Transplantation of fetal cortex to the brain of newborn rats: A retrograde fluorescent analysis of callosal and thalamic projections from transplant to host

Castro, Anthony J.; Zimmer, Jens; Sunde, Niels; Bold, E. L.

doi:10.1016/0304-3940(85)90591-9

Cited by 55 publications

(12 citation statements)

References 16 publications

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“…The histological analysis showed that the transplants had grown to fill the lesion cavity, and they displayed characteristic whorls and bands of cells separated by fibrous septae. The general histological appearance of the neocortical transplants, as observed in toluidin blue stained sections, was accordingly similar to that previously described (Castro et al 1985(Castro et al , 1988(Castro et al , 1989Stanfield and O'Leary 1985;Chang et al 1986). …”

Section: Transplant Survival and Histologysupporting

confidence: 84%

“…lb). This was taken as evidence that the transplants had become innervated by AChE-positive fibers from cholinergic BFB neurons, as also previously shown by Sofroniew et al (1986) and Castro et al (1985Castro et al ( , 1988Castro et al ( , 1989.…”

Section: Transplant Survival and Histologysupporting

confidence: 59%

“…Tissue blocks consisting of approximately 2-3 mm 3 of frontal cortex were excised from the frontolateral aspect of the telencephalic vesicle, as described previously by Castro et al (1985Castro et al ( , 1988). The donor tissue was then aspirated into a glass cannula mounted on a 50 ~tl Hamilton syringe and injected into the previously made frontal cortical lesion cavities of the 10 recipient animals which at the same time had been prepared for the receipt of the transplants.…”

Section: Transplantationmentioning

confidence: 99%

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Axotomized, adult basal forebrain neurons can innervate fetal frontal cortex grafts: A double fluorescent tracer study in the rat

et al. 1990

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The ability of axonal regeneration of identified adult basal forebrain (BFB) neurons was examined after homotopic grafting of fetal neocortical tissue to a lesion cavity in the frontal neocortex. Using a four step experimental procedure, adult rats first received an injection of the fluorescent dye Fluoro-Gold (FG) into the sensorimotor cortex in order to label those neurons with projections to the area by retrograde axonal transport. After one week the injection area was removed by aspiration, leaving a cavity in the neocortex. One week later a block of fetal (E14) frontal cortical tissue was placed in the cavity. The animals were then allowed to survive for 6 weeks before a second fluorescent tracer, Nuclear Yellow (NY), was injected into the transplant. The animals were sacrificed 24 h later and analyzed by fluorescence microscopy. Both single labeled, FG and NY containing neurons and double labeled neurons containing both tracers were found in the BFB. The results demonstrate that adult BFB neurons can reestablish cortical projections into fetal cortical grafts (double labeled neurons), and they suggest that other BFB neurons, not initially innervating the lesioned cortical area, have sprouted into the transplant (NY labeled neurons).

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Section: Transplant Survival and Histologysupporting

confidence: 84%

Section: Transplant Survival and Histologysupporting

confidence: 59%

Section: Transplantationmentioning

confidence: 99%

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Axotomized, adult basal forebrain neurons can innervate fetal frontal cortex grafts: A double fluorescent tracer study in the rat

et al. 1990

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“…For example, retinae transplanted onto the surface or into the parenchyma of the midbrain exhibit a target directed outgrowth towards the superior colliculus in a highly specific manner Lund, 1987, 1990). Fetal cortical (Floeter and Jones, 1984;Castro et al, 1985;Stanfield and O'Leary, 198.5;Heffner et al, 1990) and hippocampal neurons (Sunde et al, 1984;Zimmer et al, 1987) transplanted into neonatal animals can establish organotypic afferent and efferent connections with the host brain restoring part of the normal neuronal circuitry.…”

Section: Discussionmentioning

confidence: 99%

“…In developing animals the ability of fetal CNS grafts to establish long axonal pathways has been well documented. In particular, highly organized and specific axonal projections have been demonstrated from grafts of fetal cortex implanted into the cerebral cortex (Floeter and Jones, 1984;Castro et al, 1985;Stanfield and O'Leary, 198.5;Hefner et al, 1990), from grafts of hippocampal neurons in the hippocampus (Sunde et al, 1984;Zimmer et al, 1987) and for retinal ganglion cells in the retinotectal system Lund, 1987, 1990;Lund et al, 1988) in neonatal recipients. A similar developmental plasticity has been demonstrated for fetal spinal cord grafts implanted into the neonatally lesioned spinal cord associated with signs of functional restoration (Iwashita et al, 1994).…”

Section: Reconstructionmentioning

confidence: 99%

Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. I. Evidence for anatomical reconstruction of the nigrostriatal pathway

et al. 1995

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Reconstruction of the nigrostriatal pathway by long axon growth derived from dopamine-rich ventral mesencephalic (VM) transplants grafted into the substantia nigra may enhance their functional integration as compared to VM grafts implanted ectopically into the striatum. Here we report on a novel approach by which fetal VM grafts are implanted unilaterally into the substantia nigra (SN) of 6-hydroxydopamine (6- OHDA)-lesioned neonatal pups at postnatal day 3 (P3) using a microtransplantation technique. The results demonstrate that homotopically placed dopaminergic neurons survive and integrate well into the previously 6-OHDA-lesioned neonatal SN region. Moreover, the tyrosine hydroxylase (TH)-positive neurons extended axons rostrally along the white matter tract of the internal capsule closely following the course of the original nigrostriatal pathway. The graft reestablished a TH-positive axon terminal network in the ipsilateral caudate-putamen, with the highest density in the medial and central parts. Retrograde labeling with Fluoro-Gold from the host striatum demonstrated that most of the transplant neurons giving rise to the graft-derived fiber outgrowth were TH-positive, but revealed also a small proportion of projecting neurons which were TH-negative. Amphetamine-induced striatal Fos expression was normalized in the caudate-putamen ipsilateral to the intranigral VM grafts, showing hyperexpression in some areas of the striatum, and the apomorphine- induced Fos expression seen in the 6-OHDA-lesioned animals was completely reversed on the grafted side. These findings indicate that the graft-derived dopaminergic reinnervation of the striatum is functional. The microtransplantation strategy may provide new avenues for the exploration of morphological and functional integration of fetal dopamine neurons in the nigrostriatal system and give new insights into the mechanisms controlling long-distance axon growth in the brain.

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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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Transplantation of fetal cortex to the brain of newborn rats: A retrograde fluorescent analysis of callosal and thalamic projections from transplant to host

Cited by 55 publications

References 16 publications

Axotomized, adult basal forebrain neurons can innervate fetal frontal cortex grafts: A double fluorescent tracer study in the rat

Axotomized, adult basal forebrain neurons can innervate fetal frontal cortex grafts: A double fluorescent tracer study in the rat

Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. I. Evidence for anatomical reconstruction of the nigrostriatal pathway

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

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