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J P Fraher

Publications and source records attributed to J P Fraher.

At least 19 recordsLinked to original sources
PubMed1997

Axon-glial relationships in early CNS-PNS transitional zone development: an ultrastructural study.

The CNS-PNS transitional zone of rat cervical ventral rootlets develops in two stages: first, axon segregation, then transitional node formation. This ultrastructural study examines the former. Material was prepared by standard methods. Shortly after they grow out from the neural tube, ventral motoneuron axon bundles are extensively segregated by a matrix of fine processes forming a barrier across the rootlet, just distal to the cord surface. These processes arise from cell clusters on the rootlet surface. This barrier is prominent until the period around birth, when it is replaced by a second in which the axons are completely segregated from one another. The perikarya and processes forming this barrier resemble those of the first, but lie at or just below the cord surface. Thus, beginning at the earliest stage, a barrier crosses the axon bundle and segregates its axons before axon segregation is advanced either in the PNS or (especially) in the CNS. This may prevent central Schwann cell migration. Evidence is presented suggesting that the second barrier may arise through a relative proximal relocation of the first, as the cord grows radially. Near the cord surface, a complete, funnel-shaped sleeve of glial processes surrounds the axon bundle. This is continuous at the cord surface with the glia limitans. It constitutes an integral part of the transitional zone apparatus. It is also continuous centrally with the sheath which enfolds the bundle of ventral motoneuron axons as they run between the ventral horn and the transitional zone. Axon segregation at the cord surface, and therefore the formation of the definitive astrocytic CNS-PNS barrier occur relatively (and perhaps surprisingly) late at the cord surface. The definitive sharp discontinuity of central and peripheral tissue types characteristic of the transitional zone is established only after birth.

Aging↗
PubMed1994

Morphological specialisations of rat cranial nerve transitional zones.

Near their CNS-PNS transitional zones (TZs), many rat cranial nerve rootlets are subdivided to a marked degree by a reticulum of fine cytoplasmic processes. Some of the resulting compartments contain only a single myelinated fibre or a bundle of collagen fibrils. The compartments are aligned with the astrocytic tunnels in which the fibres lie as they traverse the CNS-PNS transitional zone. This marked subdivision may help to insulate individual fibres from one another, preventing functional interaction between them. Rootlet sheath cells commonly are closely apposed to, or interdigitate with, astrocyte processes of the TZ. These features may help to strengthen the delicate TZ. The TZ of the trochlear nerve includes a long, generally avascular, central tissue projection (CTP) into the proximal part of the nerve. This is connected to the brainstem and cerebellum by astrocytic bridges. In contrast to the CTP, which is generally avascular, these contain abundant blood vessels which may facilitate metabolic exchange in the trochlear TZ.

Animals↗
PubMed1993

Spacing of central-peripheral transitional nodes of rat motoneurones.

Node of Ranvier distribution is examined in the two basic types of CNS-PNS transitional zone (TZ) related to rat spinal nerves. Type 1 TZ is short and lies at the cord surface. Type 2 is long and lies in the proximal part of the rootlet. Nearest neighbour distance measures the length between adjacent node centres and is a better estimate of node spacing than simple density measurements. Many nearest neighbour distances measure less than 10 microns. The nearest neighbour distance means (ca. 13.5 microns) and distributions are similar in both TZ types, suggesting that developmental influences on node separation are also similar in both locations. Fibres traversing the TZ are separated by large amounts of astrocytic tissue. This may prevent functional interaction between their closely packed nodes.

Animals↗
PubMed1992

Myelin-axon relationships in the rat phrenic nerve: longitudinal variation and lateral asymmetry.

It is known that the myelin sheath thickness-axon perimeter relationship varies between peripheral nerves. This study examines the possibility that that relationship may vary between levels along a given nerve or between corresponding levels of the right and left examples of the same nerve. The relationship is examined for large and small fibre classes at well separated upper and lower intrathoracic levels in the rat phrenic nerve. The study shows that the myelin-axon relationship differs between levels along the same nerve bundle in the same (intrathoracic) environment. Thus, for a given increase in the perimeter of large axons, sheath thickness increases significantly more at lower than at upper levels. In addition, myelin sheath thickness shows a statistically significant lateral asymmetry in favour of the left side for the large fibre class at the upper thoracic level. The setting of the myelin sheath thickness-axon perimeter relationship also differs between the large and small fibre classes at each level examined. Large fibres have proportionately thicker sheaths than small fibres and this difference is reflected in the significantly smaller g-ratio of the former. Systematic differences in the setting of the myelin sheath thickness-axon perimeter relationship between large and small fibre classes may be a widely occurring phenomenon. It may be concluded that the myelin-axon relationship varies significantly both within and between nerves and also between fibre classes. Accordingly, morphometric studies of normal or pathological nerves should take into account possible consistent longitudinal variation or lateral asymmetry in fibre parameters and myelin-axon relationships within a given nerve bundle or fibre class, in order to avoid introducing systematic bias and to minimize variance between samples.

Animals↗
PubMed1992

The CNS-PNS transitional zone of the rat. Morphometric studies at cranial and spinal levels.

The transitional zone is that length of rootlet containing both central and peripheral nervous tissue. The CNS-PNS interface may be defined as the basal lamina covering the intricately interwoven layer of astrocyte processes which forms the CNS surface and which is pierced by axons passing between the CNS and PNS. Study of transitional zone development defines morphologically the growth, relative movement and interaction of central and peripheral nervous tissues as they establish their mutually exclusive territories on either side of the CNS-PNS boundary, and helps to explain the wide variations in the form of the mature transitional zone. Nerve rootlets at first consist of bundles of bare axons. These become segregated by matrices of fine Schwann cell processes peripherally and of astrocyte processes centrally. The latter may prevent Schwann cell invasion of the CNS. Astrocyte processes branch profusely and come to form the principal central nervous tissue component of the transitional zone. Developmental changes in the transitional zone vary markedly between nerves, reflecting differences in its final morphology. Widespread relative movements and migration of CNS and PNS tissues take place during development, so that the central-peripheral interface changes shape and position, commonly oscillating along the proximodistal axis of the rootlet. For example, developing cervical ventral rootlets contain a transient central tissue projection, while that of lumbar ventral rootlets and to a lesser extent that of cervical dorsal rootlets alternately increase and decrease in length. In the developing cochlear nerve, a central tissue projection is present before birth, but regresses somewhat before a marked outgrowth of central nervous tissue along the nerve takes place, which reaches into the modiolus during the first week postnatum. During development, some astrocytic tissue may even break off and migrate distally into the root, giving rise to one or more glial islands within it. During the period immediately preceding birth, Schwann cells come to be present in very large numbers in that part of the rootlet immediately distal to the CNS-PNS interface, the proximal rootlet segment. Here they form prominent sleeves or clusters of closely packed cells which intertwine with and encapsulate one another on the rootlet surface. Such Schwann cell overcrowding in the proximal rootlet segment could result in part from distal overgrowth of the rapidly expanding CNS around axon bundles, which might strip the Schwann cells distally off the bundle segments so engulfed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Incidence of sarcocysts in skeletal muscles of horses.

The incidence of sarcocysts was examined in postural, propulsive and respiratory muscles from 74 horses ranging in age from mid-gestation to 14 years post-natal. Cryostat sections were stained for myosin adenosine triphosphatase (ATPase) at pH 9.5 and the type of muscle fibre containing sarcocysts was identified. Sarcocysts were found in muscles from three animals, all aged 1 year or more. Counts showed that they displayed no preference for any particular muscle. However, fibres with a high activity for myosin ATPase were preferentially colonized. Transverse sectional profiles of sarcocysts showed a wide variation in size, shape and wall thickness. Both the proportion of horses infected and the intensity of infection per animal were considerably lower than those reported in other studies.

Animals↗
PubMed1992

Experimental traction injuries of cervical spinal nerve roots: a scanning EM study of rupture patterns in fresh tissue.

This study examines the levels at which fresh rat ventral and dorsal C4 to T1 spinal roots rupture under traction stress. Rupture rarely occurs at the CNS-PNS transitional zone. Despite its delicate appearance this is strengthened in a number of ways, so that it is less vulnerable than the roots and their constituent rootlets and aggregated rootlet bundles (ARBs). Ventral roots commonly rupture either where the rootlets join to form the ARBs, along the course of the latter, or where these in turn join to form the ventral root. Dorsal root rupture shows a similar pattern but has a higher frequency of rupture within the root proper than is the case with the ventral roots. The level of rupture also varies systematically over the series of roots examined: rupture points tend to be located at more distal levels in caudal roots. This may occur because of mechanical differences in the distribution of traction stress along roots, related to their courses through the vertebral canal. Upper roots run transversely and the traction force is transmitted directly to rootlet levels, while more caudal roots run obliquely and tend to rupture where they are drawn taut against the pedicle. Many of the morphological features of ruptured roots would tend to inhibit regeneration of fibres distally. Differences in the pattern of rupture between fresh and fixed roots are examined. The latter tend to rupture at levels closer to the CNS than the former.

Animals↗
PubMed1991

Myelin-axon relationships established by rat vagal Schwann cells deep to the brainstem surface.

The central-peripheral transitional zones of rat dorsolateral vagal rootlets are highly complex. Peripheral nervous tissue extends centrally for up to several hundred micrometers deep to the brainstem surface along these rootlets. In some instances this peripheral nervous tissue lacks continuity with the peripheral nervous system (PNS) and so forms an island within the central nervous system (CNS). In conformity with the resulting complexity of the CNS-PNS interface, segments of vagal axons lying deep to the brainstem surface are myelinated by one or more intercalated Schwann cells, contained in peripheral tissue insertions or islands, at either end of which they traverse an astroglial barrier. Intercalated Schwann cells are thus isolated from contact or contiguity with the Schwann cells of the PNS generally. They are short, having a mean internodal length of around 60% of that of the most proximal Schwann cells of the PNS proper, which lie immediately distal to the CNS-PNS interface and which are termed transitional Schwann cells. The thickness of the myelin sheaths produced by intercalated Schwann cells is intermediate between that of transitional Schwann cells and that of oligodendrocytes myelinating vagal axons of the same calibre distribution. This is not due to limited blood supply or to insufficient numbers of intercalated Schwann cells, the density of which is greater than that of transitional Schwann cells. These factors are unlikely to restrict expression of their myelinogenic potential. Nevertheless, the regression data show that the setting of the myelin-axon relationship differs significantly between the two categories of Schwann cell. Thus, the myelinogenic response of Schwann cells to stimuli emanating from the same axons may differ between levels along one and the same nerve bundle. Mean myelin periodicity was found to differ between sheaths produced by intercalated and by transitional Schwann cells.

Animals↗
PubMed1991

Central-peripheral transitional zone of the spinal accessory nerve in the rat.

The spinal accessory nerve rootlets emerge from the lateral aspect of the upper five segments of the cervical spinal cord underlying the nerve trunk. They cross the lateral funiculus of the cord with a slight rostral inclination. Here some pursue a relatively straight course while others have a dorsal convexity. The transitional zones may be classified into three distinct types, related to their orientation as they traverse the glia limitans to emerge as free rootlets. The fibres in Type 1 rootlets bend sharply rostrally on reaching the glia limitans. Type 2 rootlets turn ventrally to run in the glia limitans in the transverse plane of the cord before emerging. Type 3 rootlets are found only at C1. Their fibres initially turn caudally in the glia limitans and then loop rostrally. The morphology of the central-peripheral transitional zones of the spinal accessory rootlets closely resembles that of cervical ventral rootlets, and is therefore correlated with the motor function of these rootlets rather than with their intermediate location between the ventral and dorsal cervical rootlets.

Accessory Nerve↗
PubMed1990

Relative growth and maturation of axon size and myelin thickness in the tibial nerve of the rat. 1. Normal animals.

Morphometric observations have been made on the medial plantar division of the tibial nerve (MPD) and on the motor branches of the tibial nerve to the calf muscles (MBC) in rats ranging in age from weaning (3 weeks) to 12 months. Axon size, assessed by measurements of circumference and cross-sectional area, increased rapidly until 3 months with further slight increases between 3 and 9 months and a slight fall between 9 and 12 months. Axon size distributions were unimodal throughout in the MPD but bimodal for the MBC except at 3 weeks. Distributions of myelin thickness were bimodal throughout for both nerves. Scatter plots of g ratios (axon diameter:total fibre diameter) confirmed the presence of two fibre populations: a group of small fibres with relatively thin myelin sheaths, and a group of larger fibres within which sheath thickness was relatively less on the larger than on the smaller axons. These two fibres populations were less easily separable in the MBC than in the MPD nerves. These results document morphometrically the normal growth changes in the rat tibial nerve and also provide control data for the analysis of the effects of experimental procedures on the growth and maturation of peripheral nerve fibres.

Aging↗
PubMed1990

Relative growth and maturation of axon size and myelin thickness in the tibial nerve of the rat. 2. Effect of streptozotocin-induced diabetes.

The relative changes in the growth and maturation of axon size and myelin thickness were studied in the medial plantar division of the tibial nerve in the lower leg and in the motor branches of the tibial nerve to the calf muscles in rats in which diabetes mellitus had been induced with streptozotocin at the time of weaning. Observations were made at 6 weeks and 3, 6, 9 and 12 months of diabetes for comparison with age-matched controls. Similar changes were observed in both nerves. Growth in body weight and skeletal growth was severely retarded from the time of induction of diabetes but at the 6-week stage axon size was not reduced, suggesting that neural growth may initially be relatively protected. At later stages axon size was consistently reduced in the diabetic animals as compared with the controls and showed an absolute reduction at 12 months, as compared with 9 months, that was greater than in the controls. Myelin thickness became reduced earlier and was more severely affected than axon size so that the fibers were relatively hypomyelinated. The myelin changes were greater in larger than in smaller fibers. The index of circularity of axons was reduced in the diabetic nerves. These results show that induction of diabetes in prepubertal rats produces effects on peripheral nerve fibers which differ from those resulting from diabetes induced in adult animals. The effects also differ between large and small nerve fibres. These observations may explain some of the disparate findings obtained in previous studies on experimental diabetes in rats.

Animals↗
PubMed1990

Intermingling of central and peripheral nervous tissues in rat dorsolateral vagal rootlet transitional zones.

The morphology of the CNS-PNS transitional zone of adult rat dorsolateral vagus nerve rootlets is uniquely complex. A typical rootlet contains a transitional zone over 300 microns long, consisting of a central tissue projection extending distally into each rootlet and a peripheral tissue insertion extending for a longer distance deep into the brainstem. The peripheral tissue insertion is continuous with the peripheral tissue of the free rootlet through channels traversing or running parallel to the central tissue projection. Accordingly, the vagal CNS-PNS interface is topologically much more complex than that found elsewhere. In some rootlets the peripheral tissue in the brainstem constitutes an isolated island deep within the neuraxis. In others, peripheral continuity is established only through a cross connection with the peripheral tissue insertion of a neighbouring rootlet. About one fifth of all vagal myelinated axons alternate between the CNS and PNS tissue compartments. This distinguishes the vagus from all other nerves studied to date. These axons are myelinated by Schwann cells distal to the transitional zone, by oligodendrocytes in the central tissue projection and by one or more short intercalated Schwann internodes further centrally, mostly in the peripheral tissue insertion, where their perikarya commonly form closely apposed aggregates. More than four fifths of all unmyelinated axon bundles alternate between central and peripheral tissue compartments, commonly more than once. In the peripheral tissue insertion axons are enveloped by series of non-myelinating Schwann cells. Schwann processes commonly extend for over 50 microns into the central compartment at each central-peripheral transition. Around one fifth of peripherally unmyelinated axons have an oligodendrocytic sheath in the central compartment. Of these axons possessing more than one intercalated Schwann internode, over one quarter display alternation of myelinated and unmyelinated segments in the peripheral tissue insertion. Astrocytes in the transitional zone segregate PNS tissue, a role played by sheath cells further peripherally in the vagal rootlets. Astrocytes form the surface limiting membranes of the central tissue projection and the barrier between the peripheral tissue insertion and the surrounding brainstem. The barrier consists only of an attenuated layer of processes. This is deficient in places, where oligodendrocytic myelin sheaths are directly exposed to the endoneurial space of the peripheral tissue insertion and in some instances are apposed to myelinating or non-myelinating Schwann cells. Such communication between the central and peripheral compartments is unique to the vagal transitional zone. The findings are consistent with a range of possible events during development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

High density of nodes of Ranvier in the CNS-PNS transitional zone.

Node of Ranvier density was examined at three levels along rat lumbar motoneuron axon bundles: where they lie in the central nervous system, in the peripheral nervous system and in the transitional zone (TZ) between these. Density was considerably and significantly greater in the TZ than in either of the other locations. It is possible that such densely packed nodes in the TZ could interact electrically with one another. Because of its structure and position and because it contains a relatively pure fibre population, the rat L4 ventral rootlet TZ lends itself readily to electrophysiological investigation of this possibility.

Animals↗
PubMed1989

Axon-myelin relationships in rat cranial nerves III, IV, and VI: a morphometric study of large- and small-fibre classes.

The primary objectives of this study were to determine (1) if quantitative axon-myelin relationships are similar for large- and for small-fibre classes within individual nerves and (2) if the same axon-myelin relationships hold for equivalent fibre classes in closely similar nerves. The oculomotor, trochlear, and abducent nerves of the rat were examined since they each contain distinct large- and small-fibre classes and are similar in a wide range of anatomical and developmental respects. Accordingly, morphometric analyses of axon-myelin relationships were performed separately on large and small fibres of each of the three nerves. Within each nerve, the setting of the relationship between the two parameters was found to be different for the two fibre classes: Scatterplots relating sheath thickness to axon perimeter for large fibres were shifted upwards relative to those for small fibres. These differences were also reflected in the positions of the regression lines fitted to the plots and in the g-ratios. Significant differences were found between nerves in relation to their large fibres: Those of the abducent nerve had significantly thicker sheaths, those of the oculomotor nerve had significantly smaller axon perimeters, and the myelin sheath-axon perimeter relationship of the abducent nerve differed significantly from that of the other two. This study therefore shows that morphometric axon-myelin relationships may differ significantly between equivalent fibre classes of nerves that are closely similar in respect of morphological class, central origin, peripheral distribution, developmental environment, and function.

Abducens Nerve↗
PubMed1989

Age changes in axon number along the cervical ventral spinal nerve roots in rats.

Axon counts were made at two standardised levels of C7 ventral spinal nerve roots from 46 female rats representing nine ages between birth and 500 days. The objective was to provide a definitive account of proximodistal changes in axon numbers and of age changes in axon numbers both during postnatal development and at several stages during maturity. At each age there is a proximodistal increase in the numbers of axons in all categories examined (myelinated, promyelin, transitional, and fetal) between levels midway along the subarachnoid course of the root and where it is apposed to but separate from the dorsal root ganglion. During maturation and throughout maturity axon totals change similarly at both levels: After a slight increase immediately postnatum, they decline sharply between 4 and 20 days due to a marked loss of unmyelinated axons. A gradual decline in myelinated axon numbers continues to 500 days. While these changes are occurring, axon numbers in all categories show a proximodistal increase throughout. The magnitude of this increase lessens with age for all but the transitional category due to a preferential decrease in numbers distally. Though these observations do not differentiate between axon branching and looping of sensory axons into the ventral root as a cause of the proximodistal increase in numbers, they tend to support the former. At each age during maturation axon proportions at proximal and distal levels correspond well for each animal, indicating that axon segregation proceeds at related rates within each root. Age changes in axon proportions within the transitional and fetal categories indicate that the postnatal stage of axon segregation results from axon loss, rather than Schwann cell proliferation.

Aging↗
PubMed1989

Axon numbers in rat oculomotor, trochlear and abducent nerves.

In the rat oculomotor, trochlear and abducent nerves, large and small classes of myelinated fibres can be clearly distinguished. Small myelinated axons comprise a larger proportion of the total in the oculomotor nerve than in the other two. Mean counts enable the myelinated preganglionic parasympathetic outflow of the oculomotor nerve to be estimated at 216 fibres. Unmyelinated fibres are most frequent in the abducent nerve and least frequent in the trochlear nerve.

Abducens Nerve↗
PubMed1988

The central-peripheral transitional regions of cranial nerves. Oculomotor nerve.

Oculomotor nerve rootlets varied more markedly in size and in transitional zone length and form than those of any other nerve studied to date. However, they could be classified into four main types, each of which was associated with a characteristic type of central-peripheral transitional zone. Type 1 rootlets emerged from the brainstem through a tongue-shaped elevation of the glia limitans. This type of central-peripheral transition is found elsewhere only in a minority of abducent rootlets (Fraher et al. 1988). Type 2 rootlets contained long segments made up entirely of central nervous tissue and were the only motor rootlets so far described to contain a segment of this kind. Type 3 rootlets were the commonest and the largest. Before leaving the brainstem they ran laterally on its surface as the emergent rootlet segments, forming plexuses with one another. These rootlets contained a unique wedge-shaped type of central tissue projection. Over its entire length one surface of this coincided with the rootlet surface and a thin tapering strip of peripheral nervous tissue extended proximally for a considerable distance into the emergent rootlet segment. Type 4 rootlets emerged from the brainstem surface obliquely and contained a glial fringe.

Animals↗