Torp Reidun, Singh Preet Bano, Sørensen Dag R, Dietrichs Espen, Hirschberg Henry
Centre for Molecular Biology and Neuroscience (CMBN), Universitetet i Oslo, Postboks 1105 Blindern, 0317 Oslo.
Tidsskr Nor Laegeforen. 2006 Mar 23;126(7):899-901.
One of several probable causation theories of Parkinson disease postulates that brain tissue cannot generate sufficient levels of various growth factors required to sustain the viability of dopamine-producing nerve cells in the presence of as yet unknown toxic factors. The study reported here evaluates the ability of externally applied growth factors to protect the dopamine fibres in the basal ganglia in a toxin-induced animal model of the disease.
All animals (rats) were subjected to selective destruction of the dopamine-producing cells in substantia nigra. The rats were divided into three groups. Two groups received intracerebral treatment with either glia-cell derived neurotrophic factor (GDNF) or a combination of brain-derived neurotrophic factor (BDNF) and GDNF. The third group acted as untreated controls and were given sterile saline. The growth factors were infused directly into the brain by an osmotic pump over a period of 28 days. Brain sections taken from all three groups were evaluated by immunocytochemistry.
The two groups of rats that received growth factor infusion displayed a significant improvement in their motor behaviour compared to control animals. Immunocytochemistry studies demonstrated that the group receiving a combination of GDNF and BDNF had an increased number of surviving active fibres in the dopamine system striatum in comparison to the control and GDNF groups. In addition the infusion of growth factors resulted in a proliferation of subventricular cells in the basal ganglia.
The improved motor function following growth factor treatment in this rat model might be due to a delayed retrograde degeneration of the nigrostriatal nerve fibers. Growth factor infusion also clearly stimulated endogenous stem cells and caused their migration towards the striatum. Our observations indicate that the infusion of growth factors into the brain have a symptomatic and neuroprotective effect in this model.
帕金森病几种可能的病因理论之一假定，在存在尚不明确的毒性因素的情况下，脑组织无法产生维持多巴胺能神经细胞存活所需的足够水平的各种生长因子。本文报道的研究评估了在毒素诱导的该疾病动物模型中，外部应用生长因子保护基底神经节中多巴胺纤维的能力。
所有动物（大鼠）均经历黑质中多巴胺能细胞的选择性破坏。大鼠被分为三组。两组分别接受脑内注射胶质细胞源性神经营养因子（GDNF）或脑源性神经营养因子（BDNF）与GDNF的组合。第三组作为未治疗的对照组，给予无菌生理盐水。生长因子通过渗透泵在28天内直接注入脑内。对所有三组动物的脑切片进行免疫细胞化学评估。
与对照动物相比，接受生长因子注射的两组大鼠的运动行为有显著改善。免疫细胞化学研究表明，与对照组和GDNF组相比，接受GDNF和BDNF组合的组在多巴胺系统纹状体中存活的活性纤维数量增加。此外，生长因子的注入导致基底神经节脑室下区细胞增殖。
在该大鼠模型中生长因子治疗后运动功能的改善可能是由于黑质纹状体神经纤维逆行性变性延迟。生长因子的注入也明显刺激了内源性干细胞并导致它们向纹状体迁移。我们的观察结果表明，向脑内注入生长因子在该模型中具有对症和神经保护作用。
