Intermittent noxious stimulation following spinal cord contusion injury impairs locomotor recovery and reduces spinal brain-derived neurotrophic factor-tropomyosin-receptor kinase signaling in adult rats.
Intermittent noxious stimulation following spinal cord contusion injury impairs locomotor recovery and reduces spinal brain-derived neurotrophic factor-tropomyosin-receptor kinase signaling in adult rats.
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脊髓挫伤损伤后，间歇性有害刺激会损害运动的恢复，并减少脊柱脑源性的神经营养因子 - 霉菌素 - 肌球蛋白受体激素激酶信号传导。
DOI：
10.1016/j.neuroscience.2011.10.007
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发表时间：
2011-12-29
期刊：
影响因子：
3.3
通讯作者：
Grau, J. W.
中科院分区：
文献类型：
--
作者：
Garraway, S. M.;Turtle, J. D.;Huie, J. R.;Lee, K. H.;Hook, M. A.;Woller, S. A.;Grau, J. W.
完全横断或挫伤性脊髓损伤（SCI）后的间歇性伤害性刺激已被证明会产生几种短期和长期的负面后果。这些包括适应不良的脊柱可塑性，增强的机械性异常性疼痛和运动和膀胱功能的功能恢复受损。神经营养因子，脑源性神经营养因子（BDNF）已被证明在适应性可塑性中发挥重要作用，并在SCI后恢复功能。这表明，休克的负面行为效应最有可能与BDNF脊髓水平的相应变化有关。在这项研究中，我们研究了伤害性刺激的细胞效应，在挫伤的成年大鼠集中在BDNF，其受体，TrkB，和随后的下游信号系统。目的是确定刺激的行为效应是否与损伤后初期诱导的伴随细胞变化相关。采用定量RT-PCR和蛋白质印迹法检测挫伤受试者尾部间歇性伤害性休克后1 h、24 h和7 d BDNF、TrkB及其下游信号蛋白CAMK Ⅱ和ERK 1/2的mRNA和/或蛋白水平的变化。此外，在损伤后第一周每天评估运动功能（BBB评分）的恢复。结果表明，虽然伤害性刺激在1小时时未能诱导基因表达的任何变化，但在24小时时显著降低了BDNF、TrkB、ERK 2和CAMK II的表达。一般来说，基因表达的变化在空间上定位于脊髓背侧。此外，运动恢复受损休克。还提供的证据表明，休克参与神经元回路，而不会对24小时的神经元存活产生任何负面影响。这些结果表明，SCI后的伤害性活动降低了BDNF和TrkB水平，这可能显着有助于减少功能恢复。
Intermittent nociceptive stimulation following a complete transection or contused spinal cord injury (SCI) has been shown to exert several short and long lasting negative consequences. These include maladaptive spinal plasticity, enhanced mechanical allodynia and impaired functional recovery of locomotor and bladder functions. The neurotrophin, brain derived neurotrophic factor (BDNF) has been shown to play an important role in adaptive plasticity and also to restore functions following SCI. This suggests that the negative behavioral effects of shock are most likely related to corresponding changes in BDNF spinal levels. In this study we investigated the cellular effects of nociceptive stimulation in contused adult rats focusing on BDNF, its receptor, TrkB, and the subsequent downstream signaling system. The goal was to determine whether the behavioral effect of stimulation is associated with concomitant cellular changes induced during the initial post-injury period. Quantitative RT-PCR and western blotting were used to assess changes in the mRNA and/or protein levels of BDNF, TrkB and the downstream signaling proteins CAMKII and ERK1/2 at 1 hour, 24 hours and 7 days following administration of intermittent noxious shock to the tail of contused subjects. In addition, recovery of locomotor function (BBB score) was assessed daily for the first week post injury. The results showed that, while nociceptive stimulation failed to induce any changes in gene expression at 1 hour, it significantly reduced the expression of BDNF, TrkB, ERK2 and CAMKII, at 24 hours. In general, changes in gene expression were spatially localized to the dorsal spinal cord. In addition, locomotor recovery was impaired by shock. Evidence is also provided suggesting that shock engages a neuronal circuitry without having any negative effects on neuronal survival at 24 hours. These results suggest that nociceptive activity following SCI decreases BDNF and TrkB levels, which may significantly contribute to diminished functional recovery.
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影响因子：
1.9
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Grau, JW;Barstow, DG;Joynes, RL
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