A Critical Review of the Current Status and Possible Developments in Brain Transplantation

  • S. Rehncrona
Part of the Advances and Technical Standards in Neurosurgery book series (NEUROSURGERY, volume 23)


Currently much interest is focussed on the possibilities for treatment of neurodegenerative disorders by transplantation of specific transmitter releasing cells to the central nervous system. The term “neurodegenerative” is used to describe disorders characterized by cell loss in the central nervous system and includes Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. They all have in common that their exact etiology and pathogenesis is unknown and that they curtail both the quality and quantity of life. They often slowly progress to a state of severe incapacitation of the sufferer with neurological symptoms related to which specific cell type(s) and neurotransmitter systems are affected. Since no therapy can be offered against the basic etiologies, the treatment, if any, is directed towards symptomatic relief (for comprehensive reviews the reader is referred to Calne 1994). The exciting progress made by biomedical science during the last two decades in understanding the basic mechanisms of growth, behaviour and function of neural transplants in the mammalian central nervous system has opened the possibility for a different and, at least in theory, curative therapeutic strategy aiming at repairing the brain (Dunnett and Björklund 1994). The concept may include possibilities for either a partial or even total recovery of function by replacement of lost cell populations to restore specific neurotransmitter systems, neural circuits or to remyelinate fibers in demyelination disorders.


Graft Survival Caudate Nucleus Adrenal Medulla Ventral Mesencephalon Transplantation Site 
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  1. 1.
    Allen GS, Burns RS, Tulipan NB, Parker RA (1989) Adrenal medullary transplantation to the caudate nucleus in Parkinson’s disease; initial results in 18 patients. Arch Neurol 46: 487–491PubMedGoogle Scholar
  2. 2.
    Anton R, Kordower JH, Maidment NT, Manaster JS, Kane DJ, Rabizadeh S, Scheuller SB, Yang J, Edwards RH, Markham CH, Bredesen DE (1994) Neural-targeted gene therapy for rodent an primate hemiparkinsonism. Exp Neurol 127: 207–218PubMedGoogle Scholar
  3. 3.
    Apuzzo MLJ, Neal JH, Waters CH, Appley AJ, Boyd SD, Couldwell WT, Wheelock VH, Weiner LP (1990) Utilization of unilateral and bilateral stereotactically placed adrenomedullary-striatal autografts in Parkinsonian humans: rationale, techniques, and observations. Neurosurgery 26: 746–757PubMedGoogle Scholar
  4. 4.
    Backlund E-O, Granberg P-O, Hamberger B, Knutsson E, Mårtensson A, Sedvall G, Seiger Å, Olson L (1985) Transplantation of adrenal medullary tissue to striatum in parkinsonism; first clinical trials. J Neurosurg 62: 169–173PubMedGoogle Scholar
  5. 5.
    Bakay RAE, Fiandanca MS, Barrow DL, Schiff A, Collins DC (1985) Preliminary report on the use of fetal tissue transplantation to correct MPTP-induced Parkinson-like syndrome in primates. Appl Neurophysiol 48: 358–361PubMedGoogle Scholar
  6. 6.
    Bakay RAE, Barrow DL, Fiandanca MS, Iuvone PM, Schiff A, Collins DC (1987) Biochemical and behavioral correction of MPTP Parkinson-like syndrome by fetal cell transplantation. Ann NY Acad Sci 495: 623–638PubMedGoogle Scholar
  7. 7.
    Bankiewicz KS, Plunkett RJ, Jacobowitz DM, Porrino L, Di Porzio U, London WT, Kopin IJ, Oldfield EH (1990) The effect of fetal mesencephalon implants on primate MPTP-induced parkinsonism. J Neurosurg 72: 231–244PubMedGoogle Scholar
  8. 8.
    Baron-Van Evercooren A, Clerin-Duhamel E, Lapie P, Glansmüller A, Lachapelle F, Gumpel M (1992) The fate of Schwann cells tansplanted in the brain during development. Dev Neurosci 14: 73–84PubMedGoogle Scholar
  9. 9.
    Benabid AL, Pollak P, Gervason C, Hoffman D, Gao DM, Hommel M, Perret JE, de Rougemont J (1991) Long-term suppression of tremor by chronic Stimulation of the ventral intemediate thalamic nucleus. Lancet 337: 403–406PubMedGoogle Scholar
  10. 10.
    Benabid AL, Pollak P, Seigneueret E, Hoffman D, Perret J (1993) Chronic VIM thalamic Stimulation in Parkinson’s disease, essential tremor and extrapyramidal dyskinesias. Acta Neurochir (Wien) [Suppl] 58: 39–44Google Scholar
  11. 11.
    Björklund A, Stenevi U, Svendgaard N-A (1976) Growth of transplanted monoaminergic neurons into the adult hippocampus along the perforant path. Nature 262: 787–790PubMedGoogle Scholar
  12. 12.
    Björklund A, Stenevi U (1979) Reconstruction of the nigrostriatal pathway by intracerebral nigral transplants. Brain Res 177: 555–560PubMedGoogle Scholar
  13. 13.
    Blakemore WF, Franklin RJM (1991) Transplantation of glial cells into the CNS. TINS 14: 323–327PubMedGoogle Scholar
  14. 14.
    Blond S, Caparros-Lefebvre D, Parker F, Assaker R, Petit H, Guieu J-D, Christaens J-L (1992) Control of tremor and involuntary movement disorders by chronic stereotactic stimulation of the ventral intermediate thalamic nucleus. J Neurosurg 77: 62–68PubMedGoogle Scholar
  15. 15.
    Bondareff W, Mountjoy CQ, Roth M (1982) Loss of neurons of origin of the adrenergic projection to the cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology 32: 164–168PubMedGoogle Scholar
  16. 16.
    Browder EJ (1948) Section of the fibers of the anterior limb of the internal capsule in parkinsonism. Am J Surg 75: 264PubMedGoogle Scholar
  17. 17.
    Brundin P, Strecker RE, Widner H, Clarke DJ, Nilsson OG, Stedt B, Lindvall O, Björklund A (1988) Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release. Exp Brain Res 70: 192–208PubMedGoogle Scholar
  18. 18.
    Brundin P, Widner H, Rehncrona S, Björklund A, Lindvall O (1989) Influence of the size of the implantation instrument on the survival of dissociated fetal neural grafts. IIIrd International symposium on neural transplantation. Restor Neurol Neurosci [Suppl] 1: P200Google Scholar
  19. 19.
    Calne DB (1994) Neurodegenerative diseases. Saunders, PhiladelphiaGoogle Scholar
  20. 20.
    Clarke DJ, Brundin P, Nilsson OG, Strecker RE, Björklund A, Lindvall O (1988a) Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry. Exp Brain Res 73: 115–126PubMedGoogle Scholar
  21. 21.
    Clarke DJ, Dunnett SB, Isacson O, Sirinathsinghji DJS, Björklund A (1988b) Striatal grafts in rats with unilateral neostriatal lesions: ultrastructural evidence of afferent synaptic inputs from the host nigrostriatal pathway. Neuroscience 24: 791–801PubMedGoogle Scholar
  22. 22.
    Cooper IS, Bravo GJ (1958) Anterior choroidal artery occlusion, chemopallidectomy and chemothalamectomy in Parkinsonism: a consecutive seris of 700 operations. In: Fields WS (ed) Pathogenesis and treatment of Parkinsonism. Thomas, Springfield, pp 325–352Google Scholar
  23. 23.
    Coyle JT, Schwartz R (1983) The use of excitatory amino acids as selective neurotoxins. In: Björklund A, Hökfält T (eds) Handbook of chemical neuroanatomy. Elsevier, Amsterdam, pp 508–527Google Scholar
  24. 24.
    Dohan FC, Robertson JT, Feier C, Schweitzer J, Hall C, Roberson JH (1988) Autopsy findings in a Parkinson’s disease patient treated with adrenal medullary to caudate nucleus transplant. Soc Neurosci Abstr 7(4): 8Google Scholar
  25. 25.
    Duncan ID, Paino C, Archer DR, Wood PM (1992) Functional capacities of transplanted cell-sorted adult oligodendrocytes. Dev Neurosci 14: 114–122PubMedGoogle Scholar
  26. 26.
    Dunnett SB (1990) Functional analysis of neural grafts in the neostriatum. In: Björklund A, Aguayo AJ, Ottosson O (eds) Brain repair. Wenner-Gren International Symposium Series, vol 56. McMillan, London, pp 355–373Google Scholar
  27. 27.
    Dunnett SB, Annett LE (1991) Nigral transplants in primate models of parkinsonism. In: Lindvall O, Björklund A, Widner H (eds) Intracerebral transplantation in movement disorders, experimental basis and clinical experience. Elsevier, Amsterdam, pp 27–51Google Scholar
  28. 28.
    Dunnett SB, Svendsen CN (1993) Huntington’s disease: animal models and transplantation repair. Curr Opin Neurobiol 3: 790–796PubMedGoogle Scholar
  29. 29.
    Dunnett SB, Bjöklund A (eds) (1994) Functional neural transplantation. Advances in neuroscience, vol 2. Raven, New YorkGoogle Scholar
  30. 30.
    Fazzini E, Dwork AJ, Blum C, Burke R, Cote L, Goodman RR, Jacobs TP, Naini AB, Pezzoli G, Pullman S, Solomon RA, Truong D, Weber JC, Fahn S (1991) Stereotaxic implantation of autologuos adrenal medulla into caudate nucleus in four patients with Parkinsonism. Arch Neurol 48: 813–820PubMedGoogle Scholar
  31. 31.
    Fearnley J, Lees A (1994) Pathology of Parkinson’s disease. In: Calne DB (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 545–554Google Scholar
  32. 32.
    Fisher LJ, Jinnah HA, Kale LC, Higgins GA, Gage FH (1991) Survival and function of intrastriatally grafted primary fibroblasts genetically modified to produce L-dopa. Neuron 6: 371–380PubMedGoogle Scholar
  33. 33.
    Forno LS, Langsten JW (1991) Unfavorable outcome of adrenal medullary transplant for Parkinson’s disease. Acta Neuropathol 81: 691–694PubMedGoogle Scholar
  34. 34.
    Francis PT, Palmer AM, Sims NR, Bowen DM, Davison AN, Esiri MM, Neary D, Snowden JS, Wilcock GK (1985) Neurochemical studies of early-onset Alzheimer’s disease. Possible influence on treatment. N Engl J Med 313:7–11PubMedGoogle Scholar
  35. 35.
    Frank F, Sturiale C, Gaist G, Manetto V (1988) Letter to the editor: adrenal medullary autograft in human brain for Parkinson’s disease. Acta Neurochir (Wien) 94: 162–163Google Scholar
  36. 36.
    Freed W, Morihisa J, Spoor E, Hoffer B, Olson L, Seiger Å, Wyatt R (1981) Transplanted adrenal chromaffin cells in rat brain reduce lesion-induced rotational behaviour. Nature 292: 351–352PubMedGoogle Scholar
  37. 37.
    Freed WJ, Cannon-Spoor HE, Krauthamer E (1986) Intrastriatal adrenal medulla grafts in rats: long-term survival and behavioral effects. J Neurosurg 65: 664–670PubMedGoogle Scholar
  38. 38.
    Freed CR, Breeze RE, Rosenberg NL, Schneck SA, Wells TH, Barrett JN, Grafton ST, Huang SC, Eidelberg D, Rottenberg DA (1990) Transplantation of human fetal dopamine cells for Parkinson’s disease. Arch Neurol 47: 505–5PubMedGoogle Scholar
  39. 39.
    Freed CR, Breeze RE, Rosenberg NL, Schneck SA, Kriek A, Qi Jx, Lone T, Zhang Yb, Snyder JA, Wells TH, Ramig LO, Thompson L, Maziotta JC, Huang SC, Grafton ST, Brooks D, Sawle G, Schroter G, Ansari AA (1992) Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson’s disease. N Engl J Med 327: 1549–1555PubMedGoogle Scholar
  40. 40.
    Freeman TB, Hauser R, Sanberg P, Snow B, Vingerhoets JG, Olanow CW (1994) Fetal transplantation in Parkinson’s disease. Neurology 44[Suppl 2]: 324 (Abstract 783S)Google Scholar
  41. 41.
    Freeman TB, Sanberg PR, Nauert GM, Boss BD, Spector D, Olanow CW, Kordower JH (1995) The influence of donor age on the survival of solid and suspension intraparenchymal human embryonic nigral grafts. Cell Transpl 4: 141–154Google Scholar
  42. 42.
    Freund TF, Bolam JP, Björklund A, Stenevi U, Dunnett SB, Powell JF, Smith AD (1985) Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: a tyrosine hydroxylase immunocytochemical study. J Neurosci 5: 603–616PubMedGoogle Scholar
  43. 43.
    Frodl EM, Duan W-M, Sauer H, Kupsch A, Brundin P (1994) Human embryonic dopamine neurons xenografted to the rat: effects of cryopreservation and varying regional source of donor cells on transplant survival, morphology and function. Brain Res 647: 286–298PubMedGoogle Scholar
  44. 44.
    Gage FH, Friedmann T, Fisher LJ, Jinnah HA (1991) Genetically modified cells: potential therapeutic application to Parkinson’s disease. In: Lindvall O, Björklund A, Widner H (eds) Intracerebral transplantation in movement disorders. Elsevier, Amsterdam, pp 259–266Google Scholar
  45. 45.
    Gaspar P, Gray F (1984) Dementia in idiopathic Parkinson’s disease. Acta Neuropathol 64: 43–52PubMedGoogle Scholar
  46. 46.
    Goetz CG, Olanow CW, Koller WC, Penn RD, Cahili D, Morantz R, Stebbins G, Tanner CM, Klawans HL, Shannon KM, Cornelia CL, Witt T, Cox C, Waxman M, Gauger L (1989) Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in Patients with advanced Parkinson’s disease. N Engl J Med 320: 337–341PubMedGoogle Scholar
  47. 47.
    Goetz CG, Tanner CM, Penn RD, Stebbins III, Gilley DW, Shannopn KM, Klawans HL, Cornelia CM, Wilson RS, Witt T (1990) Adrenal medullary transplant to the striatum of patients with advanced Parkinson’s disease: 1-year motor and psychomotor data. Neurology 40: 237–276Google Scholar
  48. 48.
    Goetz CG, Stebbins III, Klawans HL, Koller WC, Grossman RG, Bakay RAE, Penn RD (1991) United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants: Presurgical, and 1-and 2-year follow up. Neurology 41: 1719–1722PubMedGoogle Scholar
  49. 49.
    Grabowski M, Brundin P, Johansson BB (1992) Fetal neocortical grafts implanted in adult hypertensive rats with cortical infacts following a middle cerebral artery occlusion: Ingrowth of afferent fibers from the host brain. Exp Neural 116: 105–121Google Scholar
  50. 50.
    Grabowski M, Johansson BB, Brundin P (1995) Neocortical grafts placed in the infarcted brain of adult rats: few or no efferent fibers grow from transplant to host. Exp Neural 134: 273–276Google Scholar
  51. 51.
    Guttman M, Burns RS, Martin WRW, Peppard RF, Adam MJ, Ruth TJ, Allen G, Parker RA, Tulipan, Calne DB (1989) PET studies of Parkin-sonian patients treated wit autologous adrenal implants. Can J Sci 16: 305–309Google Scholar
  52. 52.
    Hadani M, Freeman T, Pearson J, Young W, Flamm E (1987) Embryonic cortical transplants survive in middle cerebral artery territory after permanent arterial occlusion in adult rats. Ann NY Acad Sci 495: 711–714Google Scholar
  53. 53.
    Hefti F, Schneider LS (1991) Nerve growthfactor and Alzheimer’s disease. Clin Neuropharmacol 14 [Suppl]: S62–S76PubMedGoogle Scholar
  54. 54.
    Henderson BTH, Clough CG, Hughes RC, Hitchcock ER, Kenny BG (1991) Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson’s disease. Arch Neurol 48: 822–827PubMedGoogle Scholar
  55. 55.
    Hirsch EC, Duyckaerts C, Javoy-Agid F, Hauw J-J, Agid Y (1990) Does adrenal graft enhance recovery of dopaminergic neurons in Parkinson’s disease? Ann Neurol 27: 676–682PubMedGoogle Scholar
  56. 56.
    Hitchcock ER, Henderson BTH, Kenny BG, Clough CG, Hughes RC, Detta A (1991) Stereotactic implantation of foetal mesencephalon. In: Lindvall O, Björklund A, Widner H (eds) Intracerebral transplantation in movement disorders. Elsevier, Amsterdam, pp 79–86Google Scholar
  57. 57.
    Horellou P, Brundin P, Kalén P, Mallet J, Björklund A (1990a) In vivo release of DOPA and dopamine from genetically engineered cells grafted to the denervated striatum. Neuron 5: 393–402PubMedGoogle Scholar
  58. 58.
    Horellou P, Marlier L, Privat A, Mallet J (1990b) Behavioral effect of engineered cells that synthesize L-dopa or dopamine after grafting into the rat neostriatum. Eur J Neurosci 2: 116–119PubMedGoogle Scholar
  59. 59.
    Hurtig H, Joyce J, Slafek JR, Trojanowski JQ (1989) Postmortem analysis of adrenal-medulla-to-caudate autograft in a patient with Parkinson’s disease. Ann Neurol 25: 607–616PubMedGoogle Scholar
  60. 60.
    Itakura T, Kamei I, Nakai K, Naka Y, Nakakita K, Imay H, Komai N (1988) Autotransplantation of the superior cervical ganglion into the brain, a possible therapy for Parkinson’s disease. J Neurosurg 68: 955–959PubMedGoogle Scholar
  61. 61.
    Jankovic J, Grossman R, Goodman C, Pirizzolo F, Schneider L, Zhu Z, Scardino P, Garber AJ, Jhingran SG, Martin S (1989) Clinical, biochemical, and neuropathologic findings following transplantation of adrenal medulla to the caudate nucleus for treatment of Parkinson’s disease. Neurology 39: 1227–1234PubMedGoogle Scholar
  62. 62.
    Jacques D, Kopyov OV, Markham CH, Rand RW, Snow B, Vingerhoets F, Lieberman A (1994) One-year follow-up of six Parkinson’s patients with fetal ventral mesencephalon grafts. Neurology 44[Suppl 2]: A223 (Abstract 780S)Google Scholar
  63. 63.
    Jellinger K (1987a) Neuropathological substrates of Alzheimer’s disease and Parkinson’s disease. J Neural Transm [Suppl] 24: 109–129Google Scholar
  64. 64.
    Jellinger K (1987b) Quantitative changes in some subcortical nuclei in aging, Alzheimer’s disease and Parkinson’s disease. Neurobiol Aging 8: 556–561PubMedGoogle Scholar
  65. 65.
    Jiao S, Ding Y, Zhang W, Cao J, Zhang G, Zhang Z, Ding M, Zhang Z, Meng J (1989) Adrenal medullary autografts in patients with Parkinson’s disease. N Eng J Med 321: 324–325Google Scholar
  66. 66.
    Jiao S, Gurevich V, Wolff (1993) Long-term correction of rat model of Parkinson’s disease by gene therapy. Nature 362: 450–453PubMedGoogle Scholar
  67. 67.
    Katzman R (1986) Alzheimer’s disease. N Engl J Med 314: 964–973PubMedGoogle Scholar
  68. 68.
    Kawaja MD, Fagan AM, Firestein BL, Gage FH (1991) Intracerebral grafting of cultured autologous skin fibroblasts into the rat striatum: an assessment of graft size and ultrastructure. J Comp Neurol 308: 2–13Google Scholar
  69. 69.
    Kelly PJ, Ahlskog JE, van Heerden JA, Carmichael SW, Stoddard SL, Bell GN (1989) Adrenal medullary autograft transplantation into the striatum of patients with Parkinson’s disease. Mayo Clin Proc 64: 282–290PubMedGoogle Scholar
  70. 70.
    Kesslak JP, Nieto-Sampedro M, Globus J, Cotman CW (1986) Transplants of purified astrocytes promote behavioral recovery after frontal cortex ablation. Exp Neurol 92: 377–390PubMedGoogle Scholar
  71. 71.
    Kolarik J, Nadvornic P, Rozhold O (1990) Transplantation of embryonal nerve tissue into the brain under experimental and clinical conditions. Rozhl Chir 69(9): 569–574PubMedGoogle Scholar
  72. 72.
    Kordower JH, Freeman TB, Snow BJ, Vingerhoets FJG, Mufson EJ, Sanberg PR, Hauser RA, Smith DA, Nauert GM, Pearl DP, Olanow CW (1995) Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease. N Engl J Med 332: 1118–1124PubMedGoogle Scholar
  73. 73.
    Labbe R, Firl A, Mufson EJ, Stein DG (1983) Fetal brain transplants: reduction of cognitive deficits in rats with frontal cortex lesions. Science 221:470–472PubMedGoogle Scholar
  74. 74.
    Laitinen LV, Bergenheim AT, Hariz MI (1992) Leksell’s postero ventral pallidotomy in the treatment of Parkinson’s disease. J Neurosurg 76: 53–61PubMedGoogle Scholar
  75. 75.
    Lange HW, Thörner GW, Hopf A, Schröder KF (1976) Morphometric studies of the neuropathological changes in choreatic diseases. J Neurol Sci 28: 401–425PubMedGoogle Scholar
  76. 76.
    Lindvall O, Backlund E-O, Farde L, Sedvall G, Freedman R, Hoffer B, Nobin A, Seiger Å, Olson L (1987) Transplantation in Parkinson’s disease: two cases of adrenal medullary grafts to the putamen. Ann Neurol 22: 457–468PubMedGoogle Scholar
  77. 77.
    Lindvall O, Rehncrona S, Brundin P, Gustavii B, Åstedt B, Widner H, Lindholm T, Björklund A, Leenders KL, Rothwell JC, Frackowiak R, Marsden CD, Johnels B, Steg G, Freedman R, Hoffer BJ, Seiger Å, Bygdeman M, Strömberg I, Olson L (1989) Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease. Arch Neurol 46: 615–631PubMedGoogle Scholar
  78. 78.
    Lindvall O, Brundin P, Widner H, Rehncrona S, Gustavii B, Frackowiak R, Leenders KL, Sawle G, Rothwell JC, Marsden CD, Björklund A (1990) Grafts of fetaldopamine neurons survive and improve motor function in Parkinson’s disease. Science 247: 574–577PubMedGoogle Scholar
  79. 79.
    Lindvall O, Widner H, Rehncrona S, Brundin P, Odin P, Gustavii B, Frackowiak R, Leenders KL, Sawle G, Rothwell JC, Björklund A, Marsden CD (1992) Transplantation of fetal dopamine neurons in Parkinson’s disease: one year clinical neurophysiological observations in two patients with putaminal implants. Ann Neurol 31: 155–165PubMedGoogle Scholar
  80. 80.
    Lindvall O, Sawle G, Widner H, Rothwell JC, Björklund A, Brooks D, Brundin P, Frackowiak R, Marsden CD, Odin P, Rehncrona S (1994a) Evidence for long term survival and function of dopaminergic grafts in progressive Parkinson’s disease. Ann Neurol 35: 172–180PubMedGoogle Scholar
  81. 81.
    Lindvall O (1994b) Neural transplantation in Parkinson’s disease. In: Dunnett SB, Björklund A (eds) Functional neural transplantation. Raven, New York, pp 103–137Google Scholar
  82. 82.
    López-Lozano JJ, Bravo G, Brera B, Uría J, Dargallo J, Salmean J, Insausti J, Cerrolaza J (1991) Can an analogy be drawn between the clinical evolution of Parkinson’s patients who undergo autoimplantation of adrenal medulla and those of fetal ventral mesencphalon transplant recipients? In: Lindvall O, Björklund A, Widner H (eds) Intracerebral transplantation in movement disorders; experimental basis and clinical experience. Elsevier, Amsterdam, pp 87–98Google Scholar
  83. 83.
    López-Lozano JJ, Bravo G, Abascal J (1991) Grafting of perfused adrenal medullary tissue into the caudate nucleus of patients with Parkinson’s disease. J Neurosurg 75: 234–243PubMedGoogle Scholar
  84. 84.
    López-Lozano JJ, Bravo G, Abascal J, Brera B, Santos H, Gomez-Angulo C (1992) Co-transplantation of peripheral nerve and adrenal medulla in Parkinson’s disease. Lancet 339: 430PubMedGoogle Scholar
  85. 85.
    Madrazo I, Drucker-Colin R, Diaz V, Martinez-Mata J, Torres C, Becerril JJ (1987) Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson’s disease. N Engl J Med 316: 831–834PubMedGoogle Scholar
  86. 86.
    Madrazo I, Franco-Bourland R, Aguilera M, Ostrosky-Solis F (1989) Hispanic registry of graft procedures for Parkinson’s disease. Lancet ii: 751–752Google Scholar
  87. 87.
    Madrazo I, Franco-Bourland R, Ostrosky-Solis F, Aguilera M, Cuevas C, Zamorano C, Morelos A, Magallon E, Guizar-Sahagun G (1990) Fetal homotransplants (ventral mesencephalon and adrenal tissue) to the striatum of Parkinsonian subjects. Arch Neurol 47: 1281–1285PubMedGoogle Scholar
  88. 88.
    Madrazo I, Franco-Bourland R, Ostrosky-Solis F, Aguilera M, Cuevas C, Alvarez F, Magallon E, Zamorano C, Morelos A (1990) Neural transplantation (auto-adrenal, fetal nigral and fetal adrenal) in Parkinson’s disease: the Mexican experience. In: Dunnett SB, Richards SJ (eds) Neural transplantation: from molecular basis to clinical application. Progr Brain Res 82: 593–602Google Scholar
  89. 89.
    Madrazo I, Cuevas C, Castrejon H, Guizar-Sahagun G, Franco-Bourland RE, Ostrosky-Solis F, Aguilera M, Magallon E (1993) Primer homotransplante fetal homotopico de estrediado para el tratamiento de la enfermedad de Huntington. Gac Med Max 129(2): 109–117Google Scholar
  90. 90.
    Mahalik TJ, Finger TE, Stömberg I, Olson L (1985) Substantia nigra transplants into the denervated striatum of the rat: ultrastructure of graft and host interactions. J Comp Neurol 240: 60–70PubMedGoogle Scholar
  91. 91.
    Mampalam TJ, Gonzales MF, Weistein P, Sharp FR (1988) Neuronal changes in fetal cortex transplanted to ischemic adult rat cortex. J Neurosurg 69: 904–912PubMedGoogle Scholar
  92. 92.
    Mayer E, Fawcett JW, Dunnett SB (1993) Basic fibroblast growth factor promotes the survival of embryonic ventral mesencephalic dopaminergic neurons-II. Effects on nigral transplants in vivo. Neuroscience 56: 389–398Google Scholar
  93. 93.
    Meyers R (1942) The modification of alternating tremor, rigidity and festina-tion by surgery of the basal ganglia. Res Publ Assoc Nerv Ment Dis 21: 602–655Google Scholar
  94. 94.
    Molina H, Quinones R, Alvarez L, Galarraga J, Piedra Suárez C, Rachid M, García JC, Perry TL, Santana A, Carménate H, Macías R, Torres O, Rojas MJ, Córdova F, Munos JL (1991) Transplantation of human fetal mesencephalic tissue in caudate nucleus as treatment for Parkinson’s disease: the cuban experience. In: Linvall O, Björklund A, Widner H (eds) Intracerebral transplantation in movement disorders. Experimental basis and clinical experiences. Elsevier, Amsterdam, pp 99–110Google Scholar
  95. 95.
    Morihisa JM, Nakamura RK, Freed Wj (1987) Transplantation techniques and the survival of adrenal medulla autografts in the primate brain. Ann NY Acad Sci 495: 599–605PubMedGoogle Scholar
  96. 96.
    Nakai M, Itakura T, Kamei I, Nakai K, Naka Y, Imai H, Komai N (1990) Autologous transplantation of the superior cervical gangleon into the brain of parkinsonian monkeys. J Neurosurg 72: 91–95PubMedGoogle Scholar
  97. 97.
    Nakao N, Frodl EM, Duan W-M, Widner H, Brundin P (1994) Lazaroids improve the survival of grafted rat embryonic dopamine neurons. Proc Natl Acad Sci USA 91: 12408–12414PubMedGoogle Scholar
  98. 98.
    Narabayashi H, Okuma, T, Shikiba S (1956) Procaine-oil blocking of the globus pallidus. Arch Neurol 75: 36–48Google Scholar
  99. 99.
    Nikkhah G, Cunningham MG, Jödicke A, Björklund A (1994) Improved graft survival and striatal reinnervation by microtransplantation of fetal nigral cell suspensions in the rat Parkinson model. Brain Res 633: 133–143PubMedGoogle Scholar
  100. 100.
    Nyberg P, Nordberg A, Wester P, Winblad B (1983) Dopaminergic deficiency is more pronounced in putamen than in nucleus caudatus in Parkinson’s disease. Neurochem Pathol 1: 193–202Google Scholar
  101. 101.
    Olanow CW, Koller W, Goetz CG, Stebbins GT, Cahili DW, Gauger LL, Morantz R, Penn RD, Tanner CM, Klawans HL, Shannon HM, Cornelia CL, Witt T (1990) Autologous transplantation of adrenal medulla in Parkinson’s disease; 18-month results. Arch Neurol 47: 1286–1289PubMedGoogle Scholar
  102. 102.
    Olson L (1970) Fluoroscence histochemical evidence for axonal growth and secretion from transplanted adrenal medullary tissue. Histochemie 22: 1–7PubMedGoogle Scholar
  103. 103.
    Olson L, Seiger Å, Freedman R, Hoffer B (1980) Chromaffin cells can innervate brain tissue: evidence from intraocular double grafts. Exp Neurol 70: 414–426PubMedGoogle Scholar
  104. 104.
    Olson L, Backlund E-O, Ebendal T, Freedman R, Hamberger B, Hansson P, Hoffer B, Lindblom U, Meyerson B, Strömberg I, Sydow O, Seiger Å (1991) Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson’s disease; one year follow up of first clinical trial. Arch Neurol 48: 373–381PubMedGoogle Scholar
  105. 105.
    Olson L (1993) NGF and the treatment of Alzheimer’s disease. Exp Neurol 124: 5–15PubMedGoogle Scholar
  106. 106.
    Penn RD, Goetz CG, Tanner CH, Klawans HL, Shannon KM, Cornelia CL, Witt TR (1988) The adrenal medulla transplant operation for Parkinson’s disease: clinical observations in five patients. Neurosurgery 22: 999–1004PubMedGoogle Scholar
  107. 107.
    Perlow MJ, Freed WJ, Hoffer BJ, Seiger Å, Olson L, Wyatt RJ (1979) Brain grafts reduce motor abnormalities produced by destruction of the nigrostriatal dopamine system. Science 204: 643–647PubMedGoogle Scholar
  108. 108.
    Peschanski M, Defer G, N’Guyen JP, Ricolfi F, Monfort JC, Remy P, Geny C, Samson Y, Hantraye P, Jeny R, Gaston A, Kéravel Y, Degos JD, Cesaro P (1994) Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson’s disease following intrastriatal transplantation of foetal ventral mesencephalon. Brain 117: 487–499PubMedGoogle Scholar
  109. 109.
    Peterson DI, Price ML, Small C (1989) Autopsy findings in a patient who had an adrenal-to-brain transplant for Parkinson’s disease. Neurology 39: 235–238PubMedGoogle Scholar
  110. 110.
    Pezzoli G, Motti E, Zecchenelli A, Ferrante C, Silani V, Falini A, Pizzuti A, Mulazzio D, Baratta P, Vegeto A, Villani R, Scarlato G (1990) Adrenal medulla autograft in 3 parkinsonian patients: results using two different approaches. In: Dunnett SB, Richards S-J (eds) Neural transplantation: from molecular basis to clinical application. Progr Brain Res 82: 677–682Google Scholar
  111. 111.
    Plunkett RJ, Bankiewicz KS, Cummins AC, Miletich RS, Schwartz JP, Oldfield EH (1990) Long-term evaluation of hemiparkinsonian monkeys after adrenal autografting or cavitation alone. J Neurosurg 73: 918–926PubMedGoogle Scholar
  112. 112.
    Redmond Jr DE, Leranth C, Spencer DD, Robbins R, Vollmer T, Kim JH, Roth RH (1990) Fetal neural graft survival. Lancet 336: 820–82PubMedGoogle Scholar
  113. 113.
    Sauer H, Brundin P (1991) Effects of cool storage on survival and function of intrastriatal ventral mesencephalic grafts. Restor Neurol Sci 2: 123–135Google Scholar
  114. 114.
    Seiger A, Nordberg A, von Holst H, Bäckman L, Ebendal T, Alafuzoff I, Amberla K, Hartvig P, Herlitz A, Lilja A et al (1993) Intracranial infusion of purified nerve growth factor to an Alzheimer patient: the first attempt of a possible future treatment strategy. Behav Brain Res 57: 255–261PubMedGoogle Scholar
  115. 115.
    Snow BJ, Vingerhoets FJG, Schulzer M, Calne DB (1994) Fluorodopa PET evolution of bilateral striatal fetal mesencephalic graft for idiopathic Parkinsonism. Neurology 44[Suppl 2]: A281 (Abtract 609P)Google Scholar
  116. 116.
    Spencer DD, Robbins RJ, Naftolin F, Marek KL, Vollmer T, Leranth C, Roth RH, Price LH, Gjedde A, Bunney BS, Sass KJ, Elsworth JD, Kier EL, Makuch R, Hoffer PB, Redmond ER (1992) Unilateral transplantation of human fetal mesecephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N Engl J Med 327: 1541–1548PubMedGoogle Scholar
  117. 117.
    Sramka M, Rattaj M, Molina H, Vojtassak J, Belan V, Ruzicky E (1992) Stereotactic technique and patophysiological mechnisms of neurotransplantation in Huntington’ s chorea. Stereotactic Funct Neurosurg 58: 79–83Google Scholar
  118. 118.
    Starkova L, Mrna B, Bartosova S (1993) Neurotransplantation—a new method of treatment in psychiatry? Acta Univ Palacki Olomuc Fac Med 136: 33–35PubMedGoogle Scholar
  119. 119.
    Strecker RE, Sharp T, Brundin P, Zetterström T, Ungerstedt U, Björklund A (1987) Autoregulation of dopamine release and metabolism by intrastriatal nigral grafts as revealed by intracerebral dialysis. Neuroscience 22: 169–178PubMedGoogle Scholar
  120. 120.
    Strömberg I, Herrera-Marschitz M, Hultgren L, Ungerstedt U, Olson L (1984) Adrenal medullary implants in the dopamine-denervated rat striatum. 1. Acute catecholamine levels in grafts and host caudate as determined by HPLC-electrochemistry and fluorescence histochemical image analysis. Brain Res 297: 41–51PubMedGoogle Scholar
  121. 121.
    Strömberg I, Herrera-Marschitz M, Ungerstedta U, Ebendal T, Olson L (1985) Chronic implants of chromaffin tissue into the dopamine-denervated striatum. Effects of NGF on graft survival, fiber outgrowth and rotational behavior. Exp Brain Res 60: 335–349PubMedGoogle Scholar
  122. 122.
    Svennilson E, Torvik A, Lowe R, Leksell L (1960) Treatment of parkinsonism by stereotactic thermolesions in the pallidal region. Acta Psychiatr Scand 35: 358–377PubMedGoogle Scholar
  123. 123.
    Takeuchi J, Takebe Y, Sakakura T, Hara Y, Yasuda T, Imai T (1990) Adrenal medulla transplantation into the putamen in Parkinson’s disease. Neurosurgery 26: 499–503PubMedGoogle Scholar
  124. 124.
    Tontsch U, Archer DR, Dubois-Dalcq M, Duncan ID (1994) Transplantation of an oligodendrocyte cell line leading to extensive myelination. Proc Natl Acad Sci 91(24): 11616–11620PubMedGoogle Scholar
  125. 125.
    Tönder N, Sörensen T, Zimmer J, Jörgensen MB, Johansen FF, Diemer NH (1989) Neural grafting to ischemic lesions of the adult rat hippocampus. Exp Brain Res 74: 512–526PubMedGoogle Scholar
  126. 126.
    Utzschneider DA, Archer DR, Kocsis JD, Waxman SG, Duncan ID (1994) Transplantation of glial cells enhances action potential conduction of amyelinated spinalcord axons in the myelin-deficient rat. Proc Natl Acad Sci 91(1): 53–57PubMedGoogle Scholar
  127. 127.
    Waters C, Itabashi HH, Apuzzo LJ, Weiner LP (1990) Adrenal to caudate transplantation—postmortem study. Mov Disord 5: 248–250PubMedGoogle Scholar
  128. 128.
    Wictorin K, Simerly RB, Isacson O, Swanson LW, Björklund A (1989) Connectivity of striatal grafts implanted into the ibotenic acid-lesioned striatum-III. Efferent projecting graft neurons and their relation to host afférents within the grafts. Neuroscience 30; 313–330PubMedGoogle Scholar
  129. 129.
    Widner H, Tetrud J, Rehncrona S, Snow B, Brundin P, Gustavii B, Björklund A, Lindvall O, Langston W (1992) Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP). N Engl J Med 327: 1556–1563PubMedGoogle Scholar
  130. 130.
    Widner H, Tetrud J, Rehncrona S, Snow B, Brundin P, Björklund A, Lindvall O, Langston JW (1993) Fifteen month’s follow up on bilateral embryonic meseneephalic grafts in two cases of severe MPTP-induced parkinsonism. Adv Neurol 60: 729–733PubMedGoogle Scholar
  131. 131.
    Yamamoto T, Hirano A (1985) Nucleus raphe dorsalis in Alzheimer’s disease: neurofibrillary tangles and loss of large neurons. Ann Neurol 17: 357–361Google Scholar
  132. 132.
    Zabek M, Mazurowski W, Dymecki J, Stelmachów J, Zawada E (1994) A long term follow-up of fetal dopaminergic neurons transplantation into the brain of three parkinsonian patients. Restorative Neurol Neurosci 6: 97–106Google Scholar
  133. 133.
    Zetterström T, Brundin P, Gage FH, Sharp T, Isacson O, Dunnett SB, Ungerstedt U, Björklund A (1986) In vivo measurement of spontaneous release and metabolism of dopamine from intrastriatal nigral grafts using intracerebral dialysis. Brain Res 362: 344–349PubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 1997

Authors and Affiliations

  • S. Rehncrona
    • 1
  1. 1.Department of NeurosurgeryUniversity Hospital of LundLundSweden

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