Yeoh Stewart, Warner Wesley S, Eli Ilyas, Mahan Mark A
J Neurosurg. 2020 Nov 6;135(3):893-903. doi: 10.3171/2020.5.JNS193448. Print 2021 Sep 1.
Traditional animal models of nerve injury use controlled crush or transection injuries to investigate nerve regeneration; however, a more common and challenging clinical problem involves closed traction nerve injuries. The authors have produced a precise traction injury model and sought to examine how the pathophysiology of stretch injuries compares with that of crush and transection injuries.
Ninety-five late-adolescent (8-week-old) male mice underwent 1 of 7 injury grades or a sham injury (n > 10 per group): elastic stretch, inelastic stretch, stretch rupture, crush, primary coaptation, secondary coaptation, and critical gap. Animals underwent serial neurological assessment with sciatic function index, tapered beam, and von Frey monofilament testing for 48 days after injury, followed by trichrome and immunofluorescent nerve histology and muscle weight evaluation.
The in-continuity injuries, crush and elastic stretch, demonstrated different recovery profiles, with more severe functional deficits after crush injury than after elastic stretch immediately following injury (p < 0.05). However, animals with either injury type returned to baseline performance in all neurological assessments, accompanied by minimal change in nerve histology. Inelastic stretch, a partial discontinuity injury, produced more severe neurological deficits, incomplete return of function, 47% ± 9.1% (mean ± SD) reduction of axon counts (p < 0.001), and partial neuroma formation within the nerve. Discontinuity injuries, including immediate and delayed nerve repair, stretch rupture, and critical gap, manifested severe, long-term neurological deficits and profound axonal loss, coupled with intraneural scar formation. Although repaired nerves demonstrated axon regeneration across the gap, rupture and critical gap injuries demonstrated negligible axon crossing, despite rupture injuries having healed into continuity.
Stretch-injured nerves present unique pathology and functional deficits compared with traditional nerve injury models. Because of the profound neuroma formation, stretch injuries represent an opportunity to study the pathophysiology associated with clinical injury mechanisms. Further validation for comparison with human injuries will require evaluation in a large-animal model.
传统的神经损伤动物模型采用可控的挤压或横断损伤来研究神经再生；然而，一个更常见且具有挑战性的临床问题涉及闭合性牵拉伤性神经损伤。作者建立了一种精确的牵拉伤模型，并试图研究牵拉伤的病理生理学与挤压伤和横断伤相比有何不同。
95只青春期晚期（8周龄）雄性小鼠接受7种损伤等级中的1种或假损伤（每组n>10）：弹性拉伸、非弹性拉伸、拉伸断裂、挤压、一期吻合、二期吻合和临界间隙。在损伤后48天，对动物进行坐骨神经功能指数、锥形束和von Frey单丝测试的系列神经学评估，随后进行三色和免疫荧光神经组织学检查以及肌肉重量评估。
连续性损伤，即挤压伤和弹性拉伸伤，表现出不同的恢复情况，损伤后立即出现的挤压伤比弹性拉伸伤的功能缺陷更严重（p<0.05）。然而，两种损伤类型的动物在所有神经学评估中均恢复到基线表现，同时神经组织学变化最小。非弹性拉伸，一种部分连续性损伤，产生更严重的神经功能缺陷、功能不完全恢复、轴突数量减少47%±9.1%（平均值±标准差）（p<0.001）以及神经内部分神经瘤形成。连续性中断损伤，包括即时和延迟神经修复、拉伸断裂和临界间隙，表现出严重的长期神经功能缺陷和严重的轴突损失，同时伴有神经内瘢痕形成。尽管修复后的神经显示轴突在间隙处再生，但断裂和临界间隙损伤的轴突穿越可忽略不计，尽管断裂伤已愈合为连续性。
与传统神经损伤模型相比，牵拉伤性神经呈现出独特的病理学和功能缺陷。由于严重的神经瘤形成，牵拉伤为研究与临床损伤机制相关的病理生理学提供了机会。与人类损伤进行比较的进一步验证将需要在大型动物模型中进行评估。
