Establishment of a Neurodegenerative Mouse Model for Charcot Neuropathic Arthropathy
| Autor: | Zachary Koroneos, Anna Ptasinski, Chris M. Stauch BS, Laura R. Luick MD, Julie C. Fanburg-Smith, Michael C. Aynardi MD |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Foot & Ankle Orthopaedics, Vol 7 (2022) |
| Druh dokumentu: | article |
| ISSN: | 2473-0114 24730114 |
| DOI: | 10.1177/2473011421S00287 |
| Popis: | Category: Basic Sciences/Biologics; Diabetes Introduction/Purpose: Neuropathic arthropathy (Charcot) is a progressive and debilitating joint destruction and has neurovascular and neurotraumatic etiologies which are commonly observed in type II Diabetes. This stems from the loss of protective sensation through peripheral neuropathy, cartilage loss, and fragmentation. To model this condition, diabetic obese mice have demonstrated insulin resistance and peripheral neuropathy similar to that seen in type II diabetes in humans. We hypothesized that exposing these diabetic induced, neuropathic (DIN) mice to neuro-trauma through a regimented running protocol would produce a Charcot like, neurodegenerative state seen in human diabetic Charcot when compared to controls. Methods: Following IAUCUC approval, 24 DIN wild-type C57BL/6J, and 24 wildtype control (WTC) C57BL/6J mice were obtained (Jackson Labs, Bar Harbor, ME) at 6-weeks-old. After a one-week acclimation period, DIN mice consumed a high-fat diet (60% fat by kcal) ad libitum to facilitate neuropathic diet-induced obesity while WTC mice consumed an age-matched standard low-fat control diet (10% fat by kcal). At 12-weeks-old, half of the animals from each group were subjected to a high-intensity inclined treadmill running protocol (+R), which has been previously shown to induce neurotrauma. The protocol involved 25 minutes of running 4 times per week for 10 weeks for both groups. Von Frey filament sensory testing, and radiographic analyses were performed at weeks 0,5 and 10. After 10 weeks, animals were sacrificed; histopathologic analyses were performed to evaluate the navicular-cuneiform joint articular cartilage, sub-chondral and cortical bone, distance to marrow space, and soft tissue including nerves, and vessels. Results: DIN+R mice displayed significantly reduced sensory function in Von Frey filament testing in week 1 (P |
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