摘要
小神经胶质和一些炎症细胞因子及神经生长因子与创伤性脑损伤有关。alpha肿瘤坏死因子(TNF-α)可以通过小胶质细胞,星形胶质细胞和神经元被释放。TNF-α已经被报道为既具有促神经性又具有抗神经性的,这取决于模式、方法和细胞衍生区域。有两种亚型小胶质细胞:M1和M2。前者(非噬菌细胞的小神经胶质细胞的M1亚型)能够分泌较高水平的TNF-α,但是低水平的白介素(IL)-10(IL-10),一种抗炎细胞因子。促炎和促凋亡功能也可以通过激活肿瘤坏死因子受体1(TNF-R1)来促进。相比之下,M2激活产生低水平的TNF-α但是较高水平的IL-10。TNFR2的激活可以提升促生长和生存途径的促进。在TBI的急性期,小胶质细胞和TNF-R1的M1亚型被激活从而产生较高水平的TNF-α 和较低水平的IL-10,从而导致神经抑制,神经元缺失和器官功能障碍的发生(所谓的小胶质细胞激活I)。相比之下,M2亚型的小胶质细胞和TNF-R2的激活能够促进神经形成和组织复原(所谓的小胶质细胞激活II)。TBI的严重程度取决于小胶质细胞激活I和小胶质细胞激活II的有效效应。事实上,通过使用TBI啮齿动物模型,疗效评价研究表明,一些药物或战略是通过抑制M1亚型和TNF-R1小胶质细胞活化来减小脑容量损伤和神经功能缺陷,从而降低小神经胶质细胞的激活I应答,但是它可能通过激活M2亚型和TNF-R2来促进神经再生和功能恢复。因此,基于对小胶质细胞应答I和II,我们推断将来的研究可能集中于最佳的TBI的多治疗药物和策略的治疗。
关键词: 大脑,细胞因子,自由基,小神经胶质,外伤
Current Medicinal Chemistry
Title:Microglial Activation as a Compelling Target for Treating Acute Traumatic Brain Injury
Volume: 22 Issue: 6
Author(s): Chung-Ching Chio, Mao-Tsun Lin and Ching-Ping Chang
Affiliation:
关键词: 大脑,细胞因子,自由基,小神经胶质,外伤
摘要: Microglia and several inflammatory cytokines and neurotrophic growth factors are involved in traumatic brain injury (TBI). Tumor necrosis factor-alpha (TNF-α) can be released by microglia, astrocytes, and neurons. TNF-α has been reported to be both proneurogenic and antineurogenic, depending upon the model, method, and cell-derived region. There are two subtypes of microglia: M1 and M2. The former (or M1 subtype of non-phagocytic microglia) is able to secrete higher levels of TNF-α but lower levels of interleukin (IL)-10 (IL-10), an anti-inflammatory cytokine. Both the proinflammatory and the pro-apoptotic function can also be promoted by activation of tumor necrosis factor-receptor 1 (TNF-R1). In contrast, M2 activation produces lower levels of TNF-α but higher levels of IL-10. Pro-growth and survival pathways can be promoted by the activation of TNFR2. During the acute stage of TBI, both M1 subtype of microglia and TNF-R1 are activated to cause higher levels of TNF-α but lower levels of IL-10, which lead to suppressed neurogenesis, neuronal loss and organ dysfunction (so-called microglial activation I). In contrast, activation of both M2 subtype of microglia and TNF-R2 is able to promote neurogenesis and tissue recovery (so-called microglial activation II). The severity of TBI depends upon the net effects between microglial activation I and microglial activation II. Indeed, by using rodent models of TBI, therapeutic evaluation studies reveal that several agents or strategies attenuate contused brain volume and neurological deficits by inhibiting microglial activation I but inducing microglial activation II. For example, etanercept therapy might attenuate contused brain volume and neurological deficits by inactivating the M1 subtype and TNF-R1 to reduce the microglial activation I response, but it might promote neurogenesis and functional recovery by activating the M2 subtype and TNF-R2. Therefore, based on microglial responses I and II, we conclude that future studies should focus on multiple therapeutic agents and strategies for optimal TBI therapy.
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Cite this article as:
Chung-Ching Chio, Mao-Tsun Lin and Ching-Ping Chang , Microglial Activation as a Compelling Target for Treating Acute Traumatic Brain Injury, Current Medicinal Chemistry 2015; 22 (6) . https://dx.doi.org/10.2174/0929867321666141106124657
DOI https://dx.doi.org/10.2174/0929867321666141106124657 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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