Zanirati Gabriele, Azevedo Pamella Nunes, Marinowic Daniel Rodrigo, Rodrigues Felipe, de Oliveira Dias Ana Christina, Venturin Gianina Teribele, Greggio Samuel, Simão Fabrício, DaCosta Jaderson Costa
PUCRS, Pós-Graduação em Medicina e Ciências da Saúde, Instituto do Cérebro do Rio Grande do Sul (InsCer), Instituto de Pesquisas Biomódicas, Laboratório de Neurociências e Sinalização Celular, Porto Alegre, RS, Brazil.
CNS Neurosci Ther. 2015 May;21(5):463-71. doi: 10.1111/cns.12382. Epub 2015 Jan 29.
In previous studies, transplantation of bone marrow mononuclear cells (BMMCs) in epileptic animals has been found to be neuroprotective. However, the mechanism by which the BMMCs act remains unclear. We hypothesize that BMMCs may provide neuroprotection to the epileptic brain through trophic support. To test our hypothesis, we studied the temporal expression of neurotrophins after BMMC transplantation in the epileptic rat hippocampus.
Chronically epileptic rats were intravenously transplanted with 1 × 10(7) BMMCs isolated from GFP transgenic mice. Expression levels of BDNF, GDNF, NGF, VEGF, and TGF-β1, and their receptors, were evaluated by ELISA and/or qRT-PCR analysis.
Our data revealed increased protein expression of BDNF, GDNF, NGF, and VEGF and reduced levels of TGF-β1 in the hippocampus of transplanted epileptic animals. Additionally, an increase in the mRNA expression of BDNF, GDNF, and VEGF, a reduction in TGF-β1, and a decrease in mRNA levels of the TrkA and TGFR-β1 receptors were also observed.
The gain provided by transplanted BMMCs in the epileptic brain may be related to the ability of these cells in modulating the network of neurotrophins and angiogenic signals.
在先前的研究中，已发现将骨髓单个核细胞（BMMCs）移植到癫痫动物体内具有神经保护作用。然而，BMMCs发挥作用的机制仍不清楚。我们推测BMMCs可能通过营养支持为癫痫脑提供神经保护。为了验证我们的假设，我们研究了癫痫大鼠海马体中BMMC移植后神经营养因子的时间表达情况。
将从绿色荧光蛋白转基因小鼠分离得到的1×10⁷个BMMCs静脉注射到慢性癫痫大鼠体内。通过酶联免疫吸附测定（ELISA）和/或定量逆转录聚合酶链反应（qRT-PCR）分析评估脑源性神经营养因子（BDNF）、胶质细胞源性神经营养因子（GDNF）、神经生长因子（NGF）、血管内皮生长因子（VEGF）和转化生长因子-β1（TGF-β1）及其受体的表达水平。
我们的数据显示，移植后的癫痫动物海马体中BDNF、GDNF、NGF和VEGF的蛋白表达增加，TGF-β1水平降低。此外，还观察到BDNF、GDNF和VEGF的mRNA表达增加，TGF-β1减少，以及TrkA和TGFR-β1受体的mRNA水平降低。
移植的BMMCs在癫痫脑中所提供的益处可能与这些细胞调节神经营养因子和血管生成信号网络的能力有关。
