小膠質細胞位於中樞神經系統為具有吞噬能力的膠質細胞，當腦部組織受到外來損傷時，會引發小膠質細胞的活化進而釋出大量的前發炎因子，進而擴大中樞神經系統的傷害；但是活化的小膠質細胞也會進行吞噬作用清除細胞碎片，並且分泌出神經滋養因子來幫助組織重組。過去研究指出，神經滋養因子可調節發育階段神經元細胞的生長、分化以及突觸的可塑性，又可促進損傷後神經系統的修復；除了神經元細胞之外，膠質細胞不僅可分泌出神經滋養因子，也會表現出其專一性的接受器。然而這些神經滋養因子對於小膠質細胞的調控仍未被深入探討，因此本實驗分為三部份探討神經滋養因子及神經保護藥物對於小膠質細胞的影響：(一) 前處理NT-3於小膠質細胞，可降低由LPS所誘導的NF-κB與DNA結合能力並抑制小膠質細胞吞噬作用之能力。(二) 分別利用GDNF及CNTF處理小膠質細胞，結果發現GDNF可增加細胞內鈣離子濃度及小膠質細胞吞噬作用能力；同樣地，CNTF會增強小膠質細胞的吞噬作用能力，其機制推測透過提升其細胞內鈣離子濃度以及整合蛋白αV的表現；因此可知CNTF及GDNF促進小膠質細胞的吞噬作用為一鈣離子依賴性的機制。(三) 抗癲癇藥物VPA具有神經保護的功效，實驗中發現VPA不會引起小膠質細胞的發炎活化反應，但可增加其吞噬作用的能力。綜合以上結果，推測神經滋養因子及VPA可降低小膠質細胞的發炎反應，更可增加其吞噬作用的能力，而幫助損傷後的中樞神經系統進行組織重組。

Microglia, macrophages of the central nervous system (CNS), are activated following CNS injury and produce proinflammatory mediators which enhance the occurrence of neural degeneration. Yet, activated microglia play a constructive role in tissue remodeling and repair via engulfing cell/tissue debris and secreting neurotrophic/growth factors. Neurotrophic factors (NTs) act as survival factors for neurons, and induce neuronal maturation, and synaptic plasticity in developing CNS. Accordingly, NTs hold a promising effect on neuronal survival and system recovery after CNS injury. In addition to neurons, glia are not only NT-producing cells, but also express their specific receptors. However, little is known whether microglial activity can be mediated by NTs, and subsequently contribute to the protective effect of NTs on neurons and tissue repair in the injured CNS. Here we found that pretreatment with NT-3 pretreatment (pre NT-3) induce inhibition of nucleus factor kappa B (NF-B) activation in lipopolysaccharide (LPS)-treated microglia, which may in turn reduce LPS-induced activation of microglia. Yet, we also observed that microglial phagocytotic ability was slightly attenuated by preNT-3 followed by LPS treatment. On the other hand, treatment with GDNF induced an increase in microglia phagocytotic ability, which is possibly resulted from GDNF-induced increase in [Ca2+]i. Similarly, CNTF increased microglial phagocytotic ability and the expression of integrin av , and [Ca2+]i rise. We also examine whether synthesized neuroprotective drugs can mediate microglial phagocytosis. VPA(Valproic acid), a common anti-seizure drug, did not induce mciroglial inflammatory response. In addition, VPA could enhance microglial phagocytotic ability. Collectively, NTs and VPA can either reduce the production of microglial proinflammatory mediator or enhance microglial phagocytosis to improve neuronal survival and tissue repair.

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