Continuous subcutaneous infusion of pramipexole protects against lipopolysaccharide-induced dopaminergic cell death without affecting the inflammatory response

Iravani M. M., Sadeghian M., Leung C., TEL B. C., Rose S., Schapira A. H., ...More

EXPERIMENTAL NEUROLOGY, vol.212, no.2, pp.522-531, 2008 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 212 Issue: 2
  • Publication Date: 2008
  • Doi Number: 10.1016/j.expneurol.2008.04.037
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.522-531
  • Hacettepe University Affiliated: Yes


The D2/D3 dopamine receptor agonist pramipexole, protects against toxin-induced dopaminergic neuronal destruction but its mechanism of action is unknown. Inflammation following glial cell activation contributes to cell death in Parkinson's disease and we now report on the effects of acute or chronic administration of pramipexole on lipopolysaccharide (LPS) induced inflammation and nigral dopaminergic cell death in the rat. At 48 h and 30 days following supranigral administration of LPS, approximately 70% of tyrosine hydroxylase (TH) immunoreactive (-ir) cells in substantia nigra had degenerated with a corresponding loss of TH-ir terminals in the striatum. In rats acutely treated with pramipexole (2 x 1 mg/k; s.c.) 48 h following LPS application, there was no difference in the number of TH-ir cells or terminals compared to LPS-treated Fats receiving vehicle. However, the continuous Subcutaneous infusion of pramipexole for 7 days prior to LPS and 21 days subsequently, produced a marked preservation of both TH-ir cells and terminals. At 48 h or 30 days, LPS induced an up-regulation of ubiquitin-ir within the nigral TH-ir neurons, which was reduced by pramipexole treatment. Thirty days following supranigral LPS administration (9 days after the end of infusion), (+)-amphetamine (5 mg/kg, i.p.) caused robust ipsiversive rotation. In rats treated with LPS but receiving continuous subcutaneous administration of pramipexole, (+)-amphetamine-induced rotation was markedly reduced. LPS-induced increase in the levels of inflammatory markers, were not affected by either acute administration or Continuous infusion of pramipexole. Continuous infusion of pramipexole protected dopaminergic neurones against inflammation induced degeneration but without modification of the inflammatory response. (C) 2008 Elsevier Inc. All rights reserved.