Cell Transplantation for the Treatment of Parkinson's Disease

Thyagarajan Subramanian

doi:10.1055/s-2001-13125

Seminars in Neurology, Inhaltsverzeichnis

Semin Neurol 2001; 21(1): 103-116
DOI: 10.1055/s-2001-13125

Cell Transplantation for the Treatment of Parkinson's Disease

Thyagarajan Subramanian

Department of Neurology, Cleveland Clinic Foundation, Cleveland, Ohio

Abstract

ABSTRACT

Cell transplantation is an experimental therapy for Parkinson's disease (PD) and other movement disorders. Several open-label research trials have shown clinically meaningful improvement in parkinsonian signs and symptoms after striatal transplantation of allogeneic fetal ventral mesencephalic (FVM) tissue. However, ethical concerns, variability in surgical techniques, and reports of unusual late complications in a few patients in a clinical trial have limited the use of allogeneic FVM tissue to a few research centers. Research into alternative cell sources such as porcine FVM and allogeneic retinal pigment epithelial cells has shown promising results in preclinical trials, and they are currently being tested in clinical trials. Novel strategies to improve cell survival and to avoid immune rejection of transplants show promising results in preclinical trials. This article focuses on these recent advances and compares the potential clinical utility of these emerging cell therapies for the treatment of advanced PD.

KEYWORD

Brain - central nervous system - clinical trials - animal models - neural transplantation - MPTP

Volltext

Referenzen

REFERENCES

1 Chase T N, Engber T M, Mouradian M M. Palliative and prophylactic benefits of continuously administered dopaminomimetics in Parkinson's disease. Neurology . 1994; S15-S18 (S15-S18)
2 Chase T N, Juncos J, Serrati C, Fabbrini G, Bruno G. Fluctuation in response to chronic levodopa therapy: pathogenetic and therapeutic considerations. Adv Neurol . 1987; 45 477-480
3 Fabbrini G, Juncos J, Mouradian M M, Serrati C, Chase T N. Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease. Ann Neurol . 1987; 21 370-376
4 Marsden C D. Problems with long-term levodopa therapy for Parkinson's disease. Clin Neuropharmacol . 1994; S32-S44 (S32-S44)
5 Backlund E O, Granberg B, Hamberger E. Transplantation of adrenal medullary tissue to striatum in parkinsonism: first trials. J Neurosurg . 1985; 62 169-173
6 Lindvall O. Neural transplantation: a hope for patients with Parkinson's disease. Neuroreport . 1997; 8 iii-x
7 Watts R L, Subramanian T, Freeman A. Effect of stereotaxic intrastriatal cografts of autologous adrenal medulla and peripheral nerve in Parkinson's disease: two-year follow-up study. Exp Neurol . 1997; 147 510-517
8 Subramanian T, Emerich D F, Bakay R A. Polymer-encapsulated PC-12 cells demonstrate high-affinity uptake of dopamine in vitro and ¹⁸F-dopa uptake and metabolism after intracerebral implantation in nonhuman primates. Cell Transplant . 1997; 6 469-477
9 Aebischer P, Tresco P A, Sagen J, Winn S R. Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats. Brain Res . 1991; 560 43-49
10 Aebischer P, Tresco P A, Winn S R, Greene L A, Jaeger C B. Long-term cross-species brain transplantation of a polymer-encapsulated dopamine-secreting cell line. Exp Neurol . 1991; 111 269-275
11 Diamond S G, Markham C H, Rand R W, Becker D P, Treciokas L J. Four-year follow-up of adrenal-to-brain transplants in Parkinson's disease. Arch Neurol . 1994; 51 559-563
12 Freed W J, Poltorak M, Becker J B. Intracerebral adrenal medulla grafts: a review. Exp Neurol . 1990; 110 139-166
13 Itakura T, Nakai M, Nakao N. Transplantation of autologous cervical sympathetic ganglion into the brain with Parkinson's disease: experimental and clinical studies. Cell Transplant . 1994; S43-S45 (S43-S45)
14 Madrazo I, Franco B R, Aguilera M. Autologous adrenal medullary, fetal mesencephalic, and fetal adrenal brain transplantation in Parkinson's disease: a long-term postoperative follow-up. J Neural Transplant Plast . 1991; 2 157-164
15 Manaster J S, Feuerman T, Reynolds C P, Markham C H. Transplantation of human neuroblastoma cells, catecholaminergic and non-catecholaminergic: effects on rotational behavior in Parkinson's rat model. J Neural Transplant Plast . 1992; 3 139-150
16 Rohrer D C, Nilaver G, Nipper V, Machida C A. Genetically modified PC12 brain grafts: survivability and inducible nerve growth factor expression. Cell Transplant . 1996; 5 57-68
17 Deacon T, Schumacher J, Dinsmore J. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease. Nature Medicine . 1997; 3 350-353
18 Isacson O, Deacon T W, Pakzaban P. Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres. Nat Med . 1995; 1 1189-1194
19 Sanberg P R, Borlongan C V, Othberg A I. Testis-derived Sertoli cells have a trophic effect on dopamine neurons and alleviate hemiparkinsonism in rats. Nat Med . 1997; 3 1129-1132
20 Svendsen C N, Caldwell M A, Shen J. Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's disease. Exp Neurol . 1997; 148 135-146
21 Tornatore C, Baker-Cairns B, Yadid G. Expression of tyrosine hydroxylase in an immortalized human fetal astrocyte cell line: in vitro characterization and engraftment into the rodent striatum. Cell Transplant . 1996; 5 145-163
22 Yong V W, Guttman M, Kim S U. Transplantation of human sympathetic neurons and adrenal chromaffin cells into parkinsonian monkeys: no reversal of clinical symptoms. J Neurol Sci . 1989; 94 51-67
23 Subramanian T, Burnette B, Miller G W. Characterization of the dopaminergic properties of human retinal pigmented epithelial (hRPE) cells and the effect of intrastriatal transplantation of hRPE cells in hemiparkinsonian (HP) monkeys. In: 5th International Congress of Parkinson's Disease and Movement Disorders, New York, 1998
24 Mendez I, Hong M. Reconstruction of the striato-nigro-striatal circuitry by simultaneous double dopaminergic grafts: a tracer study using fluorogold and horseradish peroxidase. Brain Res . 1997; 778 194-205
25 Starr P A, Wichmann T, van Horne C, Bakay R A. Intranigral transplantation of fetal substantia nigra allograft in the hemiparkinsonian rhesus monkey. Cell Transplant . 1999; 8 37-45
26 Bjorklund A, Lindvall O. Cell replacement therapies for central nervous system disorders. Nat Neurosci . 2000; 3 537-544
27 Drucker-Colin R, Verdugo-Diaz L, Morgado-Valle C. Transplant of cultured neuron-like differentiated chromaffin cells in a Parkinson's disease patient. A preliminary report. Arch Med Res . 1999; 30 33-39
28 Yoshida H, Date I, Shingo T. Evaluation of reaction of primate brain to grafted PC12 cells. Cell Transplant . 1999; 8 427-430
29 Mendez I, Baker K A, Hong M. Simultaneous intrastriatal and intranigral grafting (double grafts) in the rat model of Parkinson's disease. Brain Res Brain Res Rev . 2000; 32 328-339
30 Huffaker T K, Boss B D, Morgan A S. Xenografting of fetal pig ventral mesencephalon corrects motor asymmetry in the rat model of Parkinson's disease. Exp Brain Res . 1989; 77 329-336
31 Horvath M, Pasztor E, Palkovits M. Autotransplantation of superior cervical ganglion to the caudate nucleus in three patients with Parkinson's disease (preliminary report). Neurosurg Rev . 1990; 13 119-122
32 Horellou P, Lundberg C, Le Bourdelles B. Behavioural effects of genetically engineered cells releasing dopa and dopamine after intracerebral grafting in a rat model of Parkinson's disease. J Physiol . 1991; 85 158-170
33 Schueler S B, Ortega J D, Sagen J, Kordower J H. Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability. J Neurosci . 1993; 13 4496-4510
34 Ishida A, Mukawa J. [L-DOPA-producing primary fibroblasts genetically modified with a retrovirus vector system]. No To Shinkei Brain Nerve . 1995; 47 887-892
35 Meyer C H, Detta A, Kudoh C. Hitchcock's experimental series of foetal implants for Parkinson's disease: co-grafting ventral mesencephalon and striatum. Acta Neurochir Suppl . 1995; 64 1-4
36 Bencsics C, Wachtel S R, Milstien S. Double transduction with GTP cyclohydrolase I and tyrosine hydroxylase is necessary for spontaneous synthesis of L-DOPA by primary fibroblasts. J Neurosci . 1996; 16 4449-4456
37 Kaddis F G, Clarkson E D, Bell K P, Choi P K, Freed C R. Co-grafts of muscle cells and mesencephalic tissue into hemiparkinsonian rats: behavioral and histochemical effects. Brain Res Bull . 2000; 51 203-211
38 Kakishita K, Elwan M A, Nakao N, Itakura T, Sakuragawa N. Human amniotic epithelial cells produce dopamine and survive after implantation into the striatum of a rat model of Parkinson's disease: a potential source of donor for transplantation therapy. Exp Neurol . 2000; 165 27-34
39 Zawada W M, Cibelli J B, Choi P K. Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats. Nat Med . 1998; 4 569-574
40 Freed C R, Breeze R E, Rosenberg N L. Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson's disease. N Engl J Med . 1992; 327 1549-1555
41 Hauser R A, Freeman T B, Snow B J. Long-term evaluation of bilateral fetal nigral transplantation in Parkinson disease. Arch Neurol . 1999; 56 179-187
42 Lindvall O. Update on fetal transplantation: the Swedish experience. Mov Disord . 1998; 83-87 (83-87)
43 Widner H, Tetrud J, Rehncrona S. Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). N Engl J Med . 1992; 327 1556-1563
44 Zigova T, Pencea V, Betarbet R. Neuronal progenitor cells of the neonatal subventricular zone differentiate and disperse following transplantation into the adult rat striatum. Cell Transplant . 1998; 7 137-156
45 Olanow C W, Freeman T B, Kordower J H. Neural transplantation as a therapy for Parkinson's disease. Adv Neurol . 1997; 74 249-269
46 Olanow C W, Kordower J H, Freeman T B. Fetal nigral transplantation as a therapy for Parkinson's disease. Trends Neurosci . 1996; 19 102-109
47 Tabbal S, Fahn S, Frucht S. Fetal tissue transplantation (correction of transplanation) in Parkinson's disease. Curr Opin Neurol . 1998; 11 341-349
48 Clarkson E D, Freed C R. Development of fetal neural transplantation as a treatment for Parkinson's disease. Life Sci . 1999; 65 2427-2437
49 Jacques D B, Kopyov O V, Eagle K S, Carter T, Lieberman A. Outcomes and complications of fetal tissue transplantation in Parkinson's disease. Stereotact Funct Neurosurg . 1999; 72 219-224
50 Kupsch A, Earl C. Neurosurgical interventions in the treatment of idiopathic Parkinson disease: neurostimulation and neural implantation. J Mol Med . 1999; 77 178-184
51 Lindvall O. Cerebral implantation in movement disorders: state of the art [editorial]. Mov Disord . 1999; 14 201-205
52 Lindvall O. Neural transplantation: can we improve the symptomatic relief?. Adv Neurol . 1999; 80 635-640
53 Widner H. The case for neural tissue transplantation as a treatment for Parkinson's disease. Adv Neurol . 1999; 80 641-649
54 Barker R A, Kendall A L, Widner H. Neural tissue xenotransplantation: what is needed prior to clinical trials in Parkinson's disease?. <~>Neural Tissue Xenografting Project. Cell Transplant . 2000; 9 235-246
55 Follett K A. The surgical treatment of Parkinson's disease. Annu Rev Med . 2000; 51 135-147
56 Lang A E. Surgery for Parkinson disease: a critical evaluation of the state of the art. Arch Neurol . 2000; 57 1118-1125
57 Uitti R J. Surgical treatments for Parkinson's disease. Can Fam Physician . 2000; 46 368-373
58 Piccini P, Brooks D J, Bjorklund A. Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient. Nat Neurosci . 1999; 2 1137-1140
59 Sawle G V, Bloomfield P M, Bjorklund A. Transplantation of fetal dopamine neurons in Parkinson's disease: PET [¹⁸F]6-L-fluorodopa studies in two patients with putaminal implants. Ann Neurol . 1992; 31 166-173
60 Lindvall O, Sawle G, Widner H. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease. Ann Neurol . 1994; 35 172-180
61 Wenning G K, Odin P, Morrish P. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease. Ann Neurol . 1997; 42 95-107
62 Spencer D D, Robbins R J, Naftolin F. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson's disease. N Engl J Med . 1992; 327 1541-1548
63 Lindvall O, Rehncrona S, Brundin P. Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease: a detailed account of methodology and a 6-month follow-up. Arch Neurol . 1989; 46 615-631
64 Freed C R, Breeze R E, Rosenberg N L. Transplantation of human fetal dopamine cells for Parkinson's disease: results at 1 year. Arch Neurol . 1990; 47 505-512
65 Henderson B T, Clough C G, Hughes R C, Hitchcock E R, Kenny B G. Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease. Arch Neurol . 1991; 48 822-827
66 Subrt O, Tichy M, Vladyka V, Hurt K. Grafting of fetal dopamine neurons in Parkinson's disease: the Czech experience with severe akinetic patients. Acta Neurochir Suppl (Wien) . 1991; 52 51-53
67 Hoffer B J, Leenders K L, Young D. Eighteen-month course of two patients with grafts of fetal dopamine neurons for severe Parkinson's disease. Exp Neurol . 1992; 118 243-252
68 Iacono R P, Tang Z S, Mazziotta J C, Grafton S, Hoehn M. Bilateral fetal grafts for Parkinson's disease: 22 months' results. Stereotact Funct Neurosurg . 1992; 58 84-87
69 Molina H, Quinones-Molina R, Munoz J. Neurotransplantation in Parkinson's disease: from open microsurgery to bilateral stereotactic approach: first clinical trial using microelectrode recording technique. Stereotact Funct Neurosurg . 1994; 62 204-208
70 Peschanski M, Defer G, N'Guyen J P. Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson's disease following intrastriatal transplantation of foetal ventral mesencephalon. Brain . 1994; 117 487-499
71 Freeman T B, Olanow C W, Hauser R A. Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease. Ann Neurol . 1995; 38 379-388
72 Lopez-Lozano J J, Bravo G, Brera B. Long-term follow-up in 10 Parkinson's disease patients subjected to fetal brain grafting into a cavity in the caudate nucleus: the Clinica Puerta de Hierro experience. CPH Neural Transplantation Group. Transplant Proc . 1995; 27 1395-1400
73 Price L H, Spencer D D, Marek K L. Psychiatric status after human fetal mesencephalic tissue transplantation in Parkinson's disease. Biol Psychiatry . 1995; 38 498-505
74 Kopyov O V, Jacques D S, Lieberman A, Duma C M, Rogers R L. Outcome following intrastriatal fetal mesencephalic grafts for Parkinson's patients is directly related to the volume of grafted tissue. Exp Neurol . 1997; 146 536-545
75 Lopez-Lozano J J, Bravo G, Brera B. Long-term improvement in patients with severe Parkinson's disease after implantation of fetal ventral mesencephalic tissue in a cavity of the caudate nucleus: 5-year follow up in 10 patients. Clinica Puerta de Hierro Neural Transplantation Group. J Neurosurg . 1997; 86 931-942
76 Kordower J H, Freeman T B, Chen E Y. Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson's disease. Mov Disord . 1998; 13 383-393
77 Hagell P, Schrag A, Piccini P. Sequential bilateral transplantation in Parkinson's disease: effects of the second graft. Brain . 1999; 122 1121-1132
78 Hagell P, Crabb L, Pogarell O. Health-related quality of life following bilateral intrastriatal transplantation in Parkinson's disease. Mov Disord . 2000; 15 224-229
79 Folkerth R D, Durso R. Survival and proliferation of nonneural tissues, with obstruction of cerebral ventricles, in a parkinsonian patient treated with fetal allografts. Neurology . 1996; 46 1219-1225
80 Mamelak A N, Eggerding F A, Oh D S. Fatal cyst formation after fetal mesencephalic allograft transplant for Parkinson's disease. J Neurosurg . 1998; 89 592-598
81 Kordower J H, Freeman T B, Bakay R A, Goetz C G, Olanow C W. Treatment with fetal allografts [letter; comment]. Neurology . 1997; 48 1737-1738
82 Freeman T B, Vawter D E, Leaverton P E. Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson's disease. N Engl J Med . 1999; 341 988-992
83 Kordower J H, Rosenstein J M, Collier T J. Functional fetal nigral grafts in a patient with Parkinson's disease: chemoanatomic, ultrastructural, and metabolic studies. J Comp Neurol . 1996; 370 203-230
84 Kordower J H, Freeman T B, Snow B J. 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 . 1995; 332 1118-1124
85 Kordower J H, Styren S, Clarke M. Fetal grafting for Parkinson's disease: expression of immune markers in two patients with functional fetal nigral implants. Cell Transplant . 1997; 6 213-219
86 Brundin P, Karlsson J, Emgard M. Improving the survival of grafted dopaminergic neurons: a review over current approaches. Cell Transplant . 2000; 9 179-195
87 Hallett M, Litvan I. Evaluation of surgery for Parkinson's disease: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. The Task Force on Surgery for Parkinson's Disease. Neurology . 1999; 53 1910-1921
88 Fahn S, Greene P E, Tsai W. Double-blind controlled trial of human embryonic dopaminergic tissue transplants in advanced Parkinson's disease: clinical outcomes. Neurology . 1999; 52 A405
89 Freed C R, Greene P E, Breeze R E. Transplantation of embryonic dopamine neurons for severe Parkinsons's disease. N Engl J Med . 2001; 344 710-719
90 Hubert G W, Subramanian T, Watts R L, Bakay R AE. Correlation of dopaminergic cell survival to motor behavioral improvement following intrastriatal transplantation of fetal mesencephalic (FM) tissue from a single donor. Neurosci Abstr . 1997; 23-1998
91 Fink J S, Schumacher J M, Ellias S L. Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results. Cell Transplant . 2000; 9 273-278
92 Schumacher J M, Ellias S A, Palmer E P. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology . 2000; 54 1042-1050
93 Dinsmore J H, Pakzaban P, Deacon T W, Burns L, Isacson O. Survival of transplanted porcine neural cells treated with F(ab')2 antibody fragments directed against donor MHC class-I in a rodent model. Transplant Proc . 1996; 28 817-818
94 Jacoby D B, Lindberg C, Ratliff J. Fetal pig neural cells as a restorative therapy for neurodegenerative disease. Artif Organs . 1997; 21 1192-1198
95 Pakzaban P, Deacon T W, Burns L H, Dinsmore J, Isacson O. A novel mode of immunoprotection of neural xenotransplants: masking of donor major histocompatibility complex class I enhances transplant survival in the central nervous system [published erratum appears in Neuroscience 1995;66:761]. Neuroscience . 1995; 65 983-996
96 Brevig T, Holgersson J, Widner H. Xenotransplantation for CNS repair: immunological barriers and strategies to overcome them. Trends Neurosci . 2000; 23 337-344
97 Lund R D, Rao K, Kunz H W, Gill T JD. Immunological considerations in neural transplantation. Transplant Proc . 1989; 21 3159-3162
98 Lund R D, Banerjee R, Rao K. Microglia, MHC expression and graft rejection. Neuropathol Appl Neurobiol . 1994; 20 202-203
99 Pollack I F, Lund R D, Rao K. MHC antigen expression in spontaneous and induced rejection of neural xenografts. Prog Brain Res . 1990; 82 129-140
100 Subramanian T, Pollack I F, Lund R D. The effect of cyclosporine A on eye-removal induced rejection of mesencephalic retinal xenografts. Neurosci Abstr. 1991; 82 1137
101 Subramanian T, Pollack I F, Lund R D. Rejection of mesencephalic retinal xenografts in the rat induced by systemic administration of recombinant interferon-gamma. Exp Neurol . 1995; 131 157-162
102 Widner H, Brundin P, Bjorklund A, Moller E. Immunological aspects of neural grafting in the mammalian central nervous system. Prog Brain Res . 1988; 78 303-307
103 Galpern W R, Burns L H, Deacon T W, Dinsmore J, Isacson O. Xenotransplantation of porcine fetal ventral mesencephalon in a rat model of Parkinson's disease: functional recovery and graft morphology. Exp Neurol . 1996; 140 1-13
104 Michaels M G. Infectious concerns of cross-species transplantation: xenozoonoses. World J Surg . 1997; 21 968-974
105 Michaels M. Xenozoonoses and the xenotransplant recipient. Ann N Y Acad Sci . 1998; 862 100-104
106 Michaels M G. Xenotransplant-associated infections. Lab Anim Sci . 1998; 48 228-233
107 Schumacher J M, Isacson O. Neuronal xenotransplantation in Parkinson's disease [letter]. Nat Med . 1997; 3 474-475
108 Borlongan C V, Su T P, Wang Y. Treatment with delta opioid peptide enhances in vitro and in vivo survival of rat dopaminergic neurons. Neuroreport . 2000; 11 923-926
109 Brundin P, Pogarell O, Hagell P. Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease. Brain . 2000; 123 1380-1390
110 Espejo M, Cutillas B, Arenas T E, Ambrosio S. Increased survival of dopaminergic neurons in striatal grafts of fetal ventral mesencephalic cells exposed to neurotrophin-3 or glial cell line-derived neurotrophic factor. Cell Transplant . 2000; 9 45-53
111 Espejo M, Cutillas B, Ventura F, Ambrosio S. Exposure of foetal mesencephalic cells to bone morphogenetic protein-2 enhances the survival of dopaminergic neurones in rat striatal grafts. Neurosci Lett . 1999; 275 13-16
112 Sautter J, Hoglinger G U, Oertel W H, Earl C D. Systemic treatment with GM1 ganglioside improves survival and function of cryopreserved embryonic midbrain grafted to the 6-hydroxydopamine-lesioned rat striatum. Exp Neurol . 2000; 164 121-129
113 Sautter J, Meyer M, Spenger C, Seiler R W, Widmer H R. Effects of combined BDNF and GDNF treatment on cultured dopaminergic midbrain neurons. Neuroreport . 1998; 9 1093-1096
114 Tornqvist N, Bjorklund L, Almqvist P, Wahlberg L, Stromberg I. Implantation of bioactive growth factor-secreting rods enhances fetal dopaminergic graft survival, outgrowth density, and functional recovery in a rat model of Parkinson's disease. Exp Neurol . 2000; 164 130-138
115 Zawada W M, Zastrow D J, Clarkson E D. Growth factors improve immediate survival of embryonic dopamine neurons after transplantation into rats. Brain Res . 1998; 786 96-103
116 Cheramy A, Chesselet M F, Romo R, Leviel V, Glowinski J. Effects of unilateral electrical stimulation of various thalamic nuclei on the release of dopamine from dendrites and nerve terminals of neurons of the two nigrostriatal dopaminergic pathways. Neuroscience . 1983; 8 767-780
117 Richards C D, Shiroyama T, Kitai S T. Electrophysiological and immunocytochemical characterization of GABA and dopamine neurons in the substantia nigra of the rat. Neuroscience . 1997; 80 545-557
118 Robertson H A. Dopamine receptor interactions: some implications for the treatment of Parkinson's disease. Trends Neurosci . 1992; 15 201-206
119 Santiago M, Westerink B H. The regulation of dopamine release from nigrostriatal neurons in conscious rats: the role of somatodendritic autoreceptors. Eur J Pharmacol . 1991; 204 79-85
120 Nedergaard S, Hopkins C, Greenfield S A. Do nigro-striatal neurones possess a discrete dendritic modulatory mechanism?. <~>Electrophysiological evidence from the actions of amphetamine in brain slices. Exp Brain Res . 1988; 69 444-448
121 Hoffman A F, van Horne G C, Eken S, Hoffer B J, Gerhardt G A. In vivo microdialysis studies on somatodendritic dopamine release in the rat substantia nigra: effects of unilateral 6-OHDA lesions and GDNF. Exp Neurol . 1997; 147 130-141
122 Wictorin K, Simerly R B, Isacson O, Swanson L W, Bjorklund A. Connectivity of striatal grafts implanted into the ibotenic acid-lesioned striatum: III. Efferent projecting graft neurons and their relation to host afferents within the grafts. Neuroscience . 1989; 30 313-330
123 Nikkhah G, Bentlage C, Cunningham M G, Bjorklund A. Intranigral fetal dopamine grafts induce behavioral compensation in the rat Parkinson model. J Neurosci . 1994; 14 3449-3461
124 Nikkhah G, Cunningham M G, McKay R, Bjorklund A. Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions: II. Transplant-induced behavioral recovery. J Neurosci . 1995; 15 3562-3570
125 Johnston R E, Hu X T, White F J, Becker J B. Intrastriatal grafts of fetal ventral mesencephalic tissue restore quantitative and qualitative D1/D2 dopamine receptor synergism in the striatum. Restor Neurol Neurosci . 1997; 11 13-20
126 Johnston R E, Becker J B. Intranigral grafts of fetal ventral mesencephalic tissue in adult 6-hydroxydopamine-lesioned rats can induce behavioral recovery. Cell Transplant . 1997; 6 267-276
127 Yurek D M. Intranigral transplants of fetal ventral mesencephalic tissue attenuate D1-agonist-induced rotational behavior. Exp Neurol . 1997; 143 1-9
128 Mendez I, Sadi D, Hong M. Reconstruction of the nigrostriatal pathway by simultaneous intrastriatal and intranigral dopaminergic transplants. J Neurosci . 1996; 16 7216-7227
129 Wichmann T, Bergman H, Starr P A. Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substantia nigra pars reticulata in primates. Exp Brain Res . 1999; 125 397-409
130 Starr P A, Subramanian T, Bakay R A, Wichmann T. Electrophysiological localization of the substantia nigra in the parkinsonian nonhuman primate. J Neurosurg . 2000; 93 704-710
131 Burris J F. Placebo surgery in trials of therapy for Parkinson's disease [letter; comment]. N Engl J Med . 2000; 342-353 discussion 354-355
132 Freed C R, Breeze R E, Fahn S. Placebo surgery in trials of therapy for Parkinson's disease [letter]. N Engl J Med. 2000; 342-353 discussion 354-355
133 Horisberger J D. Placebo surgery in trials of therapy for Parkinson's disease [letter]. N Engl J Med . 2000; 342 354-355
134 Slattery J. Placebo surgery in trials of therapy for Parkinson's disease [letter; comment]. N Engl J Med . 2000; 342 354-discussion 355
135 Weiner W J. Placebo surgery in trials of therapy for Parkinson's disease [letter; comment]. N Engl J Med . 2000; 342 353-discussion 355
136 Benabid A L, Benazzouz A, Limousin P. Dyskinesias and the subthalamic nucleus. Ann Neurol . 2000; S189-S192 (S189-S192)