Human dorsal root ganglion neurons from embryonic donors extend axons into the host rat spinal cord along laminin-rich peripheral surroundings of the dorsal root transitional zone (original) (raw)
Related papers
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 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.
Regrowth of lesioned dorsal root nerve fibers into the spinal cord of neonatal rats
Neuroscience Letters, 1987
In postnatal rat pups the L4 and L5 dorsal roots were lesioned. After 3~ months the spinal cord of the rats was subjected to tracing studies of regenerated dorsal root axons with transganglionically transported horseradish peroxidase (HRP) and immunohistochemistry with antibodies to calcitonin generelated peptide (CGRP). In rats operated at birth (0-2 days old) HRP-filled profiles as well as CGRP staining were found in the outer lamina of the spinal cord dorsal horn. Signs of dorsal root nerve fiber regrowth in the spinal cord could not be found in rats which had been operated at the end of the first postnatal week or later.
Neuroscience Letters, 1991
Highly enriched cultures of Schwann cells were obtained from adult rat dorsal root ganglia and implanted (5 x 1OS-9 x l0 s cells) in the spinal cord of syngenic adult rats at the site of an acute compression lesion produced by a subdural inflatable microbatloon. These autografts survived and invaded the host tissue, reducing central cavitation and astrocytic gliosis. They dramatically promoted ingrowth of axons, the majority of which appeared to come from the dorsal roots as judged by their neuropeptide content. Invasion of the transplants by descending, e.g. aminergic fibers, was negligible at survival times of up to 4 months. Nonetheless, autologous Schwann cells, which are readily available in the host, represent a promising material for grafts into the injured spinal cord.
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.
Experimental neurology, 2004
A single fourth lumbar dorsal rootlet was transected at the entry point into the spinal cord. The nerve fibres were labelled with biotin dextran injected into the rootlet. An endogenous matrix containing olfactory-ensheathing cells (OECs) labelled with green fluorescent protein was applied to the opposing cut surfaces of the rootlet and the spinal cord, which were then brought into apposition and held in place by fibrin glue. Two weeks later, a ladderlike bridging structure has been formed by astrocytic processes growing out for about 200 -300 Am from the spinal cord. The transplanted cells remained largely confined to this area. They were elongated along the nerve axis but did not enter the spinal cord itself. Labelled dorsal root axons crossed the repaired dorsal root entry zone in alignment with the bridging astrocytic processes and the transplanted cells and then proceeded beyond the transplant to enter the grey matter of the dorsal horn and send axons both rostrally and caudally for at least 10 mm in the white matter of the ascending dorsal columns.