Center for Orthopaedic Research and Translational Science, The Pennsylvania State University, Hershey, PA, USA.
Penn State College of Medicine, The Pennsylvania State University, Hershey, PA, USA.
Foot Ankle Int. 2023 Dec;44(12):1278-1286. doi: 10.1177/10711007231198822. Epub 2023 Oct 11.
This study aimed to mimic the changes from Charcot neuropathic arthropathy in humans by examining the effects of exposing diet-induced obese (DIO) mice to neurotrauma through a regimented running protocol.
Forty-eight male wild-type C57BL/6J mice were obtained at age 6 weeks and separated into 2 groups for diet assignment. After a 1-week acclimation period, half of the mice consumed a high-fat diet (60% fat by kcal) ad libitum to facilitate neuropathic diet-induced obesity whereas the other half were control mice and consumed an age-matched standard low-fat control diet (10% fat by kcal). At age 12 weeks, half of the animals from each group were subjected to a high-intensity inclined treadmill running protocol, which has been previously demonstrated to induce neurotrauma. Sensory testing and radiographic analyses were periodically performed. Histopathologic analyses were performed post killing.
DIO mice had significantly higher bodyweights, higher body fat percentages, and lower bone mineral density than wildtype control mice that were fed a normal diet throughout the experiment ( < .001 for each). DIO mice displayed significantly reduced sensory function in week 1 ( = .005) and this worsened over time, requiring 20.6% more force for paw withdrawal by week 10 ( < .001). DIO mice that ran demonstrated greater midfoot subluxation and tarsal instability over all time points compared with normal-diet mice that ran ( < .001). Histopathologic analyses revealed that DIO mice that ran demonstrated significant changes compared with controls that ran ( < .001 for each parameter).
Changes akin to the earliest changes observed in or before joint destruction identified in diabetic Charcot neuropathic arthropathy in humans were observed.
There is currently no standard of treatment for patients with Charcot neuropathic arthropathy. This study establishes a protocol for an animal model that can be used to study and compare interventions to treat this disease.
本研究旨在通过对饮食诱导肥胖（DIO）小鼠进行有规律的跑步方案的神经创伤来模拟人类夏科氏神经病理性关节病的变化。
48 只雄性野生型 C57BL/6J 小鼠在 6 周龄时获得，并分为 2 组进行饮食分配。经过 1 周的适应期，一半的小鼠随意摄入高脂肪饮食（按热量计 60%脂肪）以促进神经病变性饮食诱导肥胖，而另一半则为对照小鼠并摄入年龄匹配的标准低脂对照饮食（按热量计 10%脂肪）。在 12 周龄时，每组一半的动物接受高强度倾斜跑步机跑步方案，该方案以前已被证明可引起神经创伤。定期进行感觉测试和放射学分析。处死前进行组织病理学分析。
与整个实验过程中都摄入正常饮食的野生型对照小鼠相比，DIO 小鼠的体重明显更高，体脂肪百分比更高，骨矿物质密度更低（均<0.001）。DIO 小鼠在第 1 周时的感觉功能明显下降（=0.005），随着时间的推移，这种情况恶化，第 10 周时，前脚撤回所需的力增加了 20.6%（<0.001）。与正常饮食跑步的 DIO 小鼠相比，所有时间点 DIO 跑步小鼠的中足半脱位和跗骨不稳定程度都更大（均<0.001）。组织病理学分析显示，与跑步对照相比，跑步的 DIO 小鼠表现出明显的变化（每个参数均<0.001）。
观察到类似于人类糖尿病性夏科氏神经病理性关节病中观察到的关节破坏之前或早期变化。
目前尚无针对夏科氏神经病理性关节病患者的标准治疗方法。本研究建立了一种动物模型的方案，可以用于研究和比较治疗这种疾病的干预措施。
