Dorsal root ganglion neurons recapitulate the traumatic axonal injury of CNS neurons in response to a rapid stretch in vitro.
Dorsal root ganglion neurons recapitulate the traumatic axonal injury of CNS neurons in response to a rapid stretch in vitro.
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DOI：
10.3389/fncel.2023.1111403
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发表时间：
2023
影响因子：
5.3
通讯作者：
Pfister, Bryan J.
中科院分区：
文献类型：
--
作者：
Adams, Alexandra A.;Li, Ying;Kim, Haesun A.;Pfister, Bryan J.
关键词：
简介：创伤性脑损伤（TBI）的体外模型通常使用从中枢神经系统分离的神经元。然而，原代皮质培养的局限性可能会对复制与闭合性头部 TBI 相关的神经元损伤的某些方面提出挑战。 TBI 中机械损伤引起的轴突变性的已知机制在许多方面与退行性疾病、缺血和脊髓损伤相似。因此，体外拉伸损伤后导致分离的皮质轴突轴突变性的机制可能与来自不同神经元类型的受损轴突相同。背根神经节神经元（DRGN）是另一种神经元来源，可以克服目前的一些限制，包括在培养物中长时间保持健康、能够从成体来源中分离出来以及在体外有髓鞘化。方法：本研究旨在描述皮质轴突和 DRGN 轴突对 TBI 相关机械拉伸损伤的不同反应。使用创伤性轴突拉伸损伤的体外模型，皮质和 DRGN 神经元在中度拉伸（40% 应变）和重度拉伸（60% 应变）下受伤，并测量轴突形态和钙稳态的急性变化。结果：DRGN 和皮质轴突在严重损伤时立即形成波动，在初次损伤后 20 分钟内经历相似的伸长和恢复，并且在损伤后的前 24 小时内具有相似的退化模式。此外，两种类型的轴突在中度和重度损伤后都经历了相当程度的钙内流，这是通过在皮质神经元中使用河豚毒素和在 DRGN 中使用利多卡因进行预处理来预防的。与皮质轴突类似，拉伸损伤也会导致 DRGN 轴突中钠通道的钙激活蛋白水解，而利多卡因或蛋白酶抑制剂可防止这种情况的发生。讨论：这些发现表明 DRGN 轴突具有皮质神经元对快速拉伸损伤的早期反应以及相关的继发性损伤机制。 DRGN 体外 TBI 模型的实用性可能允许未来的研究探索有髓神经元和成体神经元的 TBI 损伤进展。
Introduction: In vitro models of traumatic brain injury (TBI) commonly use neurons isolated from the central nervous system. Limitations with primary cortical cultures, however, can pose challenges to replicating some aspects of neuronal injury associated with closed head TBI. The known mechanisms of axonal degeneration from mechanical injury in TBI are in many ways similar to degenerative disease, ischemia, and spinal cord injury. It is therefore possible that the mechanisms that result in axonal degeneration in isolated cortical axons after in vitro stretch injury are shared with injured axons from different neuronal types. Dorsal root ganglia neurons (DRGN) are another neuronal source that may overcome some current limitations including remaining healthy in culture for long periods of time, ability to be isolated from adult sources, and myelinated in vitro. Methods: The current study sought to characterize the differential responses between cortical and DRGN axons to mechanical stretch injury associated with TBI. Using an in vitro model of traumatic axonal stretch injury, cortical and DRGN neurons were injured at a moderate (40% strain) and severe stretch (60% strain) and acute alterations in axonal morphology and calcium homeostasis were measured. Results: DRGN and cortical axons immediately form undulations in response to severe injury, experience similar elongation and recovery within 20 min after the initial injury, and had a similar pattern of degeneration over the first 24 h after injury. Additionally, both types of axons experienced comparable degrees of calcium influx after both moderate and severe injury that was prevented through pre-treatment with tetrodotoxin in cortical neurons and lidocaine in DRGNs. Similar to cortical axons, stretch injury also causes calcium activated proteolysis of sodium channel in DRGN axons that is prevented by treatment with lidocaine or protease inhibitors. Discussion: These findings suggest that DRGN axons share the early response of cortical neurons to a rapid stretch injury and the associated secondary injury mechanisms. The utility of a DRGN in vitro TBI model may allow future studies to explore TBI injury progression in myelinated and adult neurons.
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影响因子：
3.5
作者：
Ho, Cojen;O'Leary, Michael E.
通讯作者：
O'Leary, Michael E.
影响因子：
4.2
作者：
Lea, PM;Custer, SJ;Faden, AI
通讯作者：
Faden, AI
DOI：
10.1115/1.2895464
发表时间：
1993-02-01
影响因子：
1.7
作者：
GALBRAITH, JA;THIBAULT, LE;MATTESON, DR
通讯作者：
MATTESON, DR
影响因子：
3.8
作者：
LaPlaca, MC;Thibault, LE
通讯作者：
Thibault, LE
影响因子：
4.1
作者：
Huang, Jason H.;Cullen, D. Kacy;Smith, Douglas H.
通讯作者：
Smith, Douglas H.