Biomedical subjects

John Fraher

Publications and source records attributed to John Fraher.

2 recordsLinked to original sources

PubMed2004

The developing cervical spinal ventral commissure of the rat: a highly controlled axon-glial system.

The floor plate of the neural tube is of major importance in determining axonal behaviour, such that, having crossed, decussating axons do not cross back again. The ventral commissure (VC) of the spinal cord forms immediately ventral to the floor plate shortly after neural tube closure. It is the principal location in which decussating axons cross the midline. It is probably also of major importance in neural tube development, but has received relatively little attention. This study analyses the growth and development of the rat VC and also axon-glial relationships within it throughout the crucial prenatal period of extensive transmedian axon growth, when key biochemical interactions between the two tissues are taking place. The morphometric, stereological and immunohistochemical methods used show that the axonal and glial populations remain in a finely balanced equilibrium throughout a period of almost a hundred-fold growth of both elements. At all stages axons are highly segregated into small bundles of constant size by glial processes, to which they are closely apposed. Thus, glial-axon contact is remarkably precocious, uniquely intimate and persists throughout VC development. This suggests that the relationship between the two tissues is highly controlled through interactions between them. The VC is likely to be the physical basis of a second set of glial-axonal interactions, namely, those which are well known to influence axon crossing behaviour. In mediating these, the extensive axon-glial contact is an ideal arrangement for molecular transfer between them, and is probably the substrate for altering axon responsiveness and ensuring reliable transmedian decussation. The VC is therefore a segregating matrix temporally and spatially specialised for a range of key developmental axon-glial interactions.

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PubMed2002

Axons and glial interfaces: ultrastructural studies.

At most vertebrate nerve transitional zones (TZs) there is a glial barrier which is pierced by axons passing between the CNS and PNS. Myelinated axons traverse this in individual tunnels. The same is true of larger non-myelinated axons. This holds widely among the vertebrates, for example, the large motor axons of the sea-lamprey Petromyzon (which also possess TZ specializations not found in mammals). Smaller non-myelinated axons traverse the TZ glial tunnels as fascicles and so the barriers are correspondingly less comprehensive for them. Accordingly, in nerves composed of non-myelinated axons, such as the vomeronasal or the olfactory, a TZ barrier stretching across the nerve is effectivelyabsent. The chordateAmphioxus differsfrom the vertebrates in lacking a TZ barrier throughout. Invertebrates also lack glial barriers at the TZs between ganglia and interconnecting nerve trunks. The glial barrier at the dorsal spinal root TZ (DRTZ) has considerable value for analysing protocols aimed at achieving CNS regeneration, because it provides a useful model of the gliotic reaction at sites of CNS injury. Also, it is especially amenable to morphometric analysis, and so enables objective quantification of different protocols. Being adjacent to the subarachnoid space, it is accessible for experimental intervention. The DRTZ was used to investigate the value of neurotrophin 3 (NT3) in promoting axon regeneration across the TZ barrier and into the CNS following dorsal root crush. It promoted extensive regeneration and vigorous non-myelinated axonal ensheathment. On average, around 40% of regenerating axons grew across the interface, compared with virtually none in its absence. These may have traversed the interface through loci occupied by axons prior to degeneration. Many regenerating axons became myelinated, both centrally and peripherally.

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