Fetal Brain Transplant: Reduction of Cognitive Deficits in Rats with Frontal Cortex Lesions

Labbe, Randy; Firl, Arthur; Mufson, Elliott J.; Stein, Donald G.

doi:10.1126/science.6683427

Cited by 170 publications

(63 citation statements)

References 15 publications

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“…Rats with transplants of E19 frontal cortex tissue into the lesioned cortex showed significant recovery in DSA, compared with lesion-only controls, 5 d after the operation. Such rapid recovery could be attributed to the release of trophic or other factors from the transplants into the host rather than through the formation of new transplant-host interconnections, which would not occur so rapidly (Labbe, 1983;Stein, 1988;Stein and Glasier, 1995). In an additional supporting study, Stein (1988) removed the transplants in one group of rats and found that the performance on DSA 3 months after surgery was not impaired in these rats.…”

Section: Discussionmentioning

confidence: 88%

“…For example, Stein and colleagues (Labbe, 1983;Stein, 1988) showed that lesions of the frontal cortex in adult rats lead to an impairment in a delayed spatial alternation T-maze task (DSA). Rats with transplants of E19 frontal cortex tissue into the lesioned cortex showed significant recovery in DSA, compared with lesion-only controls, 5 d after the operation.…”

Section: Discussionmentioning

confidence: 99%

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Hippocampal Tissue Transplants Reverse Lesion-Induced Spatial Memory Deficits in Zebra Finches (Taeniopygia guttata)

1997

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The avian hippocampal formation (Hf ) plays an important role in spatial memory for food storing. Here we examined the effects of excitotoxic lesions of the Hf and subsequent neural transplantation on a one-trial associative memory task in zebra finches. The results showed (1) that small ibotenic acid lesions of the dorsal Hf of zebra finches produced significant spatial memory impairments compared with controls, sham-lesioned birds, and prelesion performance; and (2) that Hf-lesioned birds given transplants of embryonic hippocampal (H) tissue, but not those given transplants of embryonic anterior telencephalon (AT ) tissue, showed a significant reversal of the performance deficits on the spatial memory task. Lesioned-only birds and lesioned birds given H or AT transplants that did not survive did not show behavioral improvement. Sham-lesioned and untreated control birds maintained good performance throughout the experiment. The H and AT transplants were found to be growing partially within the Hf and partially within the underlying ventricle. The transplants appeared healthy and contained neurons with beaded and unbeaded fibers (shown by immunohistochemistry with antibodies to parvalbumin, substance P, and a 200 kDa neurofilament protein). Blood vessels and erythrocytes were also present within the transplants. The results show that neural transplants can survive within the bird brain and that small lesions of the Hf produce significant spatial memory deficits that can only be reversed by surviving homologous H transplants, and not by heterologous telencephalon transplants.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Hippocampal Tissue Transplants Reverse Lesion-Induced Spatial Memory Deficits in Zebra Finches (Taeniopygia guttata)

1997

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“…Although the trophic graft mechanisms in other transplant models may account for some graft effects (38)(39)(40), available rodent models of HD show that the implanted striatal neurons can substitute for the damaged striato-pallidal neuronal connections (23)(24)(25)(26)(27). Physiological (15)(16)(17), neurochemical (41,42), and anatomical studies (23)(24)(25)(26)(27) suggest that a partial restoration of striatal input and output circuitry by implanted striatal neurons can occur.…”

Section: Discussionmentioning

confidence: 99%

Intrastriatal transplantation of cross-species fetal striatal cells reduces abnormal movements in a primate model of Huntington disease.

Hantraye

Riché

Mazière

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Huntington disease is a neurological movement disorder involving massive neuronal death in the caudate-putamen region of the brain. Neither preventive nor curative therapy exists for this disease. The implantation of cross-species striatal neural precursor cells into the lesioned striatum of nonhuman primates (baboons) reduced the abnormal movements seen in the disease model. These abnormal movements reappeared after immunological rejection of the implanted striatal cells and were not modified by transplantation with nonstriatal cells. These findings encourage further experimentation toward the use of cell sources other than human fetal cells in a potential clinical application to Huntington disease.Huntington disease (HD) evolves over several years with a continuous deterioration of the patient's condition. The motor and cognitive symptoms are associated with neuronal loss in the caudate-putamen, cerebral cortex, globus pallidus, and substantia nigra (1-5). The neuropathological changes in HD are dominated by the severe atrophy, neuronal cell loss, and astrocytic reaction in the caudate-putamen complex (striatum). By intrastriatal application of the neurotoxin ibotenic acid (IA), we have created a striatal pathology similar to HD in the baboon to evaluate therapeutic strategies, such as neuronal implantation (6). Intrastriatal injections of the glutamate receptor agonist IA and other glutamate agonists cause severe neuronal loss of striatal output neurons but spare axons of passage and striatal afferents, a characteristic pathological feature of HD (6-10). The many neuropathological and neurochemical similarities between such striatal lesions in the rat brain and alterations found in the brain of choreic patients have suggested a role for glutamate receptor agonists in the neurodegenerative mechanisms underlying HD (8,(10)(11)(12). Previous studies have utilized intrastriatal injections of IA, quinolinic, or kainic acid to produce a primate model of HD (6,13,14). Whatever the toxin used, the primates receiving such striatal lesions all display a variety of abnormal movements similar to the symptoms observed in HD patients, including dyskinesia, orofacial dyskinesia, chorea, and dystonia. These findings contrast sharply with previous rat models where involuntary choreiform movements have not been described (15)(16)(17)(18)(19)(20). We therefore used a primate model of HD to evaluate whether striatal cell replacement in the degenerated striatum could ameliorate the characteristic motor symptoms observed. We also investigated whether such symptoms would reappear after removal of immunosuppressive treatment and if implanted nonstriatal neural precursor cells could have a beneficial effect. MATERIALS AND METHODSWe performed intrastriatal stereotaxic injections of IA into the right caudate-putamen complex of 15 baboons. Six weeks later, 5 of these animals received fetal rat striatal cells by injection into the lesioned caudate-putamen. In addition to these 5 transplanted animals a 6th baboon received a contro...

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“…The behavioral deficits associated with damage to the nigrostriatal system, fimbria-fornix or frontal cortex have been reported to be diminished by implanting fetal dopaminergic neurons, fetal septal or frontal cortical tissue, respectively, into the lesion sites (Bjorklund and Stenevi, 1979b;Dunnett et al, 1982;Labbe et al, 1983). In recent experiments by Gage et al (1983), transplantation of dopaminergic neurons from the fetal substantia nigra into the caudate-putamen of old rats effectively restored age-dependent decline in motor coordination.…”

Section: Recovery O F Declined Ovarian Function In Agedmentioning

confidence: 99%

Recovery of declined ovarian function in aged female rats by transplantation of newborn hypothalamic tissue.

Matsumoto

Kobayashi

Murakami

et al. 1984

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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Fetal Brain Transplant: Reduction of Cognitive Deficits in Rats with Frontal Cortex Lesions

Cited by 170 publications

References 15 publications

Hippocampal Tissue Transplants Reverse Lesion-Induced Spatial Memory Deficits in Zebra Finches (Taeniopygia guttata)

Hippocampal Tissue Transplants Reverse Lesion-Induced Spatial Memory Deficits in Zebra Finches (Taeniopygia guttata)

Intrastriatal transplantation of cross-species fetal striatal cells reduces abnormal movements in a primate model of Huntington disease.

Recovery of declined ovarian function in aged female rats by transplantation of newborn hypothalamic tissue.

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