Noble Mark, Tseng Kuang-Ching Chris, Li Haiyan, Elfar John C
University of Rochester, Stem Cell Regenerative Medicine Institute, Department of Molecular Genetics, 601 Elmwood Ave, Rochester, NY.
Department of Orthopaedics, University of Rochester, 601 Elmwood Ave, Rochester, NY.
Mil Med. 2019 Mar 1;184(Suppl 1):379-385. doi: 10.1093/milmed/usy399.
Traumatic peripheral nerve injury (TPI) is a major medical problem without effective treatment options. There is no way to diagnose or treat an incomplete injury and delays contribute to morbidity. We examined 4-aminopyridine (4-AP), a potassium-channel blocker as a possible treatment for TPI.
We used standard mouse models of TPI with functional outcomes including sciatic-functional-index, sensory indices, and electrodiagnostics; in addition to standard immunohistochemical, and electron microscopic correlates of axon and myelin morphology.
Sustained early 4-AP administration increased the speed and extent of behavioral recovery too rapidly to be explained by axonal regeneration. 4-AP also enhanced recovery of nerve conduction velocity, promoted remyelination, and increased axonal area post-injury. 4-AP treatment also enabled the rapid distinction between incomplete and complete nerve lesions.
4-AP singularly provides both a new potential therapy to promote durable recovery and remyelination in acute peripheral nerve injury and a means of identifying lesions in which this therapy would be most likely to be of value. The ability to distinguish injuries that may respond to extended therapy without intervention can offer benefit to wounded soldiers.
创伤性周围神经损伤（TPI）是一个主要的医学问题，目前尚无有效的治疗方案。对于不完全损伤，尚无诊断或治疗方法，而延误治疗会导致病情加重。我们研究了钾通道阻滞剂4-氨基吡啶（4-AP）作为TPI的一种可能治疗方法。
我们使用TPI的标准小鼠模型，评估其功能结果，包括坐骨神经功能指数、感觉指数和电诊断；此外，还进行了标准的免疫组织化学以及轴突和髓鞘形态的电子显微镜相关检查。
早期持续给予4-AP可加快行为恢复的速度和程度，其速度之快无法用轴突再生来解释。4-AP还可提高神经传导速度的恢复，促进髓鞘再生，并增加损伤后轴突面积。4-AP治疗还能快速区分不完全和完全性神经损伤。
4-AP单独使用既为急性周围神经损伤促进持久恢复和髓鞘再生提供了一种新的潜在治疗方法，也为确定最有可能从该治疗中获益的损伤提供了一种手段。在不进行干预的情况下区分可能对延长治疗有反应的损伤的能力，可能会使受伤士兵受益。
