Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
J Neurotrauma. 2012 May 20;29(8):1691-703. doi: 10.1089/neu.2011.1857. Epub 2011 Oct 19.
Traumatic neuroma in continuity (NIC) results in profound neurological deficits, and its management poses the most challenging problem to peripheral nerve surgeons today. The absence of a clinically relevant experimental model continues to handicap our ability to investigate ways of better diagnosis and treatment for these disabling injuries. Various injury techniques were tested on Lewis rat sciatic nerves. Optimal experimental injuries that consistently resulted in NIC combined both intense focal compression and traction forces. Nerves were harvested at 0, 5, 13, 21, and 65 days for histological examination. Skilled locomotion and ground reaction force (GRF) analysis were performed up to 9 weeks on the experimental (n=6) and crush-control injuries (n=5). Focal widening, disruption of endoneurium and perineurium with aberrant intra- and extrafascicular axonal regeneration and progressive fibrosis was consistently demonstrated in 14 of 14 nerves with refined experimental injuries. At 8 weeks, experimental animals displayed a significantly greater slip ratio in both skilled locomotor assessments, compared to nerve crush animals (p<0.01). GRFs of the crush- injured animals showed earlier improvement compared to the experimental animals, whose overall GRF patterns failed to recover as well as the crush group. We have demonstrated histological features and poor functional recovery consistent with NIC formation in a rat model. The injury mechanism employed combines traction and compression forces akin to the physical forces at play in clinical nerve injuries. This model may serve as a tool to help diagnose this injury earlier and to develop intervention strategies to improve patient outcomes.
连续性创伤性神经瘤(NIC)会导致严重的神经功能缺损,其治疗是当今周围神经外科医生面临的最具挑战性的问题。缺乏具有临床相关性的实验模型,继续阻碍我们研究这些致残性损伤更好的诊断和治疗方法的能力。已经在Lewis 大鼠坐骨神经上测试了各种损伤技术。最佳的实验性损伤是同时施加强烈的局部压迫和牵引力,可始终导致 NIC。在 0、5、13、21 和 65 天,对神经进行组织学检查。对实验性(n=6)和挤压对照损伤(n=5)进行了长达 9 周的熟练运动和地面反力(GRF)分析。在 14 根经过改良的实验性神经中,始终显示出局部增宽、神经内膜和神经外膜的破坏,以及异常的神经内和神经外轴突再生和进行性纤维化。在熟练运动评估中,与挤压伤动物相比,实验动物在 8 周时的滑动比明显更高(p<0.01)。挤压伤动物的 GRF 较早改善,而实验动物的整体 GRF 模式恢复不佳,与挤压组相似。我们已经在大鼠模型中证明了与 NIC 形成一致的组织学特征和较差的功能恢复。所采用的损伤机制结合了类似于临床神经损伤中存在的物理力的牵拉力和压缩力。该模型可以作为一种工具,帮助更早地诊断这种损伤,并制定干预策略以改善患者的预后。