Animal model detects early pathologic changes of Charcot neuropathic arthropathy

Stauch, Chris; Fanburg‐Smith, Julie C.; Walley, Kempland C.; King, Jesse; Murie, Benjamin; Kim, Morgan; Koroneos, Zachary; Waning, David L.; Elfar, John C.; Aynardi, Michael

doi:10.1016/j.anndiagpath.2021.151878

Cited by 1 publication

(4 citation statements)

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“…This model builds on a previous pilot model by Stauch et al 34 that investigated a viable animal model for idiopathic neuroarthropathy. The present study builds on the previous model by including the appropriate controls to establish the combined effect of obesity and microtrauma in the described mouse model for CNA.…”

Section: Discussionmentioning

confidence: 99%

“…and included observations of mid-paw pathology of the bone and soft tissues similar to previous work. 34 The following measures were scored: (1) perichondral ossification of the articular surface; (2) endochondral ossification of the subchondral location, interpreted as perichondral endochondral ossification causing osteosclerosis (the earliest changes observed in human CNA); (3) distance of the articular surface to the closest marrow space measured in microscopic arrow lengths; and (4) cortical endochondral ossification. Scoring ranges included the following: 0 = healthy/normal, 1 = minor changes within normal range or below level of detection, 2 = pathologic (moderate) changes, 3 = pathologic (severe) changes.…”

Section: Methodsmentioning

confidence: 99%

“…However, a recently published pilot study by Stauch et al exposed a murine, neuropathic model with microtrauma and produced Charcot-like neuroarthropathic changes mimicking humans. 3,4,10,12,20,22,26,32,34 The purpose of this study was to further investigate a mouse model for CNA through a neurotraumatic mechanism. This is the first multivariable designed study used to evaluate an animal model for CNA and expands on previous work in terms of cohort size and controls.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Establishment of a Neurodegenerative Charcot Mouse Model

Koroneos,

Ptasinski,

Stauch

et al. 2023

Foot Ankle Int.

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Background: 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. Methods: 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. Results: 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 ( P < .001 for each). DIO mice displayed significantly reduced sensory function in week 1 ( P = .005) and this worsened over time, requiring 20.6% more force for paw withdrawal by week 10 ( P < .001). DIO mice that ran demonstrated greater midfoot subluxation and tarsal instability over all time points compared with normal-diet mice that ran ( P < .001). Histopathologic analyses revealed that DIO mice that ran demonstrated significant changes compared with controls that ran ( P < .001 for each parameter). Conclusion: Changes akin to the earliest changes observed in or before joint destruction identified in diabetic Charcot neuropathic arthropathy in humans were observed. Clinical Relevance: 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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%