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Intrastriatal administration of erythropoietin protects dopaminergic neurons and improves neurobehavioral outcome in a rat model of Parkinson's disease.

Abstract
Erythropoietin (EPO), a hematopoietic cytokine, has recently been demonstrated to protect nigral dopaminergic neurons in a mouse model of Parkinson's disease (PD). In the present study, we tested the hypothesis that recombinant human erythropoietin (rhEPO) could protect dopaminergic neurons and improve neurobehavioral outcome in a rat model of PD. rhEPO (20 units in 2 microl of vehicle) was stereotaxically injected into one side of the striatum. 6-hydroxydopamine (6-OHDA) was injected into the same side 1 day later. Another group of rats received rhEPO (5000 u/kg, i.p.) daily for 8 days, and unilateral injection of 6-OHDA in the striatum 3 days after systemic administration of rhEPO. We observed that intrastriatal administration, but not systemic administration of rhEPO significantly reduced the degree of rotational asymmetry. The rhEPO-treated rats also showed an improvement in skilled forelimb use when compared with control rats. The number of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons in the ipsilateral substantia nigra (SN) was significantly larger in intrastriatal rhEPO-treated rats than that in control rats. TH-IR fibers in the 6-OHDA-lesioned striatum were also increased in the intrastriatal rhEPO-treated rats when compared with control rats. In addition, there were lower levels of expression of major histocompatibility complex (MHC) class II antigens and a smaller number of activated microglia in the ipsilateral SN in intrastriatal rhEPO-treated rats than that in control rats at 2 weeks, suggesting that intrastriatal injection of rhEPO attenuated 6-OHDA-induced inflammation in the ipsilateral SN. Our results suggest that intrastriatal administration of rhEPO can protect nigral dopaminergic neurons from cell death induced by 6-OHDA and improve neurobehavioral outcome in a rat model of PD. Anti-inflammation may be one of mechanisms responsible for rhEPO neuroprotection.
AuthorsY-Q Xue, L-R Zhao, W-P Guo, W-M Duan
JournalNeuroscience (Neuroscience) Vol. 146 Issue 3 Pg. 1245-58 (May 25 2007) ISSN: 0306-4522 [Print] United States
PMID17363174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • Erythropoietin
  • Oxidopamine
  • Dopamine
Topics
  • Animals
  • Anti-Inflammatory Agents
  • Astrocytes (metabolism)
  • Behavior, Animal (drug effects)
  • Cell Count
  • Densitometry
  • Dopamine (metabolism, physiology)
  • Erythropoietin (administration & dosage, pharmacology, therapeutic use)
  • Female
  • Genes, MHC Class I (genetics)
  • Genes, MHC Class II (genetics)
  • Immunohistochemistry
  • Microglia (metabolism)
  • Microinjections
  • Neostriatum (metabolism, physiology)
  • Neurons (pathology)
  • Neuroprotective Agents
  • Oxidopamine
  • Parkinson Disease, Secondary (drug therapy, pathology, psychology)
  • Rats
  • Rats, Sprague-Dawley
  • Stereotyped Behavior (drug effects)
  • Substantia Nigra (pathology)

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