Embryonic motoneurons grafted into the adult CNS can differentiate and migrate

Demierre, B.; Martinou, Jean‐Claude; Kato, A.C.

doi:10.1016/0006-8993(90)91391-s

Cited by 18 publications

(4 citation statements)

References 21 publications

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“…A similar migration to the contralateral side was observed with motoneurons grafted into the striatum (Ruiz-Flandes et al, 1993) and with astrocytes that were placed originally into deep neocortical layers (Lund et al, 1993). The ability of grafted nerve and glial cells to migrate and to integrate into the neural network of the recipient has been described in the past for nerve and glial cells (see, e.g., Finsen and Zimmer, 1986;Privat et al, 1986;Goldberg and Bernstein, 1988;McConnell, 1988;Kawamura et al, 1988;Sieradzan and Vrbová, 1989;Demierre et al, 1990;Sotelo et al, 1990;Lund at al., 1993;Warrington et al, 1993;Gumpel, 1994;Lois and Alvarez-Buylla, 1994) for both short-and long-distance migration. The latter seems to occur mainly after interspecies transplantations, whereas allogenic grafts tend to remain in the vicinity of the region of implantation (Wells et al, 1987).…”

Section: Fate Of the Grafted Mouse Cells In The Kitten Cnssupporting

confidence: 57%

Remodeling of lesioned kitten visual cortex after xenotransplantation of fetal mouse neopallium

Ourednik

Mitchell

1998

J. Comp. Neurol.

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Remodeling of the mechanically injured cerebral cortex of kittens was studied in the presence of a neural xenograft taken from mouse fetuses. Solid neural tissue from the neopallium of a 14-day-old fetus was transferred into a cavity prepared in visual cortical area 18 of 33-day-old kittens. Injections of bromodeoxyuridine (BrdU) were used to monitor postoperative cell proliferation. Two months after transplantation, the presence of graft tissue in the recipient brain was assessed by Thy-1 immunohistochemistry. Antibodies specific for neurons, astrocytes, and oligodendrocytes and hematoxylin staining for endothelial cells were used for the characterization of proliferating (BrdU+) cells. The following were the major observations: 1) Of ten transplanted kittens, four had the cavity completely filled with neural tissue that resembled the intact cerebral cortex in its cytoarchitecture, whereas, in four other kittens, the cavity was partially closed. In two kittens, the cavity remained or became larger, which was also the case with all four sham-operated (lesioned, without graft) animals. 2) A substantial part of the remodeled tissue was of host origin. Only a few donor cells survived and dispersed widely in the host parenchyme. 3) In the remodeled region of transplanted animals, the densities of nerve, glial, and endothelial cells were similar to those in intact animals. 4) Cell proliferation increased after transplantation but only within a limited time, because, 2 months after the operation, the number of mitotic cells in the grafted cerebral cortex did not differ from that in intact controls. Our data suggest that the xenograft evokes repair processes in the kitten visual cortex that lead to structural recovery from a mechanical insult. The regeneration seems to rely on a complex interplay of many different mechanisms, including attenuation of necrosis, cell proliferation, and immigration of host cells into the wounded area.

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Section: Fate Of the Grafted Mouse Cells In The Kitten Cnssupporting

confidence: 57%

Remodeling of lesioned kitten visual cortex after xenotransplantation of fetal mouse neopallium

Ourednik

Mitchell

1998

J. Comp. Neurol.

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“…On the other hand, the fact that migration of grafted cells has also been reported in some cases in adult hosts (see, e.g., Alvarado-Mallart, 1986, 1987;Demierre et al, 1990) suggests that some intrinsic migratory programs may be retained in the implanted embryonic neurons during a limited period of their ontogenetic development, possibly coinciding with a short time span following their birth (which, for cholinergic neurons in the basal forebrain, lies between E l 3 and E15; see Semba, 1992).…”

Section: Growth Properties Of the Intraseptal Graftsmentioning

confidence: 96%

Extensive reinnervation of the hippocampus by embryonic basal forebrain cholinergic neurons grafted into the septum of neonatal rats with selective cholinergic lesions

et al. 1996

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Reconstruction of the septohippocampal pathways by axons extending from embryonic cholinergic neuroblasts grafted into the neuron-depleted septum has been explored in the neonatal rat by using a novel lesioning and grafting protocol. Neonatal ablation of the basal forebrain cholinergic projection neurons, accompanied by extensive bilateral cholinergic denervation of the hippocampus and neocortex, was produced at postnatal day (PD) 4 by 192 immunoglobulin (IgG)-saporin intraventricularly. Four days later, cholinergic neuroblasts (from embryonic day 14 rats) were implanted bilaterally into the neuron-depleted septum by using a microtransplantation approach. The results show that homotopically implanted septal neurons survive and integrate well into the developing septal area, extending axons caudally along the myelinated fimbria-fornix and supracallosal pathways that are able to reach the appropriate targets in the denervated hippocampus and cingulate cortex as early as 4 weeks postgrafting. Moreover, the laminar innervation patterns established by the graft-derived axons closely resembled the normal ones and remained essentially unchanged up to at least 6 months, which was the longest postoperative time studied. The reinnervating fibers restored tissue choline acetyltransferase activity (up to 50% of normal) in the dorsal hippocampus and the parietooccipital cortex. Retrograde labeling with Fluoro-Gold from the host hippocampus combined with immunocytochemistry confirmed that most of the projecting neurons, indeed, were cholinergic. The results suggest that the graft-host interactions that are necessary for target-directed axon growth are present in the septohippocampal system during early postnatal maturation. Thus, the present approach may contribute to overcome the functional limitations inherent in the use of ectopically placed intrahippocampal transplants.

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“…One such option is to label the graft prior to implantation, and a number of tracers have been explored for this purpose. These include fluorescent latex microspheres (7,19), gold-filled viruses (2), horseradish peroxidase (13), 1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine perchlorate (DiI) (10,19), fluorescent tracers and Phaseolus vulgaris leucoagglutinin (PHA-L) (19), as well as the use of retroviral mediated gene transfer of a reporter gene (19). The application of these techniques varies depending on the goal of the experiment because some only label graft neurons (fluorescent latex microspheres, fluorescent tracers, and gold-filled viruses) other label both cells and neurites (HRP, DiI, PHA-L, and retroviral mediated gene transfer).…”

Section: Introductionmentioning

confidence: 99%

Biotinylated Dextran Amine as a Marker for Fetal Hypothalamic Homografts and Their Efferents

Nelms

LeSauter

Silver

et al. 2002

Experimental Neurology

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We have explored the use of biotinylated dextran amine (BDA) as a marker for labeling fetal brain grafts and their connections with the host. As a model system we used transplantation of the hamster suprachiasmatic nucleus, the site of an endogenous biological clock governing circadian rhythms. Similar transplants into arrhythmic hosts have been shown to restore behavioral function with a period specific to the donor. For locomotor rhythms, efferent connections are not necessary. For other responses, including endocrine rhythms, efferent connections may be necessary. In order to visualize homografts and their efferents, injections of BDA, an anterograde tracer, were made into the anterior hypothalamic (AH) region containing the SCN or into the dorsal cortex (CTX) of fetal hamster brains. The fetal AH or CTX was microdissected out and stereotaxically implanted into the third ventricle of intact, adult hamsters. After 2, 4, 8, or 12 weeks, hosts were sacrificed and their brains were processed for detection of BDA by either histochemistry or immunofluorescence. BDA intensely labeled graft neurons, their dendrites, and axons with minimal or no spread to the adjacent host brain. Labeled graft axons could be followed for long distances (>1 mm) into the host brain and graft-derived varicosities formed close contacts with host neurons. BDA-labeled graft neurons, located at the perimeter of the graft, also extended dendrite-like processes into the host parenchyma. We conclude that BDA is a useful marker for fetal homografts and their efferents for survival times of less than 2 months.

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Embryonic motoneurons grafted into the adult CNS can differentiate and migrate

Cited by 18 publications

References 21 publications

Remodeling of lesioned kitten visual cortex after xenotransplantation of fetal mouse neopallium

Remodeling of lesioned kitten visual cortex after xenotransplantation of fetal mouse neopallium

Extensive reinnervation of the hippocampus by embryonic basal forebrain cholinergic neurons grafted into the septum of neonatal rats with selective cholinergic lesions

Biotinylated Dextran Amine as a Marker for Fetal Hypothalamic Homografts and Their Efferents

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