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两种成年大鼠神经根撕脱伤模型的组织学比较分析。

A comparative histological analysis of two models of nerve root avulsion injury in the adult rat.

机构信息

Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK.

出版信息

Neuropathol Appl Neurobiol. 2011 Oct;37(6):613-32. doi: 10.1111/j.1365-2990.2011.01176.x.

Abstract

AIMS

This study has investigated the reliability of the artificial surgical model dorsal root rhizotomy (DRR), to the surgical tearing of the roots, avulsion, that occurs clinically. Root avulsion of the limb nerves is common in high-impact motor vehicle accidents and results in paraesthesia, paralysis and intractable pain. Limited treatment options are largely due to a lack of basic research on underlying mechanisms, and few animal models. We assess this limitation by histologically assessing the spatial and temporal injury profile of dorsal root avulsion (DRA) and DRR within the spinal cord.

METHODS

Rats underwent DRR, DRA or sham surgery to the L3-L6 dorsal roots unilaterally. At 1, 2, 14, and 28 days post injury, immunohistochemical density staining was used to characterize the progression of spinal cord trauma. Neuronal (NeuN) and vascular degeneration (RECA-1), inflammatory infiltrate (ED1, anti-neutrophil), gliosis (Iba1, GFAP) and apoptosis (TUNEL) were assessed.

RESULTS

Unilateral DRA produced a prolonged and bilateral glial and inflammatory response, and vascular degeneration compared to transient and unilateral effects after DRR. Transsynaptic neurodegeneration after DRA was greater than after DRR, and progressed across 28 days coinciding with gliosis and macrophage infiltration.

CONCLUSIONS

Rhizotomy leads to a milder representation of the spinal cord trauma that occurs after 'true' avulsion injury. We recommend DRA be used in the future to more reliably model clinical avulsion injury. Avulsion is an injury with a chronic profile of degenerative and inflammatory progression, and this theoretically provides a window of clinical therapeutic opportunity in treatment of secondary trauma progression.

摘要

目的

本研究旨在调查人工外科模型背根切断术(DRR)的可靠性,以模拟临床上发生的神经根撕脱。肢体神经的神经根撕脱在高冲击力机动车事故中很常见,导致感觉异常、瘫痪和难治性疼痛。由于对潜在机制的基础研究有限,以及很少有动物模型,因此治疗选择有限。我们通过组织学评估脊髓内背根撕脱(DRA)和 DRR 的空间和时间损伤特征来评估这一局限性。

方法

大鼠单侧接受 DRR、DRA 或假手术。在损伤后 1、2、14 和 28 天,用免疫组织化学密度染色来描述脊髓损伤的进展。评估神经元(NeuN)和血管退变(RECA-1)、炎症浸润(ED1、抗中性粒细胞)、神经胶质增生(Iba1、GFAP)和细胞凋亡(TUNEL)。

结果

单侧 DRA 导致持续的双侧神经胶质和炎症反应以及血管退变,而 DRR 则导致短暂的单侧效应。DRA 后的突触前神经退行性变大于 DRR 后的神经退行性变,并在 28 天内进展,与神经胶质增生和巨噬细胞浸润相吻合。

结论

切断术导致脊髓损伤的表现比“真正”撕脱损伤更轻微。我们建议在未来使用 DRA 更可靠地模拟临床撕脱损伤。撕脱伤是一种具有退行性和炎症进展慢性特征的损伤,这从理论上为继发性创伤进展的治疗提供了临床治疗机会的窗口。

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