Department of Orthopaedics and Rehabilitation, Center for Orthopaedic Research and Translational Science, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Department of Orthopedic Surgery, Hanyang University College of Medicine, Hayang University Guri Hospital, Guri-si, Gyeonggi-do, 11923, South Korea.
Mil Med. 2021 Jan 25;186(Suppl 1):696-703. doi: 10.1093/milmed/usaa344.
Functional recovery following primary nerve repair of a transected nerve is often poor even with advanced microsurgical techniques. Recently, we developed a novel sciatic nerve transection method where end-to-end apposition of the nerve endings with minimal gap was performed with fibrin glue. We demonstrated that transected nerve repair with gluing results in optimal functional recovery with improved axonal neurofilament distribution profile compared to the end-to-end micro-suture repair. However, the impact of axonal misdirection and misalignment of nerve fascicles remains largely unknown in nerve-injury recovery. We addressed this issue using a novel nerve repair model with gluing.
In our complete "Flip and Transection with Glue" model, the nerve was "first" transected to 40% of its width from each side and distal stump was transversely flipped, then 20 µL of fibrin glue was applied around the transection site and the central 20% nerve was completely transected before fibrin glue clotting. Mice were followed for 28 days with weekly assessment of sciatic function. Immunohistochemistry analysis of both sciatic nerves was performed for neurofilament distribution and angiogenesis. Tibialis anterior muscles were analyzed for atrophy and histomorphometry.
Functional recovery following misaligned repair remained persistently low throughout the postsurgical period. Immunohistochemistry of nerve sections revealed significantly increased aberrant axonal neurofilaments in injured and distal nerve segments compared to proximal segments. Increased aberrant neurofilament profiles in the injured and distal nerve segments were associated with significantly increased nerve blood-vessel density and branching index than in the proximal segment. Injured limbs had significant muscle atrophy, and muscle fiber distribution showed significantly increased numbers of smaller muscle fibers and decreased numbers of larger muscle fibers.
These findings in a novel nerve transection mouse model with misaligned repair suggest that aberrant neurofilament distributions and axonal misdirections play an important role in functional recovery and muscle atrophy.
即使采用先进的显微外科技术，原发性神经修复后神经的功能恢复通常也很差。最近，我们开发了一种新的坐骨神经横断方法，该方法使用纤维蛋白胶使神经末梢端对端吻合，间隙最小。我们证明，与端对端微缝合修复相比，用胶粘合修复断端神经可导致最佳的功能恢复，并改善轴突神经丝分布谱。然而，在神经损伤恢复中，轴突的错位和神经束的不对准的影响在很大程度上仍然未知。我们使用新型的粘合神经修复模型解决了这个问题。
在我们的完全“翻转和粘合”模型中，神经首先从每一侧横断 40%的宽度，然后将远端残端横向翻转，然后在横断部位周围涂抹 20µL 纤维蛋白胶，在纤维蛋白胶凝固之前完全横断中央 20%的神经。用每周评估坐骨神经功能的方法对小鼠进行 28 天的随访。对坐骨神经进行神经丝分布和血管生成的免疫组织化学分析。分析比目鱼肌萎缩和组织形态计量学。
在整个术后期间，错位修复后的功能恢复仍然持续较低。神经切片的免疫组织化学显示，与近端节段相比，损伤和远端神经节段的异常轴突神经丝明显增加。损伤和远端神经节段中异常神经丝谱的增加与近端节段相比，神经血管密度和分支指数显著增加。受伤的肢体出现明显的肌肉萎缩，肌肉纤维分布显示较小的肌肉纤维数量明显增加，较大的肌肉纤维数量减少。
在新型的神经横断小鼠模型中，错位修复后的这些发现表明，异常的神经丝分布和轴突错位在功能恢复和肌肉萎缩中起着重要作用。
