Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats.
Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats.
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DOI：
10.1016/j.expneurol.2011.10.010
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发表时间：
2012-04
影响因子：
5.3
通讯作者：
Hulsebosch, Claire E.
中科院分区：
文献类型：
--
作者：
Gwak, Young S.;Kang, Jonghoon;Unabia, Geda C.;Hulsebosch, Claire E.
在脊髓中，神经元和神经胶质细胞积极相互作用并促进神经功能。令人惊讶的是，这两种细胞类型具有相似的受体，转运蛋白和离子通道，也产生相似的神经递质和细胞因子。神经解剖学和神经化学的相似性协同工作，以维持正常脊髓的生理稳态。然而，在创伤或疾病状态下，脊髓胶质细胞被激活，背角神经元变得过度兴奋，有助于敏化神经元-胶质细胞回路。适应不良的脊髓回路直接影响突触兴奋性，包括细胞内下游级联的激活，其导致背角神经元中的诱发和自发活动增强，结果发展出异常疼痛综合征。最近的文献报道，脊髓损伤产生胶质细胞激活的背角;然而，大多数神经胶质细胞激活的SCI后的研究集中在短暂的和/或急性的时间点，从几个小时到一个月，和周围的病变部位，几毫米的头和尾的病变部位。此外，胸脊髓损伤产生星形胶质细胞和小胶质细胞的活化，其有助于背角神经元过度兴奋和远离脊髓中的病变的水平上、水平上和水平下节段中的中枢神经性疼痛。胶质细胞活化的细胞和分子事件不是一个简单的事件，而是SCI后几种神经化学和神经生理学变化相结合的结果。SCI后离子失衡、神经炎症和细胞周期蛋白的改变是导致胶质细胞活化的神经解剖学和神经化学变化的主要组成部分。更重要的是，SCI诱导的谷氨酸、促炎性细胞因子、ATP、活性氧（ROS）和神经营养因子的释放通过其自身的受体和通道触发突触后神经元和神经胶质细胞的激活，这反过来有助于神经元-神经元和神经元-神经胶质细胞的相互作用以及小胶质细胞-星形胶质细胞的相互作用。然而，还没有对SCI后神经胶质的时空激活进行系统的综述。在这篇综述中，我们描述了胶质细胞激活的时间和区域依赖性，并描述了各种SCI大鼠模型的激活机制。这些数据被放置在神经胶质细胞激活机制和慢性疼痛状态的更广泛的背景下。我们的工作在SCI模型中的其他工作的背景下表明，功能失调的神经胶质，一种称为“神经胶质病”的病症，是导致神经病理性疼痛的潜在细胞机制的关键贡献者。
In the spinal cord, neurons and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop. Recent literature reported that spinal cord injury produces glial activation in the dorsal horn; however, the majority of glial activation studies after SCI have focused on transient and/or acute time points, from a few hours to one month, and peri-lesion sites, a few millimeters rostral and caudal to the lesion site. In addition, thoracic spinal cord injury produces activation of astrocytes and microglia that contributes to dorsal horn neuronal hyperexcitability and central neuropathic pain in above-level, at-level and below-level segments remote from the lesion in the spinal cord. The cellular and molecular events of glial activation are not a simple event, rather it is the consequence of a combination of several neurochemical and neurophysiological changes following SCI. The ionic imbalances, neuroinflammation and alterations of cell cycle proteins after SCI are predominant components for neuroanatomical and neurochemical changes that result in glial activation. More importantly, SCI induced release of glutamate, proinfloammatory cytokines, ATP, reactive oxygen species (ROS) and neurotrophic factors trigger activation of postsynaptic neurons and glial cells via their own receptors and channels that, in turn, contribute to neuronal-neuronal and neuronal-glial interaction as well as microglia-astrocytic interactions. However, a systematic review of temporal and spatial glial activation following SCI has not been done. In this review, we describe time and regional dependence of glial activation and describe activation mechanisms in various SCI models in rats. These data are placed in the broader context of glial activation mechanisms and chronic pain states. Our work in the context of work by others in SCI models demonstrate that dysfunctional glia, a condition called “gliopathy”, are key contributors in the underlying cellular mechanisms contributing to neuropathic pain.
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影响因子：
5.3
作者：
Colburn, RW;Rickman, AJ;DeLeo, JA
通讯作者：
DeLeo, JA
影响因子：
4.2
作者：
Baldwin, SA;Broderick, R;Scheff, SW
通讯作者：
Scheff, SW
影响因子：
5
作者：
Bastos, Leandro Francisco S.;Merlo, Leonardo A.;Coelho, Marcio M.
通讯作者：
Coelho, Marcio M.
影响因子：
7.4
作者：
Carlton SM;Du J;Tan HY;Nesic O;Hargett GL;Bopp AC;Yamani A;Lin Q;Willis WD;Hulsebosch CE
通讯作者：
Hulsebosch CE
影响因子：
6.2
作者：
BALLESTAS, ME;BENVENISTE, EN
通讯作者：
BENVENISTE, EN