Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei 10048, Taiwan.
Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei 10048, Taiwan.
Int J Mol Sci. 2021 Mar 28;22(7):3494. doi: 10.3390/ijms22073494.
Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression-edema-ischemia cascade and perineural adhesion that results in excessive shear stress during motion. Despite decades of research, an easily accessible and surgery-free animal model mimicking the mixed etiology is currently lacking, thus limiting our understanding of the disease and the development of effective therapies. In this proof-of-concept study, we used ultrasound-guided perineural injection of a methoxy poly(ethylene glycol)-b-Poly(lactide-co-glycoilide) carboxylic acid (mPEG-PLGA-BOX) hydrogel near the rat's sciatic nerve to induce EN, as confirmed sonographically, electrophysiologically, and histologically. The nerve that was injected with hydrogel appeared unevenly contoured and swollen proximally with slowed nerve conduction velocities across the injected segments, thus showing the compressive features of EN. Histology showed perineural cellular infiltration, deposition of irregular collagen fibers, and a possible early demyelination process, thus indicating the existence of adhesions. The novel method provides a surgery-free and cost-effective way to establish a small-animal model of EN that has mixed compression and adhesion features, thus facilitating the additional elucidation of the pathophysiology of EN and the search for promising treatments.
神经嵌压症（EN）是一种常见且使人虚弱的病症，其发病机制复杂，涉及慢性压迫-水肿-缺血级联反应和神经周围粘连，导致运动时产生过大的剪切力。尽管经过数十年的研究，但目前仍缺乏一种易于获得且无需手术的、可模拟混合病因的动物模型，这限制了我们对该疾病的理解和有效治疗方法的发展。在这项概念验证研究中，我们使用超声引导将甲氧基聚乙二醇-b-聚（乳酸-co-乙醇酸）羧酸（mPEG-PLGA-BOX）水凝胶注射到大鼠坐骨神经附近，以诱导 EN，这在超声、电生理和组织学上均得到了证实。接受水凝胶注射的神经在近端呈现出不均匀的轮廓和肿胀，穿过注射段的神经传导速度减慢，从而显示出 EN 的压迫特征。组织学显示神经周围细胞浸润、不规则胶原纤维沉积和可能的早期脱髓鞘过程，表明存在粘连。这种新方法提供了一种无需手术且具有成本效益的方法来建立具有混合压迫和粘连特征的小型动物 EN 模型，从而有助于进一步阐明 EN 的病理生理学，并寻找有前途的治疗方法。
