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Graft placement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia.

In English

Författare

Summary, in English

In two recent double-blind clinical trials of fetal ventral mesencephalic cell transplants into the striatum in patients with Parkinson's disease (PD), a significant proportion of the grafted patients developed dyskinetic side effects, which were not seen in the sham operated patients. Comparison between dyskinetic and non-dyskinetic grafted patients in one of the trials suggested that an uneven pattern of striatal reinnervation might be the leading cause of the dyskinesias. Here, we studied the importance of graft placement for the development of dyskinesias in parkinsonian rats. Abnormal involuntary movements resembling peak-dose dyskinesias seen in PD patients were induced by daily injections of L-DOPA for 6 weeks. The dyskinetic animals received about 130.000 fetal ventral mesencephalic cells as single grafts placement in the rostral or the caudal aspect of the head of striatum. The results show that grafts placed in the caudal, but not the rostral, part are effective in reducing the L-DOPA-induced limb and orolingual dyskinesia, predominantly seen as hyperkinesia. The same grafts, however, also induced a new type of dyskinetic behavior after activation with amphetamine, which were not seen in non-grafted lesion controls. The severity of these abnormal involuntary movements was significantly correlated with a higher graft-derived dopaminergic reinnervation in the caudal aspect of the head of striatum relative to the rostral part. The results indicate that graft-induced dyskinesias in PD patients may be linked to single, small graft deposits that provide an uneven, patchy reinnervation of the putamen.

Publiceringsår

2006

Språk

Engelska

Sidor

657-668

Publikation/Tidskrift/Serie

Neurobiology of Disease

Volym

21

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Neurosciences

Nyckelord

  • Ventral mesenchephalon
  • Cell transplantation
  • Dyskinesia
  • l-DOPA
  • Parkinson's disease
  • Motor behavior

Status

Published

Forskningsgrupp

  • Brain Repair and Imaging in Neural Systems (BRAINS)
  • Basal Ganglia Pathophysiology
  • Neurobiology

ISBN/ISSN/Övrigt

  • ISSN: 0969-9961