Biomedical subjects

C Hildebrand

Publications and source records attributed to C Hildebrand.

At least 109 records · Page 6Linked to original sources

PubMed1984

Postnatal differentiation of rat optic nerve fibers: electron microscopic observations on the development of nodes of Ranvier and axoglial relations.

The postnatal differentiation of rat optic nerve fibres was examined by transmission electron microscopy. The results show that many early developing axons contain clusters of vesiculotubular profiles prior to myelination. At places vesicular elements appear to fuse with the axolemma, and, in addition, some axons exhibit deep axolemmal invaginations and axoplasmic lamellated bodies. It is suggested that these features might reflect axolemmal remodelling, possibly involving axoglial signalling and/or functional differentiation of the axolemma. The size distribution of unmyelinated optic nerve axons changes little during development. Ensheathment of larger axons commences 6 days postnatally. The subsequent formation of compact myelin sheaths is accompanied by an increase in axonal diameter. The early sheaths are a few microns long and separated by long bare axon segments. In optic nerves from 10-12-day-old rat pups, a few sheaths consisting of about five layers border primitive asymmetric nodes with a patchy axolemmal undercoating. Extensions from one of the terminating sheaths are often associated with undercoated patches of axolemma. Relatively differentiated nodes of Ranvier first appear 14-16 days after birth. The continued nodal maturation involves establishment of a regular nodal geometry, increasing distinctness of the axolemmal undercoating, and formation of perinodal astrocytic processes embedded in an extracellular node gap substance. The results are compared with available data on the conduction properties of rat optic nerve fibres during development.

Animals↗

PubMed1984

Membrane specialization and axo-glial association in the rat retinal nerve fibre layer: freeze-fracture observations.

The ultrastructure of non-myelinated ganglion cell axolemma within the retinal nerve fibre layer of adult rats was examined by thin section and freeze-fracture electron microscopy. Most of the axolemma within the nerve fibre layer does not exhibit any membrane specializations; intramembranous particles are partitioned with a density of approximately 1750 microns-2 on the P-fracture face and approximately 225 microns-2 on the E-face of the non-specialized axolemma. The nerve fibres also exhibit specialized foci of axolemma, at which the axons are abutted by the tips of blunt, radially oriented processes from Müller cells. At such sites of axo-glial association, an electron-dense undercoating is present beneath the axon membrane. Freeze-fracture analysis revealed a substantial increase in the density of E-face particles (greater than 500 microns-2) at sites of association between the tips of blunt glial processes and the axon. These findings demonstrate that non-myelinated axolemma of the retinal nerve fibre layer can exhibit spatial heterogeneity, with patches of node-like membrane at regions of specialized association with glial cell processes. On the basis of their morphological similarity to nodes of Ranvier, we suggest that these specialized axon regions represent foci of inward ionic current.

Animals↗

PubMed1984

Invasion of the L7 ventral root and spinal pia mater by new axons after sciatic nerve division in kittens.

In young kittens the left sciatic nerve was divided followed by nerve suture, distal stump resection, or resection combined with proximal stump capping. The kittens were killed 2 to 3 months postoperatively. In other kittens bilateral L7 ventral rhizotomy or neuroma excision was carried out 80 to 90 days after nerve resection, followed by killing a few days later. Thin sections from the ventral root L7 were examined in the electron microscope. In all animals the average proportion of ventral root unmyelinated axon profiles (UAP) was above normal on the operated side, being highest in capped and resected animals and lower in sutured cases. The proportion of UAP was inversely related to the extent of functional calf muscle reinnervation. In cases with high proportions of UAP, numerous bundles of unmyelinated and small myelinated axons were present in juxtamedullary root fascicles and surrounding pia mater. After L7 ventral rhizotomy in resected animals few intact UAP occurred together with numerous signs of axon degeneration in the proximal root stump on the lesion side. After neuroma excision the proportion of ventral root UAP decreased. Therefore some proportion of the new axons should represent recurrent sprouts from peripheral sources.

Animals↗

PubMed1983

Reinnervation of the ventral root L7 from ventral horn neurons following intramedullary axotomy in adult cats.

Through small longitudinal incisions in the ventral funiculus of the adult cat spinal cord the intramedullary portions of motoraxons forming the L7 ventral root were divided. The animals were sacrificed by glutaraldehyde-perfusion 1-15 weeks postoperatively. In some cases this was preceded by HRP injection into large L7 ventral horn neurons. Sections from the lesioned ventral funiculus and the denervated ventral root L7 were examined by light and electron microscopy. During the first postoperative month increasing numbers of unmyelinated and thinly myelinated large-diameter axons coursed through the lesion and entered the denervated ventral root. Occasional neuroma-like formations were also found in the lesion area. After 5 weeks survival clusters of regenerating axons reached the distal end of the L7 ventral root. Light microscopic examination of Vibratome sections from HRP-injected animals showed that at least some regenerated axons come from large neurons, presumably alpha-motoneurons, in the ventral horn motor nuclei. Most of the examined labeled regenerated axons reached the CNS/PNS junction of the ventral root but a few followed a grossly aberrant course and/or terminated within the lesion. These observations show that regeneration of large-diameter axons through a CNS-lesion is possible. Both the intrinsic regenerative capacity of the axotomized neurons and the presence of a denervated ventral root in the immediate vicinity are likely to be contributing factors with respect to this example of successful CNS axon regeneration.

Animals↗

PubMed1983

Proportion of unmyelinated axons in the rat inferior alveolar nerve and mandibular molar pulps after neonatal administration of capsaicin.

Neonatal rats were given capsaicin subcutaneously. Controls received vehicle only. Six months later the nerve fiber populations in the dorsal root L4, in the inferior alveolar nerve and in mandibular molar pulps were examined by electron microscopy. The proportion of unmyelinated axons was found to be markedly decreased in root and nerve specimens from capsaicin-treated rats. However, the pulpal nerves in tooth specimens from these rats showed no obvious alterations.

Animals↗

PubMed1983

Sural nerve biopsies from workers with a history of chronic exposure to organic solvents and from normal control cases. Morphometric and ultrastructural studies.

An ultrastructural and morphometric study was performed on sural nerve biopsies of four industrial spray painters (35-59 years) and 11 controls (6-64 years). No difference could be shown in spray painters and age-matched controls as to the number of myelinated nerve fibres per area, their size distribution, variation of internodal length along single nerve fibres or the ratio between the number of myelin lamellae and the axon circumference. There was marked scattering of the two latter parameters in older exposed and and control individuals. The distribution of NADH2-tetrazolium reductase activity was similar in exposed and control cases. The general ultrastructural appearance of nodal-paranodal regions in controls conformed with that noted in experimental animals. The overall ultrastructural organization and age-related changes of nerves of exposed cases were similar to those of control cases except for a presence of paranodal axonal mitochondria which contained glycogen-like particles in exposed cases. In one exposed case abundant dispersed or clustered glycogen-like particles were seen in the paranodal axoplasm. These findings are suggested to be an effect of chronic exposure to organic solvent vapours. Ageing seems, however, to have a much greater impact on the morphology of the sural nerve fibre than occupational exposure to organic solvent.

Adult↗

PubMed1983

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.

Animals↗

PubMed1983

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.

Animals↗

PubMed1982

Regenerating mammalian nerve fibres: changes in action potential waveform and firing characteristics following blockage of potassium conductance.

Extracellular application of potassium channel blocking agents is known to increase the amplitude and duration of the compound action potential in non-myelinated and demyelinated axons, but not in mature mammalian myelinated fibres. In the present study we used intra-axonal and whole nerve recording techniques to study the effects of the potassium channel blocking agent 4-aminopyridine (4-AP) on regenerating rat nerve fibres. Our results indicate that early regenerating (premyelinated) axons show considerable broadening of the action potential after 4-AP application and late regenerating (myelinated) axons give rise to burst activity following a single stimulus after 4-AP application. 4-AP did not affect spike waveform or firing properties of normal mature sciatic nerve fibres. These results demonstrate the importance of potassium conductance in stabilizing firing properties of myelinated regenerating axons.

Action Potentials↗

PubMed1982

Electron-microscopic identification of Gomori-positive rings in normal spinal cord white matter.

Longitudinal vibratome slices from glutaraldehyde-fixed adult guinea pig lateral funiculus white matter were incubated in a Gomori medium, stained with ammonium sulfide, osmicated and section-embedded in vestopal. Following light-microscopic localization of ring-shaped deposits of reaction product series of thin sections were cut from these areas. In the electron microscope ring-shaped deposits of reaction product were consistently found to surround lamellated myelinoid bodies within glial cells. By following the series some of these cells could be identified as microglia. Sparse aggregates of reaction product were occasionally seen outside myelinoid bodies in typical astrocytes. Precipitates were not related to myelinoid bodies associated with typical oligodendrocytes. The findings suggest that microglia and possibly astroglia participate in the breakdown of spontaneously formed myelin fragments in normal adult white matter.

Animals↗

PubMed1982

Axon number and size distribution in the developing feline inferior alveolar nerve.

The number and size distribution of axons in the developing feline inferior alveolar nerve (IAN) were examined by electron microscopy. Seven cat fetuses and thirty kittens and cats aged from 25 days post conception (dpc) to 11 years were used. The total number of IAN axons increased from 4,400 to 16-17,000 between 25 and 40 dpc, and then decreased to about 13,000 before birth. This level was maintained up to at least 11 years. Myelinated axons first appeared by 45 dpc and constituted 28% at birth. The young adult proportion of about 45% myelinated axons was established at 2 months. In the old adult (11 years) 55% of the IAN axons were myelinated. Size measurements showed that unmyelinated axons had diameters of 0.1-0.5 micrometer at 25 dpc. From 55 dpc and on the size range extended from 0.1 micrometer to 1 micrometer. The size range of myelinated axons was 1-4.5 micrometers at birth and 1-8 micrometers 2 months postnatally. A bimodal size distribution first appeared by 2 months, and the range was 1-13 micrometers from 6 months and on. The findings were compared with age-related changes in the primary and permanent dentitions.

Aging↗

PubMed1982

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.

Aging↗

PubMed1982

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.

Animals↗

PubMed1982

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.

Animals↗

PubMed1982

Qualitative structural development of the feline inferior alveolar nerve.

The qualitative structural development of the inferior alveolar nerve was studied by electron microscopy in 56 pre- and postnatal kittens and 21 young and old adult cats. At 25 days post conception the nerve was composed of a bundle of small axons enclosed by primitive sheath cells. Three weeks later myelination had been initiated. Axons measuring 2-3 micrometers underwent local demyelination from 2 weeks before to 3 weeks after birth. This was accompanied and followed by nodalization of larger axons. A typical perineurium was first apparent in the newborn kitten. Six to eight weeks postnatally, the nerve appeared qualitatively mature, although axonal growth was far from completed. This coincides with achievement of a fully mature primary dentition shortly after the weanling period. Apart from a continued size growth, no changes were observed in the nerve during the transition from the primary to the permanent dentition. In the inferior alveolar nerve of old cats, axonal and perineurial changes co-existed with signs of dental attrition and pathology.

Alveolar Process↗

PubMed1981

Pulpal axons in developing, mature, and aging feline permanent incisors. A study by electron microscopy.

The ingrowth, maturation, and aging of pulpal axons was followed by electron microscopy in permanent mandibular incisors of 44 cats aged 35 days-11 years. The first axons entered the incisor pulps about 2 months after birth. Cells resembling Schwann cells, but lacking an axonal relation, were also observed at this time. Axonal ingrowth and maturation continued until 7 months, when the pulps contained 92-394 axons, 81-88% of which were unmyelinated. Between month 7 and 20 months the character of the incisor pulpal axons remained largely unchanged. In adult cats the myelinated pulpal axons had diameters of 1-6 micrometer. The relation between the number of myelin lamellae and the axon size correlated better with linear + logarithmic than linear functions. The g-ratios were higher than in most peripheral nerves, and tended to increase with axon diameter. In the old adult this tendency was more evident and the g-ratios were generally lower. From 3 years on the incisors displayed various age-related or pathological alterations. These were accompanied by axonal changes and axon loss. In contrast to earlier stages perineuriumlike sheaths were frequent in old teeth. The findings are discussed in relation to axon development in the inferior alveolar nerve and in primary incisor pulps.

Aging↗

PubMed1981

Developmental growth and degeneration of pulpal axons in feline primary incisors.

The life history of pulpal axons in primary mandibular incisors was examined by light and electron microscopy in 56 kittens aged from 25 days postconception to 120 days after birth. Cells resembling Schwann cells preceded the first arrival of pulpal axons, 1 week postnatally. myelination was initiated during the second week. Two months after birth the incisors were fully grown and each pulp contained about 100 axons. Between 10 and 20% of these were myelinated and ranged in size from 1 to 5 micrometer. The relation between number of myelin lamellae and axon size appeared nonlinear and differed markedly from that in similarly sized inferior alveolar nerve axons. During the third month many unmyelinated axons showed signs of degeneration. With progress of root resorption an increasing proportion of both unmyelinated and myelinated axons degenerated. In highly resorbed incisors necrotic Schwann cells were associated with degenerating axons and there was a generalized pulpal tissue reaction. In some teeth with advanced root resorption pulpal axons were lacking. A progressive derangement of all pulpal tissue elements continued until shedding during the second half of the fourth month. In incisor nerve branches below the incisor teeth axon degeneration was very limited.

Aging↗

PubMed1981

Postnatal increase of unmyelinated axon profiles in the feline ventral root L7.

The proportion of unmyelinated axon profiles and possible age-related, degenerative and regenerative alterations were studied ultrastructurally in the L7 ventral root of 25 cats ranging form 3 weeks to 11 years of age. For comparison, the ventral root C6 was examined in 5 of these animals. The sections were taken from a level midway between the proximal and distal ends of the roots. The proportion of unmyelinated axon profiles in the L7 ventral root increased from about 14% to around 31% between 4 and 7 months after birth. Simultaneously, the average number of unmyelinated axon profiles per Schwann cell was doubled from 2-3 to 4-5. Thereafter, these figures remained largely unchanged for at least a decade. The total number of myelinated axons was similar in kittens and in cats. In the C6 root the proportion of unmyelinated axon profiles was about 20%, both in kittens and in young or old adult cats. At both segmental levels in the oldest cats, some unmyelinated axons showed degenerative changes and medium-sized and large axons had features characteristic of demyelination and remyelination.

Aging↗