Yong V W, Giuliani F, Xue M, Bar-Or A, Metz L M
Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
Neurology. 2007 May 29;68(22 Suppl 3):S32-7; discussion S43-54. doi: 10.1212/01.wnl.0000275230.20635.72.
Activated T cells, particularly those of the T-helper (Th) 1 subset, have the capacity to kill neurons. Strategies for preventing such damage may include deviation of activated T cells into the Th2 subset (e.g., via use of glatiramer acetate), alteration of functional properties of Th1 cells (e.g., through use of interferon [INF]-beta or IV immunoglobulin), and inhibition of activated cell migration into the CNS (e.g., by employing INF-beta or natalizumab). Matrix metalloproteinase-9 (MMP-9) also causes neuron death in neurotoxicity models, and examination of medications with MMP inhibitory activity indicates that minocycline is capable of preventing such damage. Minocycline also has other properties relevant to conferring neuroprotection, such as inhibition of microglial activity and apoptosis pathways. In a small pilot study in patients with relapsing-remitting multiple sclerosis, minocycline treatment produced favorable outcomes in terms of gadolinium-enhancing lesions and clinical course. Further studies are needed to establish whether experimental neuroprotection strategies involving these mechanisms may be translated into preventing neurodegeneration in multiple sclerosis.
活化的T细胞，尤其是辅助性T细胞（Th）1亚群的细胞，具有杀伤神经元的能力。预防此类损伤的策略可能包括将活化的T细胞偏向Th2亚群（例如，通过使用醋酸格拉替雷）、改变Th1细胞的功能特性（例如，通过使用干扰素[INF]-β或静脉注射免疫球蛋白），以及抑制活化细胞向中枢神经系统的迁移（例如，通过使用INF-β或那他珠单抗）。基质金属蛋白酶-9（MMP-9）在神经毒性模型中也会导致神经元死亡，对具有MMP抑制活性的药物进行研究表明，米诺环素能够预防此类损伤。米诺环素还具有其他与赋予神经保护作用相关的特性，如抑制小胶质细胞活性和凋亡途径。在一项针对复发缓解型多发性硬化症患者的小型初步研究中，米诺环素治疗在钆增强病灶和临床病程方面产生了良好的结果。需要进一步研究来确定涉及这些机制的实验性神经保护策略是否可以转化为预防多发性硬化症中的神经退行性变。
