An adult rat spinal cord contusion model of sensory axon degeneration: The estrus cycle or a preconditioning lesion do not affect outcome
An adult rat spinal cord contusion model of sensory axon degeneration: The estrus cycle or a preconditioning lesion do not affect outcome
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DOI：
10.1089/neu.2005.22.415
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发表时间：
2005-04-01
影响因子：
4.2
通讯作者：
Hagg, T
中科院分区：
文献类型：
--
作者：
Baker, KA;Hagg, T
急性脊髓损伤的治疗策略是减少轴突的进行性退化和与其靶点的脱离。在这里，我们描述了一个模型来评估成年雌性Spraogue-Dawley大鼠脊髓挫伤后到延髓核的上升感觉投射的退化。幼年大鼠坐骨神经霍乱毒素B(CTB)标记结果显示，注射后3d松弛核终末纤维得到有效标记，1d后可见大量快速运输纤维。挫伤后7天，CTB标记的终末纤维面积与冲击力的增加呈负相关。约150kdyn(kdyn或0.15x10(-3)牛顿)的中度脊柱挫伤导致纤维面积减少至40%，这将使保护以及有害药物和损伤后机制的识别成为可能。据报道，坐骨神经的预适应损伤可以促进感觉轴突的生长，但不影响薄束核中的终末纤维区域。雌激素和黄体酮在不同的系统中具有保护作用，因此当使用女性时，可能会影响实验结果。然而，挫伤时或伤后动情周期的不同阶段并不影响挫伤的结局，这表明雌性大鼠可以不考虑动情周期。该模型可以很容易地用于评价药物对感觉神经轴突的保护及其退变的病理生理机制。
A therapeutic strategy for acute spinal cord injury would be to reduce the progressive degeneration and disconnection of axons from their targets. Here, we describe a model to evaluate degeneration of the ascending sensory projections to the nuclei in the medulla following graded spinal cord contusions in adult female Sprague-Dawley rats. Cholera toxin B (CTB) labeling from the sciatic nerve of naive rats revealed effective labeling of the terminal fibers in the gracile nucleus at 3 days post-injection and a subpopulation of rapidly transporting fibers after 1 day. Seven days after contusions using the Infinite Horizon impactor the area of CTB-labeled terminal fibers had a negative correlation with increasing impact force. Moderate spinal contusions of around 150 kilodyne (kdyn or 0.15 x 10(-3) newton) caused a reduction to 40% in the fiber area which will enable the identification of protective as well as detrimental drugs and post-injury mechanisms. A preconditioning injury of the sciatic nerve reportedly can enhance growth of sensory axons but did not affect the terminal fiber area in the gracile nucleus. Estrogen and progesterone are protective in various systems and could therefore influence experimental outcomes when using females. However, the phase of the estrus cycle at the time of contusion or during the post-injury time did not affect the outcome of the contusion, indicating that female rats may be used without consideration of the estrus cycle. This model can readily be used to evaluate pharmacological agents for protection of sensory axons and pathophysiological mechanisms of their degeneration.