Department of Neurosurgery, School of Medicine and Health Sciences, Faculty VI, University of Oldenburg, Carl von Ossietzky Str. 9-11, 26129, Oldenburg, Germany.
Department of Neuroscience, School of Medicine and Health Sciences, Faculty VI, University of Oldenburg, 26129, Oldenburg, Germany.
Acta Neurochir (Wien). 2018 Jun;160(6):1269-1281. doi: 10.1007/s00701-018-3544-6. Epub 2018 Apr 14.
Neuromas are pathologic nerve distensions caused by a nerve's response to trauma, resulting in a dysfunctional to non-functional nerve. Depending on the severance of the affected nerve, the resulting neuroma can be differentiated into continuous and stump neuroma. While neuroma formation has been investigated in animal models with enormous regenerative capacity, the search for differences in human response to nerve trauma on a molecular level ultimately seeks to identify reasons for functionally successful versus unsuccessful regeneration after peripheral nerve trauma in man.
In the present study, the regenerative potential of axons and the capability of Schwann cells (SC) to remyelinate regenerating axons was quantitatively and segmentally analyzed and compared within human neuroma in-continuity and discontinuity.
For the stump neuroma and the neuroma in-continuity, there was a significant reduction of the total number of axons (86% stump neuroma and 91% neuroma in-continuity) from the proximal to the distal part of the neuroma, while the amount of fibrotic tissue increased, respectively. Labeling the myelin sheath of regenerating axons revealed a remyelination of regenerating axons by SCs in both neuroma types. The segmented analysis showed no distinct alterations in the number and spatial distribution of regenerating, mature, and myelinated axons between continuous and discontinuous neuroma.
The quantitative and segmented analysis showed no distinct alterations in the number and spatial distribution of regenerating, mature, and myelinated axons between continuous and discontinuous neuroma, while the extensive expression of Gap43 in up to 55% of the human neuroma axons underlines their regenerative capacity independent of whether the neuroma is in continuity or discontinuity. Remyelination of Gap43-positive axons suggests that the capability of SCs to remyelinate regenerating axons is preserved in neuroma tissue.
神经瘤是由神经对创伤的反应引起的病理性神经扩张，导致神经功能失调或无功能。根据受影响神经的切断情况，由此产生的神经瘤可以分为连续性和残端性神经瘤。虽然在具有巨大再生能力的动物模型中已经研究了神经瘤的形成，但从分子水平上寻找人类对神经创伤反应的差异，最终目的是确定人类周围神经创伤后功能成功与不成功再生的原因。
在本研究中，定量和分段分析比较了连续性和不连续性人神经瘤中轴突的再生潜力和施万细胞（SCs）对再生轴突进行髓鞘形成的能力。
对于残端性神经瘤和连续性神经瘤，从近端到神经瘤的远端，轴突的总数（残端性神经瘤为 86%，连续性神经瘤为 91%）显著减少，而纤维化组织的量分别增加。标记再生轴突的髓鞘显示 SC 对两种神经瘤类型中再生轴突进行了髓鞘形成。分段分析显示，连续性和不连续性神经瘤之间再生、成熟和髓鞘化轴突的数量和空间分布没有明显改变。
定量和分段分析显示，连续性和不连续性神经瘤之间再生、成熟和髓鞘化轴突的数量和空间分布没有明显改变，而高达 55%的人神经瘤轴突中 Gap43 的广泛表达强调了它们的再生能力，与神经瘤是否连续性无关。Gap43 阳性轴突的髓鞘形成表明，SCs 对再生轴突进行髓鞘形成的能力在神经瘤组织中得到保留。
