ACM  >> Vol. 4 No. 2 (June 2014)

    免疫机制在脑继发性损伤过程中的作用
    The Role of Immune Mechanism in the Process of Secondary Brain Injury

  • 全文下载: PDF(352KB) HTML    PP.15-21   DOI: 10.12677/ACM.2014.42004  
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作者:  

黄德智,杨金福:中南大学湘雅三医院神经外科, 长沙

关键词:
免疫机制继发性脑损伤脑缺血Immune Mechanism Secondary Brain Injury Cerebral Ischemia

摘要:

目前许多研究表明,免疫反应在大脑缺血后的损伤中扮演着重要的角色。淋巴细胞及固有免疫都不同程度的参与继发性脑细胞损伤的过程,这些免疫细胞被激活后均通过释放相关免疫因子而引起不同程度的大脑缺血损伤及缺血再灌注损伤。而找到这些免疫细胞的相关产物,并干预其在大脑缺血后的表达,则可不同程度减小大脑缺血及缺血再灌注损伤。有关免疫系统对大脑损伤的研究在不断进步,本文将介绍有关免疫系统对大脑损伤近年来的研究进展。

Many studies have shown that the immune response plays an important role in post-ischemic brain injury. Lymphocytes and innate immunity participate in the process of post-ischemic brain injury, and these immune cells are activated through the release of immune factors, which are involved in ischemic injury and ischemia-reperfusion injury. If we find relevant products of these immune cells and interfere its expression in the brain after ischemia, the cerebral ischemia and ischemia-reperfusion injury can be reduced in varying degrees. Research on the effects of immune system on brain injury has made progress. In this paper, the progress of the effects of immune system on brain damage in recent years will be presented.


文章引用:
黄德智, 杨金福. 免疫机制在脑继发性损伤过程中的作用[J]. 临床医学进展, 2014, 4(2): 15-21. http://dx.doi.org/10.12677/ACM.2014.42004

参考文献

[1] Ren, X., Akiyoshi, K., Dziennis, S., et al. (2011) Regulatory B cells limit CNS inflammation and neurologic deficits in mrine experimental stroke. The Journal of Neuroscience, 31, 8556-8563.
[2] Perry, V.H. and Teeling, J. (2013) Mi-croglia and macrophages of the central nervous system: The contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Seminars in Immunopathology, 35, 601-612.
[3] Kato, H. and Walz, W. (2000) The initiation of the microglial response. Brain Research, 10, 137-143.
[4] Cheng, R.D., Ren, J.J., Zhang, Y.Y. and Ye, X.M. (2014) P2X4 receptors expressed on microglial cells in post- ischemic inflammation of brain ischemic injury. Neurochemistry International, 67, 9-13.
[5] Thomas, A.G., O’Driscoll, C.M., Bressler, J., et al. (2014) Small molecule glutaminase inhibitors block glutamate release from stimulated microglia. Biochemical and Biophysical Research Communications, 443, 32-36.
[6] Yu, L. and Liang, W. (2013) Inflammatory response following diffuse axond injury. International Journal of Medical Science, 10, 515-521.
[7] Raivich, G. (2005) Like cops on the beat: The active role of resting microglia. Trends in Neurosciences, 19, 312-318.
[8] Sanz, J.M., Chiozzi, P., Ferrari, D., et al. (2009) Ac-tivation of microglia by amyloid (beta) requires P2X7 receptor expression. The Journal of Immunology, 182, 4378-4385.
[9] Fujita, T., Yoshimine, T., et al. (1998) Cellular dynamics of macrophages and microglial cells in reaction to stab wou- nds in rat cerebral cortex. Acta Neurochirurgica, 140, 275-279.
[10] 黄其林, 张可成 (2001) 脑穿刺伤灶愈合过程中大胶质细胞的变化. 基础医学与临床, 2, 158-162.
[11] Riabov, V., Gudima, A., Wang, N., et al. (2014) Role of tumor associated macrophages in tumor angiogenesis and ly- mphangiogenesis. Frontiers in Phy-siology, 5, 75.
[12] Martin, C.J., Peters, K.N. and Behar, S.M. (2014) Macrophages clean up: Efferocytosis and mi-crobial control. Current Opinion in Microbiology, 17, 17-23.
[13] Meola, D., Huang, Z., Ha, G.K., et al. (2013) Loss of neuronal phenotype and neurodegeneration: Effects of T lymphocytes and brain interleukin-2. Journal of Alzheimer’s Disease & Parkinsonism, 10, 3.
[14] Stichel, C.C. and Luebbert, H. (2007) Inflammatory processes in the aging mouse brain: Participation of dendritic cells and T-cells. Neurobiology of Aging, 28, 1507-1521.
[15] Baruch, K., Ron-Harel, N., Gal, H., et al. (2013) CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging. Proceedings of the National Academy of Sciences of the United States of America, 110, 2264-2269.
[16] Fee, D., Crumbaugh, A., Jacques, T., Herdrich, B., Sewell, D., et al. (2003) Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury. Journal of Neuroimmunology, 136, 54-66.
[17] Bodhankar, S., Chen, Y., Vandenbark, A.A., Murphy, S.J. and Offner, H. (2013) IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke. Metabolic Brain Disease, 28, 375-386.
[18] Mignini, F., Giovannetti, F., Cocchioni, M., Raponi, I. and Giorgio, I. (2012) Neuropeptide expression and T-lympho- cyte recruitment in facial nucleus after facial nerve axotomy. Journal of Craniofacial Surgery, 23, 1479-1483.
[19] Phillis, J.W., Horrocks, L.A. and Farooqui, A.A. (2006) Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: Their role and involvement in neurological disorders. Brain Research Reviews, 52, 201-243.
[20] Folkerth, R.D. (2005) Neuropathologic substrate of cerebral palsy. Journal of Child Neurology, 20, 940-949.
[21] Denes, A., Wilkinson, F., Bigger, B., Chu, M., Rothwell, N.J. and Allan, S.M. (2013) Central and haematopoietic interleukin-1 both contribute to ischaemic brain injury in mice. Disease Models & Mechanisms, 6, 1043-1048.
[22] Denes, A., Pinteaux, E., Rothwell, N.J. and Allan, S.M. (2011) Interleukin-1 and stroke: Biomarker, harbinger of da- mage, and therapeutic target. Cerebrovascular Diseases, 32, 517-527.
[23] Dinarello, C.A. (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood, 117, 3720- 3732.
[24] 钟照华, 李呼伦, 谷鸿喜, 赵文然, 田野, 李殿俊, 等 (2003) 人缺血脑组织中TNF-α和IL-1β的表达. 细胞与分子免疫学杂志, 19, 349-353.
[25] Emsley, H.C.A., Smith, C.J., Vail, A., Hopkins, S.J., Rothwell, N.J., et al. (2005) A randomised phase Ⅱ study of interleukin-1 receptor antagonist in acute stroke patients. Journal of Neurology, Neurosurgery & Psychiatry, 76, 1366- 1372.
[26] Xiong, X., Barreto, G.E., Xu, L., Ouyang, Y.B., Xie, X. and Giffard, R.G. (2011) Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia. Stroke, 42, 2026-2032.
[27] Abbas, A.K., Murphy, K.M. and Sher, A. (1996) Functional diversity of helper T lymphocytes. Nature, 383, 787-793.
[28] van Hogezand, R.A. and Verspaget, H.W. (1996) Selective immunomodulation in patients with inflammatory bowel disease—Future therapy or reality? The Netherlands Journal of Medicine, 48, 64-67.
[29] Dai, C., Fu, Y., Chen, S., Li, B., Yao, B., Liu, W.H., et al. (2013) Preparation and evaluation of a new releasable PEGylated tumor necrosis factor-α (TNF-α) conjugate for therapeutic application. Science China Life Sciences, 56, 51-58.
[30] Yang, G.Y., Gong, C., Qin, Z., Ye, W., Mao, Y. and Bertz, A.L. (1998) Inhibition of TNFalpha attenuates infarct volume and ICAM-1 expression in ischemic mouse brain. Neuroreport, 9, 2131-2134.
[31] Barone, F.C., Arvin, B., White, R.F., Miller, A., Webb, C.L., Willette, R.N., et al. (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke, 28, 1233-1244.
[32] Huang, L.W., Hsieh, B.S., Cheng, H.L., Hu, Y.C., Chang, W.T. and Chang, K.L. (2012) Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells. Toxicology and Applied Pharmacology, 258, 199-207.
[33] Beeton, C.A., Chatfield, D., Brooks, R.A. and Rushton, N. (2004) Circulating levels of interleukin-6 and its soluble receptor in patients with head injury and fracture. The Bone & Joint Journal, 86, 912-917.
[34] Swartz, K.R., Liu, F., Sewell, D., Schochet, T., Campbell, I., Sandor, M., et al. (2001) Interleukin-6 promotes post- traumatic healing in the central nervous system. Brain Research, 896, 86-95.
[35] Owens, T., Khorooshi, R., Wlodarczyk, A. and Asgari, N. (2014) Interferons in the central nervous system: A few instruments play many tunes. Glia, 62, 339-355.
[36] Veldhuis, B., Derksen, J.W., Floris, S., van der Meide, P.H., de Vries, H.E., Schepers, J., et al. (2003) Interferon-beta blocks infiltration of inflammatory cells and reduces infract volume after ischemic stroke in the rat. Journal of Cerebral Blood Flow & Metabolism, 23, 1029-1039.
[37] Choe, C.U., Lardong, K., Gelderblom, M., Lu-dewig, P., Leypoldt, F., Koch-Nolte, F., et al. (2011) CD38 exacerbates focal cytokine production, postischemic in-flammation and brain injury after focal cerebral ischemia. PLoS ONE, 6, e19046.
[38] Wang, Y., Ge, P. and Zhu, Y. (2013) TLR2 and TLR4 in the brain injury caused by cerebral ischemia and reperfusion. Mediators of Inflammation, 2013, Article ID: 124614.
[39] Vabulas, R.M., Ahmad-Nejad, P., da Costa, C., Miethke, T., Kirschning, C.J., Häcker, H., et al. (2001) Endocytosed HSP6os use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/ interleukin-1 receptor signaling pathway in innate immune cells. The Journal of Biological Chemistry, 276, 31332-31339.
[40] Zou, N., Ao, L., Cleveland Jr., J.C., Yang, X., Su, X., Cai, G.Y., et al. (2008) Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion. American Journal of Physiology, Heart and Circulatory Physiology, 294, H2805-H2813.
[41] Park, J.S., Gamboni-Robertson, F., He, Q., Svetkauskaite, D., Kim, J.Y., Strassheim, D., et al. (2006) High mobility group box 1 protein interacts with multiple Toll-like receptors. American Journal of Physiology, Cell Physiology, 290, 917-924.
[42] Ziegler, G., Harhausen, D., Schepers, C., Hoffmannb, O., Röhra, C., Prinz, V., et al. (2007) TLR2 has a detrimental role in mouse transient focal cerebral ischemia. Biochemical and Biophysical Research Communications, 359, 574- 579.
[43] Hyakkoku, K., Hamanaka, J., Tsuruma, K., Shimazawaa, M., Tanakab, H., Uematsu, S., et al. (2010) Toll-like receptor 4 (TLR4), but not TLR3 or TLR9, knock-out mice have neuroprotective effects against focal cerebral ischemia. Neuroscience, 171, 258-267.
[44] Deroide, N., Li, X., Lerouet, D., Van Vré, E., Baker, L., Harrison, J., et al. (2013) MFGE8 inhibits inflammasome-in- duced IL-1β production and limits postischemic cerebral injury. The Journal of Clinical Investigation, 123, 1176-1183.
[45] Noris, M. and Remuzzi, G. (2013) Overview of complement activation and regulation. Seminars in Nephrology, 33, 479-492.
[46] Carroll, M.C. and Isenman, D.E. (2012) Regulation of humoral immunity by complement. Immunity, 37, 199-207.
[47] Fluiter, K., Opperhuizen, A.L., Morgan, B.P., Baas, F. and Ramaglia, V. (2014) Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice. The Journal of Immunology, 192, 2339-2348.
[48] Brennan, F.H., Anderson, A.J., Taylor, S.M., Woodruff, T.M. and Ruitenberg, M.J. (2012) Complement activation in the injured central nervous system: Another dual-edged sword? Journal of Neuroinflammation, 9, 137.
[49] Woodruff, T.M., Ager, R.R., Tenner, A.J., Noakes, P.G. and Taylor, S.M. (2010) The role of the complement system and the activation fragment C5a in the central nervous system. NeuroMolecular Medicine, 12, 179-192.
[50] Veerhuis, R., Nielsen, H.M. and Tenner, A.J. (2011) Complement in the brain. Molecular Immunology, 48, 1592-1603.
[51] Ducruet, A.F., Zacharia, B.E., Sosunov, S.A., Gigante, P.R., Yeh, M.L., Gorski, J.W., et al. (2012) Complement inhibition promotes endogenous neurogenesis and sustained anti-inflammatory neuroprotection following reperfused stroke. PLoS ONE, 7, e38664.
[52] Bellander, B.M., Singhrao, S.K., Ohlsson, M., Mattsson, P. and Svens-son, M. (2001) Complement activation in the hu- man brain after traumatic head injury. Journal of Neurotrauma, 18, 1295-1311.
[53] Stahel, P.F., Morganti-Kossmann, M.C. and Kossmann, T. (1998) The role of the complement system in traumatic br- ain injury. Brain Research Reviews, 27, 243-256.
[54] Kossmann, T., Stahel, P.F., Morganti-Kossmann, M.C., Jones, J.L. and Barnum, S.R. (1997) Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury. Jo- urnal of Neuroimmunology, 73, 63-69.
[55] Bellander, B.M., von Holst, H., Fredman, P. and Svensson, M. (1996) Activation of the complement cascade and increase of clusterin in the brain following a cortical contusion in the adult rat. Journal of Neurosurgery, 85, 468-475.
[56] Hsiao, E.Y. (2013) Chapter nine, immune dysregulation in autism spectrum disorder. International Review of Neurobiology, 113, 269-302.
[57] Boutajangout, A. and Wisniewski, T. (2013) The innate immune system in Alzheimer’s disease. International Journal of Cell Biology, 2013, Article ID: 576383.
[58] Arroyo, D.S., Soria, J.A., Gaviglio, E.A., Rodriguez-Galan, M.C. and Iribarren, P. (2011) Toll-like receptors are key players in neurodegeneration. International Immunopharmacology, 11, 1415-1421.