Continuous intraventricular infusion of erythropoietin exerts neuroprotective/rescue effects upon Parkinson's disease model of rats with enhanced neurogenesis

被引：44

作者：

Kadota, Tomohito ^{[1
]}

Shingo, Tetsuro ^{[1
]}

Yasuhara, Takao ^{[1
]}

Tajiri, Naoki ^{[1
]}

Kondo, Akihiko ^{[1
]}

Morimoto, Takamasa ^{[1
]}

Yuan, Wen Ji ^{[1
]}

Wang, Feifei ^{[1
]}

Baba, Tanefumi ^{[1
]}

Tokunaga, Koji ^{[1
]}

Miyoshi, Yasuyuki ^{[1
]}

Date, Isao ^{[1
]}

机构：

[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg, Okayama 7008558, Japan

来源：

BRAIN RESEARCH | 2009年 / 1254卷

关键词：

6-OHDA; Apoptosis; Dopaminergic neuron; Neurogenesis; Subventricular zone; NEURAL STEM-CELLS; CEREBRAL-ISCHEMIA; DOPAMINERGIC-NEURONS; RODENT MODEL; TRANSPLANTATION; PROTECTS; PROLIFERATION; THERAPY; STROKE; INJURY;

D O I：

10.1016/j.brainres.2008.11.094

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neuronal systems. Several therapeutic tools for PD include medication using L-DOPA and surgeries such as deep brain stimulation are established. However, the therapies are considered as symptomatic therapy, but not basic remedy for PD and a new regenerative therapy would be desired to explore. In this study, the neuroprotective/rescue effects of erythropoietin (EPO), a well known hematopoietic hormone, on dopaminergic neurons were explored with neurogeneic potencies of EPO. EPO (100 IU/day) was continuously administered with micro-osmotic pump for a week to PD model of rats induced by intrastriatal 6-hydroxydopamine (6-OHDA) injection with subsequent behavioral and immunohistochemical investigations. The number of amphetamine-induced rotations of EPO-treated rats significantly decreased, compared to the control rats. The preservation of dopaminergic neurons of EPO-treated rats were confirmed by tyrosine hydroxylase staining and Fluoro-Gold staining. The number of bromodeoxyuridine (BrdU)/polysialic acid-neural cell adhesion molecule (PSA-NCAM) double positive cells in the subventricular zone of EPO-treated rats significantly increased with migratory potencies to the damaged striatum, compared to the control rats. Furthermore, TUNEL staining and phosphorylated Akt staining revealed that the neuroprotective/rescue effects of EPO might be mediated by anti-apoptotic effects through the increase of phosphorylated Akt. These results suggest that continuous low dose infusion of EPO exerts neuroprotective/rescue effects with neurogeneic potentials. EPO might be a strong tool for PD therapy, although the further experiments should be added. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：120 / 127

页数：8

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