Summary
The survival and function of cross-species (mouse-to-rat) grafts of fetal mesencephalic dopamine (DA) neurons, implanted as a cell suspension in the striatum of rats with lesions of the mesostriatal DA system, have been studied in animals with and without immunosuppression induced by Cyclosporin A (CyA). At 6 weeks after grafting 3 out of 7 non-CyA treated animals showed some degree of graft survival and variable functional compensation. In those three animals an average of 92 DA neurons per graft was counted. In the grafted animals treated with daily CyA injections, all grafts survived and produced partial or complete functional compensation, and they had an average of 557 DA neurons per graft. It is concluded that intracerebral graft survival and function can be greatly improved by CyA treatment and that the immunological protection of neural transplants in the brain is only partial.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abercrombie M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94: 239–247
Barker CF, Billingham RE (1977) Immunologically privileged sites. Adv Immunol 25: 1–54
Björklund A, Stenevi U, Dunnett SB, Gage FH (1982) Crossspecies neural grafting in a rat model of Parkinson's disease. Nature 298: 652–654
Björklund A, Stenevi U, Schmidt RH, Dunnett SB, Gage FH (1983) Intracerebral grafting of neuronal cell suspensions. II. Survival and growth of nigral cells implanted into different brain sites. Acta Physiol Scand (Suppl) 522: 9–18
Björklund A, Stenevi U (1984) Intracerebral neural implants: neuronal replacement and reconstruction of damaged circuitries. Ann Rev Neurosci 7: 279–308
Bragin AG, Vinogradova OS (1981) Homo- and hetero-specific transplantation of embryonal central nervous tissues. Bull Exp Biol Med 10: 486–489 (in Russian)
Brundin P, Isacson O, Björklund A (1985) Monitoring of cell viability in suspensions of embryonic CNS tissue and its use as a criterion for intracerebral graft survival. Brain Res 331: 251–259
Daniloff JK, Wells J, Ellis J (1984) Cross-species septal transplants; recovery of choline acetyltransferase activity. Brain Res 324: 151–154
Daniloff JK, Low WC, Bodony RP, Wells J (1985) Cross-species neural transplants of embryonic septal nuclei to the hippocampal formation of adult rats. Exp Brain Res 59: 73–82
Homan WP, Williams KA, Fabre JW, Millard PR, Morris PJ (1981) Prolongation of cardiac xenograft survival in rats receiving cyclosporin A. Transplant Proc 31: 164–166
Inoue H, Kohsaka S, Yoshida K, Ohtani M, Toya S, Tsukada Y (1985) Cyclosporin A enhances the survivability of mouse cerebral cortex grafted into the third ventricle of rat brain. Neurosci Lett 54: 85–90
Lorén I, Björklund A, Falck B, Lindvall O (1980) The aluminum-formaldehyde (ALFA) method for improved visualization of catecholamines and indoleamines. I. A detailed account of the methodology for central nervous tissue using paraffin, cryostat or vibratome sections. J Neurosci Meth 2: 277–300
Low WC, Lewis PR, Bunch ST (1983) Embryonic neural transplants across a major histocompatability barrier: survival and specificity of innervation. Brain Res 262: 328–333
Low WC, Daniloff JK, Bodony RP, Wells J (1985) Cross-species transplants of cholinergic neurons and the recovery of function. In: Björklund A, Stenevi U (eds) Neural grafting in the mammalian CNS. Elsevier Science Publishers B.V., Amsterdam, pp 575–584
Mason DW, Charlton HM, Jones A, Parry DM, Simmonds SJ (1985) Immunology of allograft rejection in mammals. In: Björklund A, Stenevi U (eds) Neural grafting in the mammalian CNS. Elsevier Science Publishers B.V., Amsterdam, pp 91–98
Murphy JB, Sturm E (1983) Conditions determining the transplantability of tissues in the brain. J Exp Med 38: 183–197
Raju S, Grogan JB (1977) Immunologic study of the brain as a priviledged site. Transplant Proc 9: 1187–1191
Schmidt RH, Björklund A, Stenevi U, Dunnett SB, Gage FH (1983) Intracerebral grafting of neuronal cell suspensions. III. Activity of intrastriatal nigral suspension implants as assessed by measurements of dopamine synthesis and metabolism. Acta Physiol Scand (Suppl) 522: 19–28
Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigro-striatal dopamine system. Brain Res 24: 4865–4893
Vinogradova OS, Bragin AG, Kitchigina VF (1985) Spontaneous and evoked activity of neurons in intrabrain allo- and xenografts of the hippocampus and septum. In: Björklund A, Stenevi U (eds) Neural grafting in the mammalian CNS. Elsevier Science Publishers B.V., Amsterdam, pp 409–419
Zalewski A, Gulati AK (1984) Survival of nerve allografts in sensitized rats treated with cyclosporin A. J Neurosurg 60: 828–834
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brundin, P., Nilsson, O.G., Gage, F.H. et al. Cyclosporin A increases survival of cross-species intrastriatal grafts of embryonic dopamine-containing neurons. Exp Brain Res 60, 204–208 (1985). https://doi.org/10.1007/BF00237035
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00237035