THE EFFECT OF MECHANICAL STRAIN OR HYPOXIA ON CELL DEATH IN SUBPOPULATIONS OF RAT DORSAL ROOT GANGLION NEURONS IN VITRO
THE EFFECT OF MECHANICAL STRAIN OR HYPOXIA ON CELL DEATH IN SUBPOPULATIONS OF RAT DORSAL ROOT GANGLION NEURONS IN VITRO
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DOI：
10.1016/j.neuroscience.2010.07.009
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发表时间：
2010-12-01
期刊：
影响因子：
3.3
通讯作者：
Priestley, J. V.
中科院分区：
文献类型：
--
作者：
Gladman, S. J.;Ward, R. E.;Priestley, J. V.
脊髓神经及其相关的背根神经节 (DRG) 细胞可能会遭受与椎间盘突出、椎管狭窄和脊柱创伤等病理相关的机械变形和缺氧。关于成人 DRG 神经元对此类应激源的反应的信息非常有限。在本研究中，我们使用体外方法来检查成人 DRG 细胞对 (a) 机械、缺氧和综合损伤的反应，以及 (b) 比较对伤害感受和非伤害的影响。伤害性神经元以及非神经元细胞 机械损伤（20% 拉伸应变）导致显着的神经元细胞死亡（通过乙锭同二美 1 标记评估），其与应变持续时间（5 分钟、1 小时、6 小时或 18 小时）成正比。缺氧（2% O-2，持续 24 小时）也促进 DRG 神经元死亡，当机械应变和缺氧结合时，这种死亡进一步增强 机械应变和缺氧均显着减少相反，非神经元细胞的死亡仅因缺氧而增加，而不会因机械应变而增加 非伤害性（神经丝，NF-200 免疫反应性）和伤害性（降钙素基因相关肽 CGRP 免疫反应性）神经元对机械损伤或缺氧的总细胞死亡相似，但 CGRP 中的细胞凋亡（通过激活的 caspase 3 免疫染色评估）显着高于 NF-200 神经元令人惊讶的是，非肽能伤害感受器（由加纳单叶 IB4 凝集素结合鉴定）的细胞死亡在对照培养物中已经很高，并且不会因机械拉伸或缺氧而进一步增加。这些结果提供了有关成人 DRG 亚群对缺氧和机械应变的反应的详细信息，并描述了可用于筛选潜在神经保护剂的体外模型 (C) 2010 IBRO 由 Elsevier Ltd 出版保留所有权利
Spinal nerves and their associated dorsal root ganglion (DRG) cells can be subject to mechanical deformation and hypoxia associated with pathology such as disc herniation, spinal stenosis and spine trauma There is very limited information on the response of adult DRG neurons to such stressors In this study we used an in vitro approach to examine the response of adult DRG cells to (a) mechanical, hypoxic, and combined injuries, and (b) to compare the effects on injury on nociceptive and non nociceptive neurons, as well as on non-neuronal cells Mechanical injury (20% tensile strain) led to significant neuronal cell death (assessed by ethidium homodimei 1 labelling), which was proportional to strain duration (5 min, 1 h 6 h or 18 h) Hypoxia (2% O-2 for 24 h) also promoted death of DRG neurons, and was further enhanced when mechanical strain and hypoxia were combined Both mechanical strain and hypoxia significantly de creased the maximum neurite length Conversely, death of non neuronal cells was only increased by hypoxia and not by mechanical strain Total cell death in response to mechanical injury or hypoxia was similar in both non nociceptive (neurofilament, NF-200 immunoreactive) and nociceptive (calcitonun gene related peptide CGRP immunoreactive) neurons but apoptosis (assessed by activated caspase 3 immuno staining) was significantly higher in CGRP than NF-200 neurons Surprisingly, cell death of non peptidergic nociceptors (identified by Griffonia simplicifolia IB4 lectin binding) was already high in control cultures and was not increased further by either mechanical stretch or hypoxia These results provide detailed information on the response of adult DRG subpopulations to hypoxia and mechanical strain, and de scribe in vitro models that could be useful for screening potential neuroprotective agents (C) 2010 IBRO Published by Elsevier Ltd All rights reserved