Pena Maria Teresa, Lahiri Ramanuj, Ebenezer Gigi J, Wheat Stephen W, Figarola John, Truman Richard W, Adams Linda B
United States Department of Health and Human Services, Health Resources and Services Administration, Health Systems Bureau, National Hansen's Disease Program, Baton Rouge, LA, United States.
Department of Neurology, John Hopkins University, Baltimore, MD, United States.
Front Med (Lausanne). 2022 Jun 23;9:879097. doi: 10.3389/fmed.2022.879097. eCollection 2022.
infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for -induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos (), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves. In this study, state-of-the-art technology was used to compare nerve function between uninfected and -infected armadillos. Motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP), which measure changes in the rate of impulse conduction velocity and amplitude, revealed a progression of impairment that was directly correlated with the duration of infection and enabled development of an objective nerve impairment scoring system. Ultrasonography accompanied by color Doppler imaging detected enlargement of the -infected nerves and increased vascularity, possibly due to inflammation. Assessment of epidermal nerve fiber density (ENFD), which shows a length-dependent innervation in armadillos that is similar to humans, identified small fiber degeneration early after infection. Staining for neuromuscular junction (NMJ) integrity, which is an indicator of signal transduction efficiency into skeletal muscle, discerned a markedly lower number and structural integrity of NMJ in -infected armadillo footpads. These tools for assessing nerve injury were used to monitor the effects of intervention therapy. Two potential neuro-protective drugs, ethoxyquin (EQ) and 4-aminopyridine (4-AP), were tested for their ability to ameliorate peripheral nerve injury in -infected armadillos. 4-AP treatment improved MNCV, cMAP, and EFND compared to untreated animals, while EQ had less effect. These results support the armadillo as a model for -induced peripheral nerve injury that can provide insights toward the understanding of NFI progression and contribute to the preclinical investigation of the safety and efficacy of neuro-preventive and neuro-therapeutic interventions for leprosy.
外周神经感染及随后的神经功能损害（NFI），尤其是对反应性发作的反应，是麻风病的特征。由于与麻风病相关的大部分（如果不是全部）残疾和污名都源于NFI的直接或间接影响，因此需要改进针对麻风病所致神经损伤的治疗方法。九带犰狳与人类一样，表现出麻风病的完整临床谱以及外周神经的广泛受累。在本研究中，使用了最先进的技术来比较未感染和感染麻风分枝杆菌的犰狳之间的神经功能。运动神经传导速度（MNCV）和复合肌肉动作电位（cMAP）用于测量冲动传导速度和幅度的变化，揭示了与麻风分枝杆菌感染持续时间直接相关的损害进展，并促成了一个客观的神经损伤评分系统的建立。超声检查结合彩色多普勒成像检测到感染麻风分枝杆菌的神经增粗且血管增多，这可能是由于炎症所致。对表皮神经纤维密度（ENFD）的评估显示，犰狳中存在与人类相似且与长度相关的神经支配，在感染麻风分枝杆菌后早期就发现了小纤维变性。对神经肌肉接头（NMJ）完整性进行染色，这是信号转导至骨骼肌效率的一个指标，发现在感染麻风分枝杆菌的犰狳脚垫中NMJ的数量和结构完整性明显降低。这些评估神经损伤的工具被用于监测干预治疗的效果。测试了两种潜在的神经保护药物乙氧喹（EQ）和4-氨基吡啶（4-AP）改善感染麻风分枝杆菌的犰狳外周神经损伤的能力。与未治疗的动物相比，4-AP治疗改善了MNCV、cMAP和ENFD，而EQ的效果较小。这些结果支持将犰狳作为麻风分枝杆菌所致外周神经损伤的模型，该模型可为理解NFI进展提供见解，并有助于对麻风病神经预防和神经治疗干预措施的安全性和有效性进行临床前研究。
