Transplantation of Human Dopaminergic Neurons in Parkinsonism: Experimental Reality and Future Clinical Feasibility

  • Ake Seiger
  • Lars Olson
  • Ingrid Stromberg
  • Marc Bygdeman
  • Menek Goldstein
  • Barry Hoffer

Abstract

The extensive degeneration of mesostriatal dopamine (DA) neurons in patients with Parkinson’s disease lead to severe motor deficits with tremor, rigidity and hypokinesia. Levodopa treatment counteracts many of these symptoms for a few years, but patients invariably go into an end stage of severe “on-off” oscillations irrespective of further modulations of the medication (Marsden 1980). The need for a new and more effective long-term treatment of Parkinson’s disease is therefore urgent. After unilateral electrolytic lesions of the nigrostriatal pathway that cause degeneration of striatal DA terminals, rats become asymmetric and display a rotational behavior when given drugs that interfere with DA neurotransmission (Anden et al 1966). Animal models of Parkinson’s disease based on these observations have been available for almost 20 years. The first one was the 6-hydroxy-dopamine (6-OH-DA) lesion of the nigrostriatal pathway in rats (Ungerstedt 1971). By specific unilateral lesions of the DA system, rats have been produced whose asymmetric motor behavior can be quantified by a rotometer (Ungerstedt and Arbuthnott 1970). It was later shown that the transplantation of fetal syngeneic DA neuroblasts from substantia nigra to animals with such lesions resulted in a partial structural and functional restoration of the DA system in striatum (Perlow et al., 1979, Bjorklund and Stenevi 1979). Later modification of the procedure has improved reinnervation of striatum from the grafted DA neuroblasts leading to extensive functional restitution of the motor performance of the lesioned animals, (reviews see: Olson et al., 1985, Brundin et al., 1987).

Keywords

Dopamine Neurol Cyclosporin Catecholamine Levodopa 

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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Ake Seiger
    • 1
  • Lars Olson
    • 2
  • Ingrid Stromberg
    • 2
  • Marc Bygdeman
    • 3
  • Menek Goldstein
    • 4
  • Barry Hoffer
    • 5
  1. 1.Department of Neurological SurgeryUniversity of Miami, School of MedicineMiamiUSA
  2. 2.Department of Histology and NeurobiologyKarolinska InstituteStockholmSweden
  3. 3.Department of Obstetrics and GynecologyKarolinska InstituteStockholmSweden
  4. 4.Department of PsychiatryNew York University Medical CenterNewYorkUSA
  5. 5.Department of PharmacologyUniversity of Colorado Medical CenterDenverUSA

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