The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats

The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats
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DOI:
10.1111/j.1460-9568.2006.05284.x
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发表时间:
2007-01-01
影响因子:
3.4
通讯作者:
Priestley, J. V.
Priestley, J. V.
中科院分区:
医学3区
文献类型:
--
作者:
Huang, W. L.;George, K. J.;Priestley, J. V.

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使用挫伤(冲击)损伤范式对脊髓损伤的研究表明,神经元死亡是一个急性事件,主要在24小时内结束。然而,尽管压迫是自然脊髓损伤的关键组成部分,但对压迫损伤后细胞死亡的了解却少得多。因此,我们使用神经元核(NeuN)免疫染色来检测成年大鼠静态压缩损伤后神经元丢失的时空模式。使用三维重建来显示损伤的全部影响。通过NeuN免疫染色评估,损伤中心的神经元损失在第1天达到44%,但在第3天和第1个月增加到73%和81%。距震中5毫米的吻侧和尾侧也有神经元丢失,但直到3天才明显。NeuN损失在腹侧角和中间灰质中最大,而侧背角相对较少。损伤后形成囊腔,但在4周后才明显,且体积较小。与缓慢的神经元损失相比,压缩损伤也引起了神经元中激活转录因子-3 (ATF3)和激活c-Jun的短暂表达。ATF3表达在第3天达到高峰,第7天下降。我们对压缩性损伤的时空分析表明,与挫伤损伤相比,压缩性损伤的神经元损失要长得多,并强调了神经保护策略的潜力。这项研究也是ATF3参与脊髓损伤的第一个迹象。
Studies of spinal cord injury using contusion (impact) injury paradigms have shown that neuronal death is an acute event that is largely over within 24 h. However, much less is known about cell death following compression injury, despite compression being a key component of natural spinal injuries. We have therefore used neuronal nuclei (NeuN) immunostaining to examine the spatiotemporal pattern of neuronal loss after static compression injury in adult rats. 3D reconstruction was used to reveal the full effect of the injury. Neuronal loss at the injury epicentre, assessed by NeuN immunostaining, amounted to 44% at 1 day but increased to 73% at 3 days and 81% at 1 month. Neuronal loss was also seen 5 mm rostral and caudal to the epicentre, but was not significant until 3 days. NeuN loss was greatest in the ventral horns and in the intermediate grey matter, with the lateral dorsal horns relatively spared. Cystic cavities formed after injury, but were not evident until 4 weeks and were small in size. In contrast to the slow profile of neuronal loss, the compression injury also evoked a transient expression of activating transcription factor-3 (ATF3) and activated c-Jun in neurons. ATF3 expression peaked at 3 days and declined at 7 days. Our spatiotemporal analysis of compression injury shows that neuronal loss is much more protracted than in contusion injury, and highlights the potential for neuroprotective strategies. This study is also the first indication of ATF3 involvement in spinal cord injury.