Multiple Transplants of Fetal Striatal Tissue in the Kainic Acid Model of Huntington's Disease

Sanberg, Paul R.; Henault, Mark A.; Hagenmeyer-Houser, Starr H.; Giòrdano, Magda; Russell, Kristanne H.

doi:10.1111/j.1749-6632.1987.tb23738.x

Cited by 13 publications

(5 citation statements)

References 5 publications

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“…The observations reported here confirm the presence of a macroscopic modular architecture in fetal striatal grafts and a remarkable phenotypic resemblance of many neuronal constituents in the grafts to neuronal constituents found in normal postnatal and mature striatum (Isacson et al, 1984(Isacson et al, , 1985(Isacson et al, , 1987Pritzel et al, 1986;Walker et al, 1987;Deckel and Robinson, 1987;Sanberg et al, 1987;Graybiel et al, 1987a;Roberts and DiFiglia, 1988;DiFiglia et al, 1988). The phenotypic resemblance inferred from the markers screened does not necessarily imply identity but does suggest that at the cellular level many antigen characteristics expressed by neurons in the grafts were like those expressed by neurons in normal striatal tissue.…”

Section: Discussionsupporting

confidence: 81%

“…Fetal striatal grafts provide a potentially powerful experimental system for studying the determinants of neutotransmitter-specific neural development. Several research groups have demonstrated that cells derived from the embryonic ganglionic eminence survive transplantation to the striatum of the adult rat and express a variety of neurotransmitter-and receptor-related markers characteristic of normal striatal tissue (Isacson et al, 1984(Isacson et al, ,1985(Isacson et al, , 1987Pritzel etal., 1986;Walkeret al, 1987;Deckel and Robinson, 1987;Sanberg et al, 1987;Graybiel et al, 1987a;Roberts and DiFiglia, 1988). In the most systematic study so far, Isacson et al (1987) have shown that such grafts develop a compartmentalized organization in which markers for neutotransmitter-related compounds are arranged in macroscopic patches visible in sections through the grafts.…”

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confidence: 99%

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Intrastriatal grafts derived from fetal striatal primordia. I. Phenotypy and modular organization

1989

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Fetal striatal grafts display a striking modularity of composition. With acetylcholinesterase (AChE) histochemistry, the tissue of such grafts can be divided into regions with strong AChE staining of the neuropil and regions in which AChE staining of the neuropil is weak. In the experiments reported here, we reexamined the nature of this modularity. Striatal grafts were made by injecting dissociated cells of E15 ganglionic eminence into the striatum of adult rats, which 7 days before had recived intrastriatal deposits of ibotenic acid. Some donors had been exposed to 3H-thymidine at E11-E15. After 9-17 month survivals, the anatomical organization of the grafts was studied by histochemistry, immunohistochemistry, and autoradiography. In every graft, the AChE-rich regions formed patches (P regions) in a larger AChE-poor surround (NP regions). Neurons labeled with 3H-thymidine appeared in both P and NP regions, suggesting that donor cells were distributed in each type of region and that neither type of tissue, P or NP, was composed exclusively of host tissue. In the AChE-rich P regions, markers characteristic of normal perinatal and mature rat striatum were expressed by medium-sized cells: calcium-binding protein (calbindin D28k) immunostaining, metenkephalin (mENK) immunostaining, and, more rarely, somatostatin (SOM) immunostaining. In the NP regions, however, medium-sized cells expressing calbindin and mENK immunostaining were very rare, and there was an abundance of neuronal types not found in normal mature striatal tissue. These included (1) large, multipolar, calbindin-positive neurons with well-ramified, densely stained dendrites, (2) large, SOM-positive neurons with prominent dendritic trees, and (3) mENK-positive cells smaller than typical striatal, medium-sized, mENK-immunoreactive neurons. In Nissl stains, the AChE-rich P regions resembled the normal striatum of mature animals, whereas the AChE-poor NP regions did not. These findings suggest that the P regions of fetal striatal grafts achieve a phenotypy similar to that of normal striatum at maturity and during much of postnatal development. The dominant expression of perikaryal calbindin-like immunoreactivity in the P regions further suggests that these zones have a high proportion of tissue resembling striatal matrix. By contrast, expression of marker antigens in the NP zones of the grafts suggests that these zones are predominantly composed of nonstriatal tissue or that they have the phenotypy of immature striatum intermixed with some nonstriatal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionsupporting

confidence: 81%

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confidence: 99%

Intrastriatal grafts derived from fetal striatal primordia. I. Phenotypy and modular organization

1989

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“…Concrete evidence detailing functional and neuroanatomical recovery following fetal ventral mesencephalic cell transplantation has been reported in PD patients 5,6 . These promising developments in neural transplantation for PD and the demonstration of survival and efficacy of fetal striatal transplants into animal models of Huntington's disease (HD) 7,8 may validate clinical trials of neural transplantation for HD. Recently, Peschanski and colleagues 9 outlined the rationale for proceeding with clinical trials of fetal neural transplantation as a treatment modality for HD.…”

Section: Neural Transplantation and Excitotoxic Models Of Huntington'mentioning

confidence: 99%

“…Selective excitotoxic compounds [ e.g. , kainic acid (KA), ibotenic acid (IA), and quinolinic acid (QA)] have been used extensively to successfully create lesions in the striatum (or caudate‐putamen) in humans, which is the primary brain structure damaged in HD 10 and to produce neurobehavioral symptoms similar to HD 7,8 . These excitotoxic animal models have also been used to characterize the potential effects of neural tranplantation.…”

Section: Neural Transplantation and Excitotoxic Models Of Huntington'mentioning

confidence: 99%

“…These excitotoxic animal models have also been used to characterize the potential effects of neural tranplantation. Investigations have shown that rodent fetal striatum transplanted into rodents (allografts) 8,11 or primates (xenografts) 1,2 can produce recovery of function. Further, xenografts of human fetal tissue can grow and integrate in the rodent brain provided immunosuppression is given 11 .…”

Section: Neural Transplantation and Excitotoxic Models Of Huntington'mentioning

confidence: 99%

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Human Fetal Striatal Transplantation in an Excitotoxic Lesioned Model of Huntington's Disease

Sanberg

Borlongan

Koutouzis

et al. 1997

Annals of the New York Academy of Sciences

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Transplantation of fetal neural tissue into the adult brain was initially investigated to examine the developmental and regenerative capacity of the nervous systern.l2 Intrastriatal transplantation has been a major focus of neural transplantation research because of the well-characterized anatomy of the normal striatum (or caudate-putamen). With many chemically identified types of striatal neurons and fiber systems, their reaction upon lesioning and transplantation could provide essential information about factors regulating, for instance, neuronal survival and differentiation. Apart from this initial goal of investigating CNS development and plasticity, neural grafting has been demonstrated to ameliorate the functional deficits induced by various brain lesions. Accordingly, it was suggested that neural grafting might be an appropriate treatment for various neurodegenerative di~0rders.l~ NEURAL TRANSPLANTATION AND EXCITOTOXIC MODELS OF HUNTINGTON'S DISEASENeural transplantation has emerged as an alternative therapeutic modality for Parkinson's disease (PD)! Concrete evidence detailing functional and neuroanatomical recovery following fetal ventral mesencephalic cell transplantation has been reported in PD patient^.^,^ These promising developments in neural transplantation for PD and the demonstration of survival and efficacy of fetal striatal transplants into animal models of Huntington's disease (HD)'.' may validate clinical trials of neural transplantation for HD. Recently, Peschanski and colleagues9 outlined the rationale for proceeding with clinical trials of fetal neural transplantation as a treatment modality for HD. Since several other research centers worldwide have set-up clinical trials for fetal neural transplantation for HD, the implications of the evidence from animal models should be closely evaluated.

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Locomotor behavior changes induced by E-17 striatal transplants in normal rats

Hagenmeyer-Houser

Sanberg

1987

Pharmacology Biochemistry and Behavior

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Multiple Transplants of Fetal Striatal Tissue in the Kainic Acid Model of Huntington's Disease

Cited by 13 publications

References 5 publications

Intrastriatal grafts derived from fetal striatal primordia. I. Phenotypy and modular organization

Intrastriatal grafts derived from fetal striatal primordia. I. Phenotypy and modular organization

Human Fetal Striatal Transplantation in an Excitotoxic Lesioned Model of Huntington's Disease

Locomotor behavior changes induced by E-17 striatal transplants in normal rats

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