C. Hildebrand

Myelinated nerve fibres in the CNS

(1) Lamellated glial sheaths surrounding axons, and electrogenetically active axolemmal foci have evolved independently in widely different phyla. In addition to endowing the axons to conduct trains of impulses at a high speed, myelination and node formation results in a remarkable saving of space and energy. This is particularly important in the CNS, where space is restricted. Unlike the PNS, most CNS axons are myelinated, and several axons may be myelinated by a single cell. This adds further economy of space and energy. On the other hand the high level of complexity of the CNS white matter makes it vulnerable. There are several different kinds of disease affecting myelinated fibre tracts, particularly with respect to CNS white matter. (2) The CNS node of Ranvier presents a more complex structure the larger the fibre. The constricted nodal axon is encircled by perinodal astrocytic processes which contain large gliosomes and emit delicate processes towards the nodal axolemma. One astrocyte may project to several nodes. The node gap contains a polyanionic extracellular material. (3) Lamellated myelinoid bodies are frequent along paranodes of large myelinated CNS fibres. These bodies probably form through budding off from the paranodal myelin sheath. Similar bodies are seen inside astrocytes and microglia. The observation that these bodies are Marchi-positive and argyrophilic, and the presence of acid phosphatase activity around myelinoid bodies inside microglia suggests that they might represent degenerating myelin quanta, involved in the turnover of large myelin sheaths. This putative quantal release and breakdown of myelin material must be compensated for by a production of new myelin at other sites. Therefore, myelination may be viewed as a process that continues throughout life. (4) Biochemical analysis of a sub-cellular fraction enriched in myelinoid bodies shows that these bodies have a composition basically similar to that of myelin. However, breakdown products of myelin constituents, as well as exotic high molecular substances, not present in conventional myelin, can also be found. In addition, the myelinoid body fraction contains proteolytic activity. Studies using isotope labelling of myelin proteins show a source-product relation between myelin and myelinoid bodies. Altogether these data strongly support the hypothesis that myelinoid bodies reflect the catabolic side of myelin turnover. (5) Axons in the nerve fibre layer of the adult rat retina are all unmyelinated, although their diameters range up to over 2 microns. These axons exhibit focally differentiated axolemmal areas. At these sites the axolemma presents a dense undercoating with externally associated Müller cell processes or astrocytic processes.(ABSTRACT TRUNCATED AT 400 WORDS)

Teeth and tooth nerves

(1) Although our knowledge on teeth and tooth nerves has increased substantially during the past 25 years, several important issues remain to be fully elucidated. As a result of the work now going on at many laboratories over the world, we can expect exciting new findings and major break-throughs in these and other areas in a near future. (2) Dentin-like and enamel-like hard tissues evolved as components of the exoskeletal bony armor of early vertebrates, 500 million years ago, long before the first appearance of teeth. It is possible that teeth developed from tubercles (odontodes) in the bony armor. The presence of a canal system in the bony plates, of tubular dentin, of external pores in the enamel layer and of a link to the lateral line system promoted hypotheses that the bony plates and tooth precursors may have had a sensory function. The evolution of an efficient brain, of a head with paired sense organs and of toothed jaws concurred with a shift from a sessile filter-feeding life to active prey hunting. (3) The wide spectrum of feeding behaviors exhibited by modern vertebrates is reflected by a variety of dentition types. While the teeth are continuously renewed in toothed non-mammalian vertebrates, tooth turnover is highly restricted in mammals. As a rule, one set of primary teeth is replaced by one set of permanent teeth. Since teeth are richly innervated, the turnover necessitates a local neural plasticity. Another factor calling for a local plasticity is the relatively frequent occurrence of age-related and pathological dental changes. (4) Tooth development is initiated through interactions between the oral epithelium and underlying neural crest-derived mesenchymal cells. The interactions are mediated by cell surface molecules, extracellular matrix molecules and soluble molecules. The possibility that the initiating events might involve a neural component has been much discussed. With respect to mammals, the experimental evidence available does not support this hypothesis. In the teleost Tilapia mariae, on the other hand, tooth germ formation is interrupted, and tooth turnover ceases after local denervation. (5) Prospective dental nerves enter the jaws well before onset of tooth development. When a dental lamina has formed, a plexus of nerve branches is seen in the subepithelial mesenchyme. Shortly thereafter, specific branches to individual tooth primordia can be distinguished. In bud stage tooth germs, axon terminals surround the condensed mesenchyme and in cap stage primordia axons grow into the dental follicle.(ABSTRACT TRUNCATED AT 400 WORDS)

Relation between myelin sheath thickness and axon size in spinal cord white matter of some vertebrate species

The relation between number of myelin lamellae and axon size in the CNS was examined by electron microscopy of spinal cord white matter fibres in different vertebrate species (cat, rabbit, guinea pig, rat, mouse, frog and perch). The results show that the number of myelin lamellae increases with increasing axon size in a non-linear fashion. Below an axon size of 4--5 micron the relation follows a fairly straight line but above this size rectilinearity is lost. The mouse and the frog differ from the pattern shared by the other animals. In the mouse the lamellar number increases more slowly with axon size and the relation is close to linear. In the frog the number of lamellae increases very slowly with axon size and the relation is markedly curvilinear. Measurements of the myelin repeating period show that in the mammals and the frog the average period of thick sheaths is about 85% of that in thin sheaths, in accordance with previous findings in the cat. In the perch a clearcut difference in this respect between thick and thin sheaths is not found. Calculations of the g-ratio on the basis of the findings indicate that it increases with increasing fibre size. This is most pronounced in the perch and the frog in which the g-ratio for the largest fibres far exceeds the functionally optimal value defined in theoretical analyses on impulse propagation.

Effects of sciatic nerve resection on L7 spinal roots and dorsal root ganglia in adult cats

The size, distribution, and number of nerve fibers and neuronal perikarya in the L7 spinal roots and ganglia of adult cats were examined 35, 90, and 190 days after ipsilateral sciatic nerve resection. With increasing survival time the size spectra of myelinated ventral root nerve fibers showed a progressive flattening of the alpha peak. In the dorsal roots the myelinated fiber size distribution exhibited a marked shift toward smaller sizes. The reduction in the proportion of large myelinated axons was particularly evident in the dorsal roots. Less clearcut changes were found in the size distribution of spinal ganglion neuronal perikarya. No significant loss of axons could be detected in ventral or dorsal roots. There was, however, a marked reduction in the number of dorsal root ganglion neurons. This discrepancy suggested the possibility that an initial loss of dorsal root axons was concealed by recurrent sprouting of axons from the proximal nerve stump. However, neuroma excision 90 days after nerve resection did not lead to any reduction in dorsal root axon numbers. Thus, any ingrowth of new axons to the dorsal root should occur from levels proximal to the neuroma. In comparison with previous findings in kittens, peripheral nerve resection in adult cats had significantly smaller effects on sizes and numbers of spinal root nerve fibers as well as of dorsal root ganglion neurons. Therefore, the potential for restitution of the peripheral innervation by axon regeneration appeared to be basically greater in mature than in immature animals.

Axo-glial relations in the retina-optic nerve junction of the adult rat: electron-microscopic observations

SummaryThe retina-optic nerve junction (ROJ) was examined by electron microscopy in adult rats, with particular emphasis on the unmyelinated-myelinated nerve fibre transition. Both single sections and serial sections were used. The non-retinal part of the ROJ is covered by an extensively folded glia limitans, facing the choroidea, sciera and pia mater. The blood vessels within the ROJ follow a transverse course and are surrounded by unusually wide perivascular spaces with a glia limitans-like outer delimitation. The endothelial cells exhibit numerous pinocytotic vesicles on their abluminal aspect. In the unmyelinated part of the ROJ the axons are embedded in an extensive meshwork of fibrous astrocytic processes. Some unmyelinated axons exhibit patches of axolemmal undercoating with externally associated astrocytic processes. Typical oligodendrocytes are not found, but a few small dark glial cells of unknown identity can be observed. Atypical ensheathment and myelination of axons at this level by ectopic Schwann cells occurred in one case. In the transition segment of the ROJ a pattern similar to that along dysmyelinated axons is observed, including aberrant axo-glial contacts, unusually thin and short myelin sheaths, intercalated unmyelinated segments, distorted myelin termination regions, bizarre paranodes and myelin termination regions without associated nodally differentiated axolemma. Neither sheath length nor number of myelin lamellae is related to axon diameter in the transition region. Axon diameter tends to be somewhat larger at myelinated than unmyelinated levels of the same axon. We suggest that the unusual axo-glial relations in this region are due to a deficient proliferation and differentiation of oligodendroglial cells, and that the pattern of glial ensheathment in the ROJ might be a consequence of the locally deficient blood-brain barrier.

Changing relation between onset of myelination and axon diameter range in developing feline white matter.

The size spectra of unmyelinated, ensheathed and initially myelinating CNS axons were examined by electron microscopy in the spinal cord ventral funiculus and the corpus callosum of the cat during development. The first myelin sheaths appeared 4 weeks before and 3 weeks after birth in the spinal and callosal areas, respectively. De novo myelination had largely ceased by 4 months in the ventral funiculus and by 7 months in the corpus callosum. The result show that the diameter ranges, within which spinal and callosal axons undergo primary ensheathment and initial myelination, are markedly different if similar levels of myelination are compared. In both areas, these diameter ranges shift towards smaller sizes with development. However, spinal and callosal axons, which undergo primary ensheathment and initial myelination simultaneously, present comparable diameter ranges. The findings support the view that other factors than the absolute physical size of the axon trigger initiation of CNS myelination. In this respect the developmental stage of the animal appears to play an important role.

Effects of sciatic nerve crush on the L7 spinal roots and dorsal root ganglia in kittens

The number and size distribution of axons and neurons were examined in the L7 spinal roots and ganglia of kittens 14 to 220 days after early postnatal sciatic nerve crush. The results show that motoraxons in the ventral root as well as axons and perikarya of sensory neurons in the dorsal root remained growth-retarded throughout the examined period. This was most evident in the dorsal root. Both ventral and dorsal roots showed some loss of myelinated axons, but this was only half that previously observed after sciatic nerve resection. Whereas in the dorsal roots and dorsal root ganglia the loss seemed to be nonselective with respect to size, axons in the gamma range were primarily affected in the ventral roots. In the dorsal roots the proportion of unmyelinated axons was comparable with controls but in the ventral roots it was somewhat elevated. In most cases the loss of dorsal root ganglion neurons was relatively greater than the decrease of dorsal root axons.

Occurrence of unmyelinated axon profiles at distal, middle and proximal levels in the ventral root L7 of cats and kittens

The proportion of unmyelinated axon profiles (UAP) was estimated electronmicroscopically at different proximo-distal levels in the ventral root L7 of 7 normal adult cats and 2 kittens. In 3 of the adult cats the occurrence of UAP was also determined in the juxtamedullary root fascicles, including the CNS/PNS transitional region. Three additional adult (male) cats, which had been subjected to prepubertal castration, were examined at mid-root level. Prepubertal castration was found not to interfere with the increase in L7 ventral root UAP that takes place during puberty. In the normal animals the proportion of UAP was highest distally in the ventral root and decreased as the spinal cord was approached. The same trend was seen in cats and kittens, but the values were obviously higher in adults. The content of UAP decreased markedly in the immediate vicinity of the CNS/PNS border. Very few unmyelinated axons and no myelinated CNS-type axons with sizes below the gamma range were found on the CNS side of this border. In addition groups of PNS-type unmyelinated and small myelinated axons occurred in the pia mater outside some juxtamedullary root fascicles.

Structural changes in kittens' ventral and dorsal roots L7 after early postnatal sciatic nerve transection

Abstract The number and size distribution of myelinated and unmyelinated axons were studied in spinal roots L7 of 19 kittens, 8 to 200 days after early postnatal left sciatic nerve transection. Ventral and dorsal roots on the side of transection were compared with corresponding contralateral roots. Three normal kittens were used as additional controls. On the control side the proportion of unmyelinated ventral root axons increased from about 15 to 30% between 3 and 7 months postnatally. In the ventral roots on the lesion side there was a loss of myelinated axons of all sizes (total loss 15 to 25%). The loss seemed to be somewhat greater in the gamma population. The number of unmyelinated ventral root axons increased markedly through sprouting. This increase was similar at different root levels. The persistence of such axonal sprouts in the proximal stump after ventral root division in one kitten indicated that they originate proximally in the ventral root or within the central nervous system. The dorsal roots on the lesion side showed a 30% deficit of both myelinated and unmyelinated axons. Signs of axonal sprouting were not observed. Both in ventral and dorsal roots the size spectra of myelinated axons were markedly shifted to the left on the lesion side due to a growth retardation of larger axons. With respect to the unmyelinated axons the size distribution was expanded toward larger sizes in the ventral roots and remained largely unaltered in the dorsal roots.

Myelin sheath thickness and internodal length of nerve fibres in the developing feline inferior alveolar nerve

The relation between the number of myelin lamellae (nl) and axon size (d) was examined in the developing and adult feline inferior alveolar nerve (IAN). The internodal lengths (L) and total diameters (D) were measured on teased IAN specimens from kittens and cats. The results show that relations nl/d and L/D principally similar to those in young adult cats had been established 2 months after birth. This coincides with the maturation of the primary dentition. During the first 3 postnatal weeks signs of a developmental demyelination were common. Comparisons between the internodal elongation of early myelinating axons and the longitudinal growth of the IAN in the mandibular canal indicated that some 50% of all prospective large internodes must be removed. Between 2 months and the young adult stage, when the permanent dentition is established, the relations nl/d and L/D were essentially unaltered, but the ranges extended towards larger sizes. In the young adult the average g-value was 0.67. In the old adult cat the relation nl/d was less uniform than in young adults, and the average g-value had decreased to 0.59. In addition, successive short (100-150 micrometer) internodes were found, indicating a senescent de- and remyelination in the IAN. These alterations may be related to the age-dependent deterioration of the mandibular dentition.