Blood-brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons

被引：110

作者：

Rite, Inmaculada ^{[1
]}

Machado, Alberto ^{[1
]}

Cano, Josefina ^{[1
]}

Venero, Jose L. ^{[1
]}

机构：

[1] Univ Seville, Fac Farm, Dept Bioquim Bromatol Toxicol & Med Legal, E-41012 Seville, Spain

来源：

JOURNAL OF NEUROCHEMISTRY | 2007年 / 101卷 / 06期

关键词：

apoptosis; microglia activation; Parkinson's disease; tyrosine hydroxylase loss; vascular endothelial growth factor; ventral mesencephalon;

D O I：

10.1111/j.1471-4159.2007.04567.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have evaluated the possibility that changes in the vascular system may constitute a contributing factor for the death of nigral dopaminergic neurons in Parkinson's disease. Thus, we have employed intranigral injections of vascular endothelial growth factor (VEGF), the most potent inducer of blood-brain barrier (BBB) permeability. A single dose of 1 mu g of VEGF, chosen from a dose-response study, highly disrupted the BBB in the ventral mesencephalon in a time-dependent manner. A strong regional correlation between BBB disruption and loss of tyrosine hydroxylase-positive neurons was evident. Moreover, Fluoro-Jade B labelling showed the presence of dying neurons in the substantia nigra in response to VEGF injection. High number of TUNEL-positive nuclei was observed in this area along with activation of caspase 3 within nigral dopaminergic neurons. Analysis of the glial population demonstrated a strong inflammatory response and activation of astroglia in response to BBB disruption. We conclude that disruption of the BBB may be a causative factor for degeneration of nigral dopaminergic neurons.

引用

页码：1567 / 1582

页数：16

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