprouts after two weeks at points of synaptic contact with a muscle fibre.

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Double myelination of axons in the sympathetic nervous system of the mouse. I. Ultrastructural features and distribution.

This study has examined the structural features and distribution of 'doubly myelinated' axons in normal adult and aged mice. Investigation focused on the superior cervical ganglion (SCG) and paravertebral sympathetic ganglia, which were extensively serial-sectioned for light and electron microscopy. In the SCG, the principal features of doubly myelinated regions were that an apparently normal myelinated axon was enclosed for part of its length by an additional (outer) myelinating Schwann cell. The separate nature of the inner and outer Schwann cells was emphasized by the consistent presence of individual nuclei in each, and by the presence of endoneurial space, often containing collagen fibrils, between the inner and outer cells. In some cases more than a single outer Schwann cell was present, arranged serially along the inner myelinated fibre. While double myelination forms through a mechanism involving displacement of an original myelinating Schwann cell by an interposed Schwann cell (see companion paper), we here provide evidence that in some instances the outer Schwann cell fails to retain any direct axonal contact, either with the axon centrally enclosed within the configuration or with any neighbouring axon. In contrast to the rat, delicate cytoplasmic processes often extended from the lateral extremes of outer Schwann cells. However, again no evidence for axonal contact was found, and similar processes also extended from the paranodal region of some singly myelinated non-displaced Schwann cells. Without exception the outer myelin sheath remained structurally intact, and characteristically underwent a series of conformational changes (progressive infolding of the paranodes and new areas of myelin compaction) which infer a continuing capacity of the outer Schwann cell to translocate myelin-specific components in a co-ordinated manner. A basal lamina was always present on the 'abaxonal' plasma membrane of the outer cell, but not on the 'adaxonal' surface except in areas involved in infolding, thus retaining the polarity which existed at the time of displacement from the axon. At single cross-sectional levels through the SCG, up to approximately 4% of myelinated axons were involved in double myelination. Double myelination was not detected in the sciatic nerve or in the paravertebral ganglia, thus indicating a predilection for the SCG as a site of development of these configurations. Though not challenging the role of the axon in initiating the formation of myelin, these data indicate that in this tissue myelin maintenance does not require direct contact between axonal and Schwann cell plasma membranes.

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Double myelination of axons in the sympathetic nervous system of the mouse. II. Mechanisms of formation.

The phenomenon termed 'double myelination', present in sympathetic nerve of normal adult rats and mice, comprises regions of a myelinated axon which are concentrically ensheathed by additional (outer) myelinating Schwann cells. Evidence has been presented that in some instances the outer Schwann cell fails to make contact with an axon, yet its myelin sheath characteristically remains ultrastructurally intact. The present study has sought to identify and analyse configurations intermediate between single and double myelination, in order to determine the mechanism(s) underlying the formation of double ensheathment. Superior cervical ganglia from normal male mice aged 12-24 months were prepared for electron microscopy by systemic aldehyde perfusion. Regions of interest were extensively serial-sectioned for detailed electron microscopical analysis and reconstruction. The earliest evidence for alteration to the expected intimate ensheathment of axons by myelinating Schwann cells involved invasion of supernumerary Schwann cells and their processes at the node of Ranvier, resulting in displacement of the paranodal pockets from axonal contact. Similar paranodal displacement occurred at heminodes as a result of lateral extension and invasion of processes from the adjacent Schwann cell (i.e. the cell investing the unmyelinated domain of the axon). Subsequently, processes of the invading cell extended progressively into internodal regions, located at all times between the plasma membranes of the axon and displaced Schwann cell. The cytoplasmic pockets at the remaining paranode were then subject to invasion. At various stages of displacement myelin formation commenced within the invading cell, representing the first acquisition of double myelin ensheathment in the development of the configuration. Involvement of haematogenous cells in displacement was not detected. There was also evidence consistent with paranodal displacement by adjacent pre-existing myelinating cells, but this additional mechanism appeared minor relative to the involvement of (initially) non-myelinating Schwann cells. We found no evidence for the alternative possibility that Schwann cells could synthesize a myelin sheath around a pre-existing myelinated axon de novo, independent of any direct axonal contact. These results are consistent with the well-established requirement for axonal contact by Schwann cells engaging in initial myelin formation, in the sense that the myelin sheath of the outer cell was synthesized prior to its displacement, and that a myelin sheath was not formed by the invading cell until it had invested the axon in a 1:1 relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

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Magnetic stimulation of axons in a nerve bundle: effects of current redistribution in the bundle.

Recently, we developed a model of magnetic stimulation of a concentric axon in an anisotropic nerve bundle. In that earlier paper, we considered a single axon surrounded by a nerve bundle represented as a homogeneous anisotropic monodomain medium. In this paper we extend our previous calculations to examine excitation of axons within a nerve bundle without neglecting the presence of other axons in the nerve bundle. A three-dimensional axial symmetry volume conductor model is used to determine the transmembrane potential response along an axon due to induced electric fields produced by a toroidal coil. Our principal objective is to examine the effect of current redistribution to other axons in the bundle on excitation characteristics. We derive the transmembrane potential along an axon for two currently available models of current redistribution: the biodomain model and the spatial--frequency monodomain model. Results indicate that a reduction in the transmembrane potential along an axon due to the presence of other nerve fibers in the bundle is observed. Axons located at the periphery of a nerve bundle have lower thresholds and different excitation sites compared with axons located near the center of a nerve bundle.

Axons↗

Characterization of a prolonged regenerative attempt by diffusely injured axons following traumatic brain injury in adult cat: a light and electron microscopic immunocytochemical study.

Traumatic brain injury in animals and humans is well known to cause axonal damage diffusely scattered throughout the brain without evidence of other brain parenchymal change. This observation has prompted some to posit that such damaged axons are well positioned to mount a regenerative attempt. The present study uses an immunocytochemical marker specific for regenerating neurites to explore this issue. Further, in an attempt to expedite and enhance any potential regenerative effort, this study evaluates the efficacy of intrathecally applied nerve growth factor. Three sets of experiments were performed in adult cats. One group of animals was subjected to moderate fluid percussion brain injury and followed for 7 or 14 days post injury, with the continuous intraventricular infusion of nerve growth factor delivered by implanted osmotic pumps. These animals were compared to a second group of time-matched, sham-operated animals receiving artificial cerebrospinal fluid infusion. To assess axonal damage immunohistochemical staining for the low molecular weight neurofilament subunit (NF-L) was carried out using an NR4 monoclonal antibody. To localize axons exhibiting a regenerative response immunohistochemical staining for the growth associated protein GAP43 was employed. In sham controls, at the light microscopic level NF-L-immunoreactive axonal swellings were numerous at 7 days, but by 14 days post injury their frequency declined markedly. In contrast, GAP43-immunoreactive, disconnected reactive axonal swellings were rarely observed at 7 days but were numerous at 14 days. Ultrastructural analysis at 14 days post injury of carefully matched sections revealed reactive axons demonstrating sprouting consistent with a regenerative effort. Analysis of tissue from animals of 14 days of survival indicated that supplementation with nerve growth factor did not appear to enhance the capacity of damaged brain axons to mount a regenerative attempt. Rather, it appears that regenerative efforts seen reflect a spontaneous response. A third group of adult cats, subjected to the same injury but not subjected to osmotic pump implantation, was allowed to survive for 22-28 days. Animals in this group also demonstrated GAP43 immunoreactivity in reactive axonal swellings in the brain stem. This study demonstrates that diffusely injured axons can mount a sustained regenerative attempt that is associated with a reorganization of their cytoskeleton and accompanied by an up-regulation of growth-associated proteins.

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Odorant receptor proteins in olfactory axons and in cells of the cribriform mesenchyme may contribute to fasciculation and sorting of nerve fibers.

Odorant receptors (ORs) have been shown to be present not only in the chemosensory cilia of the olfactory sensory neurons, but also in their axon terminals. This observation has emphasized the notion that the receptor protein may contribute to the precise receptor-specific targeting of olfactory axons in the olfactory bulb. This concept implies a particularly important role for the axonal receptor protein during the onset and early phase of the wiring process during development. In the present study, we have demonstrated, by means of specific antibodies, that, as early as mouse embryonic day E12, the OR protein can be visualized in outgrowing axonal processes of the olfactory epithelium and in cells located in the cribriform mesenchyme. On their trajectory from the olfactory epithelium through the cribriform mesenchyme toward the forebrain, axons with strong OR immunoreactivity have only been seen in the dorsal part of the mesenchyme where they traverse the region of OR-positive cells. Upon visualization by specific antibodies, these cells have been revealed to have long protrusions extending along the surface of nerve fascicles. They are often located at bifurcations where two small axon fascicles merge to form a stronger bundle. Within this region, fascicles coalesce forming a coherent nerve. Moreover, within the now compact nerve bundle, axons visualized by the OR-specific antibody are no longer distributed evenly but are segregated from other axonal populations within the nerve. These findings suggest that OR proteins in the membrane of axonal processes and of cells in the cribriform mesenchyme are involved in crucial processes such as fasciculation and the sorting of outgrowing axons, both of which are fundamental for the initiation and establishment of the precise wiring of the olfactory system during early development.

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Catecholaminergic axo-axonic synapses in the nucleus of the tractus solitarius (pars commissuralis) of the cat: possible relation to presynaptic regulation of baroreceptor reflexes.

A study was performed on adult cats to investigate synaptic structures of nerve terminals in the commissural portion of the nucleus of the tractus solitarius (NTS); a site where the cardiovascular afferent fibers terminate and where a dense plexus of adrenergic element also resides. Synaptic contacts observed in the commissural portion were predominantly axo-dendritic but a smaller number of axo-somatic synapses were also recognized. A third type of junction, axo-axonic, appears to be unique to the commissural portion of the nucleus, since no axo-axonic contacts were encountered in the medial and ventrolateral portions of the NTS. By labeling with the 'false' neurotransmitter 5-hydroxydopamine (5-OHDA), three types of axo-axonic contacts with different presynaptic components could be identified; namely, axon varicosities with small clear spherical vesicles, axon varicosities containing flat synaptic vesicles and others with small cord vesicles labeled with 5-OHDA. Postsynaptic components were always axon varicosities with clear spherical vesicles. After surgical denervation of the IXth and Xth cranial nerves, no degenerated axon varicosities were observed in the presynaptic side in the axo-axonic contact. The present study clearly demonstrates that the commissural portion of the NTS contains axo-axonic synapses and some of the adrenergic axons in this area provide the presynaptic components for this type of synapse. Possible roles of adrenergic nerves to presynaptic regulation of baroreceptor reflexes are discussed.

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Evidence that 4S RNA is axonally transported in normal and regenerating rat sciatic nerves.

Studies in regenerating goldfish optic nerves indicate that RNA may be axonally transported during optic nerve regeneration14,18,19. The present study was performed to determine if the axonal migration of RNA could be demonstrated during regeneration of the rat sciatic nerve. Rats, which had only the left sciatic nerve crushed 10 days earlier, were injected bilaterally with [3H]uridine into the spinal cord at segmental levels L5 and L6, thus labeling ventral horn cells giving rise to the sciatic nerve. Six, 14 and 20 days later rats were sacrificed by cardiac perfusion of saline followed by 10% formaldehyde. Formaldehyde-precipitable radioactivity, identified as [3H]RNA, was 4--5 times greater in the regenerating sciatic nerve compared to the normal nerve and moved without impediment beyond the point of the crush into the regenerating portion of the nerve. The axonal migration of free unincorporated labeled RNA precursors was also demonstrated, raising the possibility that the distribution of [3H]RNA along the sciatic nerve might be entirely extra-axonal; i.e., free [3H]uridine is taken up by Schwann cells from the axon where it is incorporated into [3H]RNA. This interpretation of the data would also result in the appearance of a proximodistal distribution of RNA associated radioactivity. To determine whether any sciatic nerve [3H]RNA was due to axonal transport, rats which had only the left sciatic nerve crushed 10 days earlier were injected bilaterally with [3H]uridine into the spinal cord. Fourteen days after injection, rats were sacrificed and radioactivity present in the nerve was confirmed as RNA by SDS polyacrylamide gel electrophoresis. Radioactivity in the various RNA species 14 days after intraspinal injection showed the following distribution: 28 + 18S RNA--normal 39.3% +/- 2.1; regenerating 45.4% +/- 1.6; 4S RNA--normal 43.0% +/- 1.3; regenerating 46.8% +/- 2.7. Similar characterization of sciatic nerve RNA 1 or 3 days following the intravenous administration of [3H]uridine gave the following distribution: 28 + 18S RNA--normal 72.4% +/- 3.0; regenerating 75.0% +/- 3.6; 4S RNA--normal 7.7% +/- 1.3; regenerating 10.7% +/- 0.8. The intraspinal injection of [3H]uridine would label Schwann cell RNA and, in addition, any species of intra-axonal RNA, while intravenous injections would label Schwann cell RNA and not axonal RNA. If 4S RNA is in the axon, one would predict relatively more labeled 4S RNA following intraspinal injections than following intravenous injections. The data demonstrate an enrichment of 4S RNA in both normal and regenerating rat sciatic nerve following the intraspinal but not following the intravenous injection of labeled precursor. Therefore, we suggest that 4S RNA migrates axonally in both normal and regenerating sciatic nerves of rats.

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Age related sprouting of dorsal root axons after sensory denervation.

To test for sprouting of dorsal root axons, 3 consecutive dorsal roots were sectioned above and 3 were sectioned below a spared root in rats 1 month and 24 months old. At various survival times, myelinated and unmyelinated axons were counted in the spared root, the first cranial root and the first caudal root, and these counts were compared to similar counts from the same roots on the unoperated side. The counts of myelinated axons in all roots and of unmyelinated axons in the caudal roots were not different from the counts in the same roots on the unoperated side. Thus there is no evidence for sprouting of these axons in our system. By contrast, the unmyelinated axons in the cranial and spared roots were significantly increased as compared to the unmyelinated axons in the same roots on the unoperated side. We interpret this increase to be sprouting of dorsal root axons. To determine the effects of age, animals operated at 1 month and sacrificed 1 month, 3 months or 18 months later were compared with animals operated at 2 years and sacrificed 1 month later. The unmyelinated axons were greater by approximately 20% on the operated side in the cranial and spared roots in the young rats and by approximately 8% in old rats. Thus the sprouting of unmyelinated axons is more vigorous when the surgery is performed in young animals, but there still seems to be a response in older animals.

Aging↗

A comparison of axonal numbers in dorsal roots following spinal cord hemisection in neonate and adult rats.

This study presents myelinated and unmyelinated axon counts from thoracic dorsal roots of rats whose spinal cords were hemisected at birth or at 1 year of age. Axonal numbers from a root on the unoperated side are compared to numbers from the root of the same segment on the operated side of the animal. Counts were made 3 segments cranially and 3 segments caudally from the hemisection. In animals hemisected at birth and sacrificed at 3-8 months, there is a statistically significant increase in unmyelinated axons in roots of the operated as compared to the normal side. We interpret this as sprouting of unmyelinated axons. In animals hemisected at 1 year of age, the statistically significant change was a drop in myelinated axons in roots of the operated side. We interpret this as a loss of myelinated axon cell bodies due to axon section in the dorsal funiculus. Thus axonal sprouting occurs in young rats in our paradigm and a loss of myelinated axons occurs in older animals. We emphasize that different axonal populations respond to hemisection in different ways at different times.

Age Factors↗

The relationship between axon diameter, myelin thickness and conduction velocity during atrophy of mammalian peripheral nerves.

The atrophy of cutaneous (sural) and muscle (medial gastrocnemius) nerves proximal to a ligation were studied in cats for periods up to 9 months, using light and electron microscopy, conduction velocity measurements and computer simulations. As atrophy proceeds, nerve fibres become increasingly non-circular. Cross-sectional areas of axons and fibres (axon + myelin) were measured. The diameters of equivalent circles (having the same axon and fibre cross-sectional area) were then calculated. A linear relation was found between axon diameter and fibre diameter, but the slope decreased as atrophy continued. This indicates that the axon cross-sectional area decreases relatively more than the total fibre area. Reduction in conduction velocity correlates more closely with reduction in axon diameter than fibre (axon + myelin) diameter. The ratio of the inner (axon) perimeter to the outer (myelin) perimeter remains constant at or near the optimal value of 0.6 for conduction in all groups of fibres at all periods of atrophy. Furthermore, the thickness of the myelin remains constant for a given perimeter over the entire period of atrophy studied. This suggests that the number of turns of myelin and the length of each turn remain unchanged during peripheral nerve atrophy. A simple geometric model explains how this can occur without gaps developing between the axon and myelin or between the turns of myelin. The Frankenhaeuser-Huxley equations for conduction in myelinated nerve fibres predict changes in conduction velocity similar to those observed, if the axons atrophy without changes in myelin. The advantages of this mode of atrophy are discussed.

Animals↗

The effect of a conditioning lesion on the regeneration rate of peripheral nerve axons containing substance P.

The regeneration rate of peripheral nerve axons containing substance P-like immunoreactivity (SPLI) was measured in rat sciatic nerve by radioimmunoassay of SPLI in nerve segments 2, 4 and 6 days after a test lesion made by briefly crushing the nerve at the hip. The regeneration rate of the fastest growing sensory axons was also measured in the same nerves using the pinch-reflex procedure. Three groups of animals were compared: group S, which received only the single test lesion, had regeneration rates of 3.57 +/- 0.26 (S.E.) mm/day for SPLI-containing axons and 3.53 +/- 0.14 mm/day for the fastest growing sensory axons. Group A/H, which received a conditioning lesion on the tibial nerve at the ankle 7 days prior to the test lesion at the hip, had a regeneration rate for SPLI-containing axons which was not significantly different from group S, of 3.35 +/- 0.17 mm/day. However, the regeneration rate for the sensory axons was significantly increased to 4.60 +/- 0.23 mm/day. Group H/H, which received both conditioning and test lesions at the hip, once again separated by 7 days, showed a significant increase in regeneration rate of SPLI-containing axons to 5.50 +/- 0.33 mm/day and a further increase over group A/H in the regeneration rate of sensory axons to 6.70 +/- 0.25 mm/day. We conclude that the small-diameter, unmyelinated axons containing SPLI in peripheral nerve normally regenerate at the same rate as the fastest growing sensory axons.(ABSTRACT TRUNCATED AT 250 WORDS)

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