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.
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Authors | Y-Q Xue, L-R Zhao, W-P Guo, W-M Duan |
Journal | Neuroscience
(Neuroscience)
Vol. 146
Issue 3
Pg. 1245-58
(May 25 2007)
ISSN: 0306-4522 [Print] United States |
PMID | 17363174
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Anti-Inflammatory Agents
- Neuroprotective Agents
- Erythropoietin
- Oxidopamine
- Dopamine
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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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