Regrowth of lesioned dorsal root nerve fibers into the spinal cord of neonatal rats (original) (raw)
Related papers
Reinnervation of the mammalian spinal cord after neonatal dorsal root crush
Journal of Neurocytology, 1988
In the adult mammal, nerve fibres do not regrow into the spinal cord after a dorsal root lesion. The elongation of dorsal root nerve fibres into the spinal cord of neonatal rats was examined: L4 and L5 dorsal roots were crushed in rat pups. After 3-6 months, the dorsal root-spinal cord junction was investigated morphologically in several long series of ultrathin cross-sections, in rats which had been operated on at birth (0-2 days 01d), axons from the lesioned roots could be followed into the CNS tissue of the spinal cord. In contrast to normal development, the usual short segment of CNS glia did not grow into the neonatally lesioned roots. Instead, the CNS-PNS border was located within the spinal cord. The nerve fibres, which were of normal diameter, had regrown across the PNS-CNS border and elongated further into the CNS environment of the spinal cord. In rats operated on at the end of the first postnatal week or later, the largest dorsal root nerve fibres were only half the size of those in unoperated animals and reinnervation of the spinal cord had not occurred. An astrocyte-dominated CNS segment had developed in these roots. The impact of an early neuronal lesion on the development of certain glia cells and their importance in the outcome of spinal cord reinnervation are discussed.
Nerve fibre regeneration across the PNS-CNS interface at the root-spinal cord junction
Brain Research Bulletin, 1989
T., S. CULLHEIM, M. RISLING AND B. ULFHAKE. Nervejibre regeneration across the PNS-CNS interface at the root-spinal cordjunction. BRAIN RES BULL 22(l) 93-102, 1989.-Root-spinal cord regeneration was investigated in immature and adult rats. The elongation in the dorsal root of regrowing dorsal root axons, rerouted ventral root nerve fibres (cholinergic neurons) or hypogastric nerve fibres (catecholaminergic neurons) is impeded as they meet the astrocyte dominated CNS tissue of the root. The establishment of synaptoid nerve terminals as the regrowing axons encounter astrocytes indicates a mechanism for growth inhibition other than a physical impediment in the CNS environment. The glial cells of the CNS segment in the root are influenced by the type of regenerating nerve fibres in terms of maintenance, multiplication and phenotypic expression. After a dorsal root lesion in the neonatal rat several root axons may reinnervate the spinal cord. In these rats, the normal establishment of a CNS root segment has been disrupted and the PNS-CNS border is situated central to the root-spinal cord junction. Implantation of cut dorsal roots into the spinal cord of adult rats results in the extension of processes from intrinsic spinal cord neurons out into the root. After implantation of avulsed ventral roots into the ventro-lateral aspect of the cord, axonal regrowth and functional restitution of a-motoneurons could be demonstrated by intracellular recordings and injections with horseradish peroxidase.
Neuroscience Letters, 1985
In an attempt to enhance spinal cord reinnervation by dorsal root neurons in the adult rat, the root was cut and implanted into the cord. Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the dorsal root ganglion in order to look for regrowth in the spinal cord. Instead of regenerated dorsal root axons, there was an occurrence of HRP-labelled spinal cord neurons in the vicinity of the implanted dorsal root. In control animals, which had been subjected to dorsal root crush, no labelled neurons or terminals were observed in the spinal cord.
Developmental Brain Research, 1988
Sciatic nerve section and ligation on the day of birth results in marked growth retardation of the rat dorsal horn. This transneuronal effect was examined in spinal cord cells that project to the brain by retrograde labelling with HRP from contralateral dorso-and ventrolateral tracts in the thoracic white matter. HRP-impregnated gel pellets were implanted in the tracts for 48-72 h to allow intense somadendritic staining of the projection cells. The results show that cells in rats whose sciatic nerve has been sectioned at birth have a mean somal area that is 40% smaller than controls. Primary dendrites are reduced from a mean of 4.1 per cell to 3.1 per cell and secondary branching is reduced by 75%. The results suggest that there was no actual cell death, only growth retardation. An intact primary afferent input apparently has a strong transneuronal trophic influence on spinal cord sensory cells projecting to the brain.
Journal of neurocytology, 1997
Following dorsal root crush, the lesioned axons regenerate in the peripheral compartment of the dorsal root, but stop at the boundary between the peripheral and the central nervous system, the dorsal root transitional zone. We have previously shown that fibres from human fetal dorsal root ganglia grafted to adult rat hosts are able to grow into the spinal cord, but were not able to specify the route taken by the ingrowing fibres. In this study we have challenged the dorsal root transitional zone astrocyte boundary with human dorsal root ganglion transplants from 5-8-week-old embryos. By tracing immunolabelled human fibres in serial sections, we found that fibres consistently grow around the dorsal root transitional zone astrocytes in laminin-rich peripheral surroundings, and extend into the host rat spinal cord along blood vessels, either into deep or superficial laminae of the dorsal horn, or into the dorsal funiculus. Human fibres that did not have access to blood vessels grew on ...
The Journal of Comparative Neurology, 1993
Dorsal root ganglion (DRG) neurons decrease their substance P (SP) synthesis after peripheral nerve lesions. Levels in the dorsal horn also decline but return to normal if regeneration is successful. In adults, when regeneration is prevented, recovery of SP in the dorsal horn is slow and incomplete, whereas in newborns, recovery is rapid and complete even though retrograde cell death of DRG neurons is greater than in adults. We have examined the mechanisms that might account for the rapid and complete recovery of SP and calcitonin-gene related peptide (CGRP) in the dorsal horn after peripheral nerve injury in newborns. Peptides were compared in the L4 and L5 DRG and spinal cord segments of normal rats and in rats surviving 6 days to 4 months after sciatic nerve section/ligation within 24 hours of birth.
Regeneration of adult dorsal root axons into transplants of embryonic spinal cord
Journal of comparative neurology, 1988
Cut dorsal root axons regenerate into transplants of embryonic spinal cord and form synapses that resemble those found in the dorsal horn of normal spinal cord. One aim of the present study was to determine whether these axons also regenerate into and establish synapses within transplants of embryonic brain. A second aim was to compare the patterns of growth in embryonic brain and spinal cord transplants. Embryonic spinal cord or brain was transplanted into the lumbar enlargement of adult Sprague-Dawley rats, the L4 or L5 dorsal root was cut, and the cut root was juxtaposed to the transplant. The transplants included whole pieces or dissociated cell suspensions of embryonic day 14 (E14) spinal cord, or whole pieces of E l 4 neocortex, E l 8 occipital cortex, E l 5 cerebellum, or E l 8 hippocampus. One month later the regenerated dorsal root axons were labeled by immunocytochemical methods to demonstrate calcitonin gene-related peptide (CGRP). CGRP-immunoreactive axons regenerated into all the transplants examined and formed synapses in the neocortex and cerebellum transplants in which they were sought. Synapses were far rarer in neocortex and cerebellum than we had observed previously in transplanted spinal cord, and the patterns of growth differed in transplants of spinal cord and brain. In solid transplants of spinal cord, regenerated axons remained relatively close to the interface with the dorsal root, branched, and formed bundles. Areas of dense ingrowth were separated by regions with few labeled axons. In transplants of brain regions, the regenerated axons were few, unbranched, and appeared as individual fibers rather than in bundles, but they were distributed widely in neocortex transplants. The results of quantitative studies confirmed these observations. The area fraction occupied by regenerated axons in solid spinal cord transplants was significantly larger than in occipital cortex or cerebellum transplants. Distribution histograms of the area occupied in transplants demonstrated that regenerated axons were distributed sparsely but homogeneously in transplants of brain, whereas spinal cord transplants were heterogeneous for regenerated axons and contained areas in which growth was dense or sparse. In contrast, several measurements of axon distribution, including area, longest axis, and length of lateral extension, indicated that CGRP-labeled axons spread more widely in occipital cortex transplants than in solid transplants of spinal cord or cerebellum. The results indicate that embryonic CNS tissues that are not normal targets support or enhance the growth of severed dorsal roots and suggest that the conditions that constitute a permissive environment for regenerating axons are relatively nonspecific. Embryonic spinal cord, the normal target of dorsal roots, appears to supply additional, more specific cues that enable regenerating axons to grow and arborize within the transplant and to establish relatively normal numbers of synapses. These cues appear to depend at least in part on the integrity of transplant structure, since growth into solid transplants of spinal cord exceeds growth into cell suspensions.
Nerve fibre regeneration across the peripheral-central transitional zone
Journal of Anatomy, 1997
Neurons cannot negotiate an elongation across the peripheral (PNS)-central nervous system (CNS) transitional zone and grow into or out of the spinal cord in the mature mammal. The astrocytic rich CNS part of the spinal nerve root is most effective in preventing regeneration even of nerve fibres from transplanted embryonic ganglion cells. Regeneration of severed nerve fibres into the spinal cord occurs when the transition zone is absent as in the immature animal. Before the establishment of a transition zone there is also new growth of neuronal processes from dorsal horn neurons distally to the injured dorsal root. Thus the experimental strategy to reestablish spinal cord to peripheral nerve connectivity has been to delete the transitional region and implant severed ventral or dorsal roots into the spinal cord. Dorsal root implantation resulted in reestablished afferent connectivity by new neuronal processes from secondary sensory neurons in the dorsal horn of the spinal cord extending into the PNS. The ability for plasticity in these cells allowed for a concurrent retention of their original rostral projection. Ventral root implantation into the spinal cord corrected deficit motor function. In a long series of experiments performed in different species, the functional restitution was demonstrated to depend on an initial regrowth of motor neuron axons through spinal cord tissue (CNS). These findings have led to the design of a new surgical strategy in cases of traumatic spinal nerve root injuries.