Brain derived neurotrophic factor treatment reduces inflammation and apoptosis in experimental allergic encephalomyelitis
Brain derived neurotrophic factor treatment reduces inflammation and apoptosis in experimental allergic encephalomyelitis
复制标题
DOI：
10.1016/j.jns.2008.02.011
复制
发表时间：
2008-07-15
影响因子：
4.4
通讯作者：
Bever, Christopher T.
中科院分区：
文献类型：
--
作者：
Makar, Tapas K.;Trisler, David;Bever, Christopher T.
多发性硬化症是一种中枢神经系统(CNS)炎症性疾病，其中包括神经退行性疾病。脑源性神经营养因子(BDNF)是一种神经保护剂，可能有助于防止神经退行性变，但由于血脑屏障限制其进入中枢神经系统，其应用受到限制。我们利用转化的骨髓干细胞(BMSC)开发了一种新型的BDNF递送系统，并进行了EAE的研究，以确定BDNF的递送是否可以减少炎症和细胞凋亡。与接受不产生BDNF的BMSC的对照组小鼠相比，接受产生BDNF的BMSC的小鼠的临床损害较少。脑和脊髓的病理检查显示，与对照组相比，治疗组小鼠的炎性浸润性细胞减少。原位末端标记法和裂解半胱氨酸天冬氨酸氨基转移酶-3染色显示大鼠脑和脊髓细胞凋亡减少。与已知的脑源性神经营养因子促进细胞凋亡的机制一致，BDNF治疗组小鼠的Bcl2和Akt表达增加。进一步的研究表明，这些增加可能是通过抑制caspase依赖和caspase非依赖的途径来实现的。这些结果表明，转化的骨髓干细胞运送的BDNF减轻了该模型的临床严重度、炎症和细胞凋亡。爱思唯尔出版公司(Elsevier B.V.)
Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) which includes a neurodegenerative component. Brain derived neurotrophic factor (BDNF) is a neuroprotective agent which might be useful in preventing neurodegeneration but its application has been limited because the blood brain barrier restricts its access to the CNS. We have developed a novel delivery system for BDNF using transformed bone marrow stem cells (BMSC) and undertook studies of EAE to determine whether the delivery of BDNF could reduce inflammation and apoptosis. Mice receiving BDNF producing BMSC had reduced clinical impairment compared to control mice receiving BMSC that did not produce BDNF. Pathological examination of brain and spinal cord showed a reduction in inflammatory infiltrating cells in treated compared to control mice. Apoptosis was reduced in brain and spinal cord based on TUNEL and cleaved Caspase-3 staining. Consistent with the known mechanism of action of BDNF on apoptosis, Bcl-2 and Akt were increased in treated mice. Further studies suggested that these increases could be mediated by inhibition of both caspase dependent and caspase independent pathways. These results suggest that the BDNF delivered by the transformed bone marrow stem cells reduced clinical severity, inflammation and apoptosis in this model. Published by Elsevier B.V.