Vasoactive intestinal peptide prevents activated microglia-induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma
Vasoactive intestinal peptide prevents activated microglia-induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma
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DOI：
10.1096/fj.02-1029fje
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发表时间：
2003-08-01
期刊：
影响因子：
4.8
通讯作者：
Ganea, D
中科院分区：
文献类型：
--
作者：
Delgado, M;Ganea, D
在大多数神经退行性疾病中，包括多发性硬化症、帕金森氏病和阿尔茨海默病，大量神经细胞死亡是由于不受控制的炎症反应造成的，其中激活的小胶质细胞及其细胞毒剂起着关键的病理作用。由于目前对这些疾病的治疗并不有效，最近几个被称为“小胶质细胞失活因子”的调节分子成为相当多研究的焦点。血管活性肠肽(VIP)是一种具有强大抗炎作用的神经肽，已被发现对内毒素休克和类风湿关节炎等其他炎症性疾病具有保护作用。在本研究中，我们研究了VIP在体外和体内对炎症介导的神经退行性变的影响，以及在涉及中枢神经系统(CNS)炎症的实验性病理条件下(如脑损伤)VIP的神经保护作用。激活的小胶质细胞及其衍生的细胞毒产物的参与也被研究。VIP通过抑制小胶质细胞衍生的致炎因子(肿瘤坏死因子α、白介素1β、一氧化氮)的产生，对炎症状态具有明显的神经保护作用。在这个意义上，VIP通过减少邻近小胶质细胞的炎症反应来防止脑创伤后神经细胞的死亡。因此，VIP作为一种有价值的神经保护剂出现在治疗炎症诱导的神经变性发生的中枢神经系统的病理条件下。
In most neurodegenerative disorders, including multiple sclerosis, Parkinson's disease, and Alzheimer's disease, a massive neuronal cell death occurs as a consequence of an uncontrolled inflammatory response, where activated microglia and its cytotoxic agents play a crucial pathologic role. Because current treatments for these diseases are not effective, several regulatory molecules termed "microglia-deactivating factors" recently have been the focus of considerable research. Vasoactive intestinal peptide ( VIP) is a neuropeptide with a potent antiinflammatory effect, which has been found to protect from other inflammatory disorders, such as endotoxic shock and rheumatoid arthritis. In the present study, we investigate the effect of VIP on inflammation-mediated neurodegeneration in vitro and in vivo as well as on the putative neuroprotective effect of VIP on experimental pathological conditions in which central nervous system (CNS) inflammation is involved, such as brain trauma. The involvement of activated microglia and their derived cytotoxic products is also studied. VIP has a clear neuroprotective effect on inflammatory conditions by inhibiting the production of microglia-derived proinflammatory factors (tumor necrosis factor alpha, interleukin-1beta, nitric oxide). In this sense, VIP prevents neuronal cell death following brain trauma by reducing the inflammatory response of neighboring microglia. Therefore, VIP emerges as a valuable neuroprotective agent for the treatment of pathologic conditions of the CNS where inflammation-induced neurodegeneration occurs.