Intrastriatal administration of erythropoietin protects dopaminergic neurons and improves neurobehavioral outcome in a rat model of Parkinson's disease.
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.
Xue
Y-Q
YQ
Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Zhao
L-R
LR
Guo
W-P
WP
Duan
W-M
WM
D000818:Animals; D000893:Anti-Inflammatory Agents; D001253:Astrocytes / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D002452:Cell Count; D003720:Densitometry; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004921:Erythropoietin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics; D007150:Immunohistochemistry; D017628:Microglia / Q000378:metabolism; D008845:Microinjections; D017072:Neostriatum / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000473:pathology* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000473:pathology
D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D004921:Erythropoietin; D016627:Oxidopamine; D004298:Dopamine