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A rat model for chronic spinal nerve root compression

机译:慢性脊髓神经根压迫的大鼠模型

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Objectives The pathophysiology of radiculopathy associated with lumbar spinal stenosis and lumbar disc herniation is incompletely understood. The goal of the present study was to establish a chronic spinal nerve root compression model that can mimic lumbar disc herniation or spinal stenosis using silicone tube compression. We also try to link the pathology changes of damaged nerve root with the reaction of microglia in spinal cord in same rat at different time points.MethodsThirty rats were used in this study. The L5 nerve roots (dorsal and ventral) were exposed by hemilaminectomy; the diameter of the L5 nerve root was measured at the 2?mm proximal from the dorsal root ganglia. The dorsal and ventral nerve roots of L5 were compressed using a silicone tube, and the sham group was only exposed dorsal and ventral roots of L5. Five rats from the sham group were perfused at 8?days after surgery, and 25 rats from the model groups were perfused at 3, 8, 12, 45?days, and 5?months after surgery, each model group was composed of 5 rats according to the time point. The L5 spinal cord segments and nerve root that compressed by silicone tube were harvested from the same rat. Microglia and neuron in the spinal cord were stained by immunohistochemistry, and the nerve root was shown by electron microscope.ResultsIn sham-operated rat, the arrangement of axon and myelin sheath is normal, the ventral root is mainly composed of large axon (6?μm) and it is composed of 46.3?% of all the axons of the ventral root; the average myelin thickness of large axon is 1.86?μm; the dorsal root is mainly composed of medium (2–3.9 or 4–5.9?μm) axons and they are composed of 79.1?% of all the axons of the dorsal root; the average myelin thickness of this category is 0.94 or 1.55?μm. The average myelin thickness of large axon in ventral root reduced to 0.97 and 1.19?μm from more than 1.86?μm after compression for 3 and 8?days separately. Most of myelin sheath disappeared after 12?days of compression; the myelin sheath was partly restored at 45?days after compression which the myelin sheath thickness of large axons in ventral root was 0.47?μm. The medium category in dorsal root reduced to 0.59 or 0.72?μm from 0.94?μm, and 1.55?μm after compression for 3?days (p??0.05 to p??0.0001). The medium category axon in dorsal root is also 0.47?μm after compression for 45?days (p?≤?0.0001). The myelin sheath was almost totally restored at the 5?months of compression; the myelin sheath thickness returned to normal and the axons were intact in structure under EM. The number of Iba1-positive microglia increased by 18.69, 40.44, and 18.49?% after compression for 3, 8, and 12?days separately in the ipsilateral dorsal horn and 21.26, 32.15, 22.87?% in ventral horns, and the activation of microglia was also prominent in contralateral sides of the dorsal and ventral horn at 8?days time point. The microglia cell reconverted to resting status after compression for 45?days or 5?months.ConclusionThe chronic spinal nerve root compression with silicone tube produces a recoverable damage to nerve root, which produces recoverable microglial activation in the spinal cord. These results demonstrated that the chronic spinal nerve root compression with silicone tube could mimic the pathological changes of lumbar spinal stenosis or lumbar disc herniation...
机译:目的对与腰椎管狭窄和腰椎间盘突出症相关的神经根病的病理生理学尚未完全了解。本研究的目的是建立一个慢性脊髓神经根压迫模型,该模型可使用硅胶管压迫来模拟腰椎间盘突出或椎管狭窄。我们还试图将损伤的神经根的病理变化与同一只大鼠在不同时间点的脊髓小胶质细胞反应联系起来。方法采用30只大鼠。通过半椎板切除术暴露L5神经根(背侧和腹侧); L5神经根的直径在背根神经节的近端2?mm处测量。用硅胶管压迫L5的背侧和腹侧神经根,假手术组仅暴露L5的背侧和腹侧根部。假手术组在术后第8天灌注了5只大鼠,模型组在手术后第3、8、12、45天和第5个月分别灌注了25只大鼠,每个模型组由5只大鼠组成根据时间点。取自同一只大鼠的L5脊髓节段和硅胶管压迫的神经根。免疫组化染色显示脊髓小胶质细胞和神经元,电镜观察神经根。结果假手术组大鼠轴突和髓鞘排列正常,腹侧根主要由大轴突组成(> 6)。 (μm),由腹根所有轴突的46.3%组成;大轴突的平均髓鞘厚度为1.86?μm。背根主要由中等(2–3.9?或4–5.9?m)轴突组成,它们占背根所有轴突的79.1%。该类别的平均髓磷脂厚度为0.94或1.55?μm。腹侧根大轴突的平均髓鞘厚度从分别压迫3天和8天后的1.86?μm降至0.97和1.19?m。压迫12天后大部分髓鞘消失;加压后45天,髓鞘鞘部分恢复,腹侧大轴突的髓鞘鞘厚度为0.47μm。背根中的介质类别从0.94μm减小到0.59或0.72μm,压缩3天后减小到1.55μm(p <0.05到p <0.0001)。压迫45天后,背根的中型轴突也为0.47?μm(p?≤?0.0001)。在压迫的5个月时,髓鞘几乎完全恢复。 EM下髓鞘厚度恢复正常,轴突结构完整。在同侧背角分别压迫3、8和12天后,Iba1阳性小胶质细胞的数量分别增加了18.69、40.44和18.49%,在腹角部和激活的腹侧角分别为21.26、32.15、22.87%在8天的时间点,小胶质细胞在背角和腹角的对侧也很明显。结论小胶质细胞在受压45天或5个月后恢复到静止状态。结论硅胶管对慢性脊髓神经根的压迫对神经根产生可恢复的损伤,从而在脊髓中产生可恢复的小胶质细胞活化。这些结果表明,硅胶管对慢性脊髓神经根的压迫可以模拟腰椎管狭窄或腰椎间盘突出症的病理变化。

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