Translational strategies in peripheral neuroinflammation and neurovascular repair.
Translational strategies in peripheral neuroinflammation and neurovascular repair.
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DOI：
10.2478/s13380-012-0039-4
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发表时间：
2012-12-01
影响因子：
2.1
通讯作者：
Ubogu EE
中科院分区：
文献类型：
--
作者：
Ubogu EE
目前针对周围神经免疫介导的炎症性疾病的治疗方法是非特异性的，并且部分有效。轴突变性或损伤后的周围神经再生效果不佳，目前的治疗重点是调节潜在病因并治疗神经性疼痛和虚弱等后果。尽管在理解周围神经炎症以及轴突变性和再生机制方面取得了重大进展，但转化为治疗这些疾病的有效新药的情况仍然有限。该领域的一个主要限制是缺乏可靠的疾病模型或研究工具来模拟这些人类状况的一些关键基本特征。周围神经再生的一个相对被忽视的方面是恢复正常功能所需的稳态微环境所需的神经血管修复。我们分别以格林-巴利综合征（GBS）和慢性炎症性脱髓鞘性多发性神经根神经病（CIDP）作为人类急性和慢性免疫介导的周围神经炎症性疾病的例子，在代表性小鼠模型中进行了详细的研究，以证明人类疾病的基本特征。这些模型是使用适用于受影响患者的现实结果测量来开发和测试治疗策略的重要工具。使用神经内膜微血管衍生的内皮细胞建立人血神经屏障的体外模型，可深入了解与周围神经炎症相关的促炎性白细胞-内皮细胞相互作用，以及损伤后恢复周围神经功能所需的血管增殖、血管生成、重塑和紧密连接专门化所需的潜在介质和信号通路。这篇综述讨论了我们在转化周围神经生物学方面取得的进展以及我们未来的方向。
Current therapies for immune-mediated inflammatory disorders in peripheral nerves are non-specific, and partly efficacious. Peripheral nerve regeneration following axonal degeneration or injury is suboptimal, with current therapies focused on modulating the underlying etiology and treating the consequences, such as neuropathic pain and weakness. Despite significant advances in understanding mechanisms of peripheral nerve inflammation, as well as axonal degeneration and regeneration, there has been limited translation into effective new drugs for these disorders. A major limitation in the field has been the unavailability of reliable disease models or research tools that mimic some key essential features of these human conditions. A relatively overlooked aspect of peripheral nerve regeneration has been neurovascular repair required to restore the homeostatic microenvironment necessary for normal function. Using Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as examples of human acute and chronic immune-mediated peripheral neuroinflammatory disorders respectively, we have performed detailed studies in representative mouse models to demonstrate essential features of the human disorders. These models are important tools to develop and test treatment strategies using realistic outcomes measures applicable to affected patients. In vitro models of the human blood-nerve barrier using endothelial cells derived by endoneurial microvessels provide insights into pro-inflammatory leukocyte-endothelial cell interactions relevant to peripheral neuroinflammation, as well as potential mediators and signaling pathways required for vascular proliferation, angiogenesis, remodeling and tight junction specialization necessary to restore peripheral nerve function following injury. This review discusses the progress we are making in translational peripheral neurobiology and our future directions.
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影响因子：
8.2
作者：
MALIK, RA;NEWRICK, PG;WARD, JD
通讯作者：
WARD, JD
影响因子：
14.5
作者：
Kieseier, BC;Tani, M;Hartung, HP
通讯作者：
Hartung, HP
影响因子：
1.7
作者：
Hammarberg, H;Piehl, F;Fried, K
通讯作者：
Fried, K
DOI：
10.1084/jem.20082113
发表时间：
2009-03-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Louvet C;Kabre BG;Davini DW;Martinier N;Su MA;DeVoss JJ;Rosenthal WL;Anderson MS;Bour-Jordan H;Bluestone JA
通讯作者：
Bluestone JA
影响因子：
11.2
作者：
GIANNINI, C;DYCK, PJ
通讯作者：
DYCK, PJ