Olsen Timothy C, LaGuardia Jonnby S, Chen David R, Lebens Ryan S, Huang Kelly X, Milek David, Noble Mark, Leckenby Jonathan I
Division of Plastic & Reconstructive Surgery, University of Rochester Medical Center, 601 Elmwood Avenue Box 661Rochester, NY 14642, USA.
University of California, 410 Charles E. Young Drive, East Los Angeles, CA 90095, USA.
Regen Med. 2024 Nov;19(11):561-577. doi: 10.1080/17460751.2024.2405318. Epub 2024 Oct 29.
Peripheral nerve injuries lead to severe functional impairments, with rodent models essential for studying regeneration. This review examines key factors affecting outcomes. Age-related declines, like reduced nerve fiber density and impaired axonal transport of vesicles, hinder recovery. Hormonal differences influence regeneration, with BDNF/trkB critical for testosterone and nerve growth factor for estrogen signaling pathways. Species and strain selection impact outcomes, with C57BL/6 mice and Sprague-Dawley rats exhibiting varying regenerative capacities. Injury models - crush for early regeneration, chronic constriction for neuropathic pain, stretch for traumatic elongation and transection for severe lacerations - provide insights into clinically relevant scenarios. Repair techniques, such as nerve grafts and conduits, show that autografts are the gold standard for gaps over 3 cm, with success influenced by graft type and diameter. Time course analysis highlights crucial early degeneration and regeneration phases within the first month, with functional recovery stabilizing by three to six months. Early intervention optimizes regeneration by reducing scar tissue formation, while later interventions focus on remyelination. Understanding these factors is vital for designing robust preclinical studies and translating research into effective clinical treatments for peripheral nerve injuries.
周围神经损伤会导致严重的功能障碍,啮齿动物模型对于研究神经再生至关重要。本综述探讨了影响治疗结果的关键因素。与年龄相关的衰退,如神经纤维密度降低和囊泡轴突运输受损,会阻碍恢复。激素差异影响再生,脑源性神经营养因子/酪氨酸激酶受体B(BDNF/trkB)对睾酮信号通路至关重要,神经生长因子对雌激素信号通路至关重要。物种和品系的选择会影响结果,C57BL/6小鼠和Sprague-Dawley大鼠表现出不同的再生能力。损伤模型——用于早期再生的挤压伤模型、用于神经性疼痛的慢性压迫伤模型、用于创伤性延长的牵拉伤模型和用于严重撕裂伤的横断伤模型——为临床相关情况提供了见解。修复技术,如神经移植和导管,表明自体移植是超过3厘米间隙的金标准,成功率受移植类型和直径影响。时间进程分析突出了第一个月内关键的早期变性和再生阶段,功能恢复在三到六个月时稳定下来。早期干预通过减少瘢痕组织形成来优化再生,而后期干预则侧重于髓鞘再生。了解这些因素对于设计强有力的临床前研究以及将研究转化为周围神经损伤的有效临床治疗至关重要。