Acute Ankle Sprain in a Mouse Model

Hubbard-Turner, Tricia; Wikstrom, Erik A.; Guderian, Sophie; Turner, Michael J.

doi:10.1249/mss.0b013e3182897d25

Cited by 28 publications

(93 citation statements)

References 15 publications

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“…This lesser activity level was primarily responsible for the increased LV EDD, LVPW, h/r, reduced passive filling velocity, and E/A ratio by 6 to 9 months of age. Previously our laboratory observed markedly reduced activity levels in the ATFL/CFL mice compared to the SHAM and CFL mice throughout the first 4 weeks following a surgically induced ankle sprain (Hubbard-Turner et al 2013). Our current findings highlight the secondary impact of a musculoskeletal injury on reduced physical activity levels and the acceleration in negative alterations of LV structure and performance, where the increased LV h/r and decline in E/A ratio was accelerated for the ATFL/CFL mice compared to the SHAM group.…”

Section: Discussionmentioning

confidence: 85%

“…All surgical procedures have been described previously (Hubbard-Turner et al 2013). Briefly, at 7 weeks of age, each mouse was anesthetized using isoflurane gas at 4.0 % concentration in oxygen with a 800 cm 3 /min flow rate.…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…A lower body musculoskeletal injury, such as an ankle sprain, has been found to negatively influence physical activity early in life (Hubbard-Turner et al 2013;Verhagen et al 1995). Additionally, ankle sprains are the most common musculoskeletal injury suffered during physical activity and sport (Fernandez et al 2007;Hootman et al 2007) and the CDC has reported that lower extremity injury is a leading reason why people stop participating in lifelong physical activity (Centers for Disease Control and Prevention 2009).…”

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confidence: 99%

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Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Turner

Guderian

Wikstrom

et al. 2016

AGE

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We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p < 0.0001). Beginning at 6 months of age, interaction (group × age) was noted with LV posterior wall thickness-to-radius ratios (h/r) where h/r increased with age in the ATFL/CFL and SHAMSED mice while the SHAM and CFL mice exhibited decreased h/r with age (p = 0.0002). Passive filling velocity (E wave) was significantly greater in the SHAM mice and lowest for the ATFL/CFL and SHAMSED mice (p < 0.0001) beginning at 9 months of age. Active filling velocity (A wave) was not different between groups (p = 0.10). Passive-to-active filling velocity ratio (E/A ratio) was different between groups (p < 0.0001), with higher ratios for the SHAM mice and lower ratios for the ATFL/CFL and SHAMSED mice in response to physical activity beginning at 9 months of age. Passive-toactive filling velocity ratio decreased with age (p < 0.0001). Regular physical activity throughout the lifespan improved LV structure, passive filling velocity, and E/A ratio by 6 to 9 months of age and attenuated any negative alterations throughout the second half of life. The diastolic filling differences were found to be significantly related to the amount of activity performed by 9 months and at the end of the lifespan.

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Section: Discussionmentioning

confidence: 85%

Section: Surgical Proceduresmentioning

confidence: 99%

mentioning

confidence: 99%

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Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Turner

Guderian

Wikstrom

et al. 2016

AGE

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“…25 Each mouse was anesthetized with 4% isoflurane gas and supplemental oxygen. The right ankle was then shaved and cleaned with alcohol, followed by a chlorhexidine scrub.…”

Section: Surgery Proceduresmentioning

confidence: 99%

“…After the site was prepared, the mouse remained anesthetized and was moved to a sterile surgical field under a microscope. 25 To help guide our transections, we used the techniques of Kim et al 26 For the CFL-only group, a small incision was made under the microscope using sterile equipment. The skin was retracted, the CFL was transected, and the skin was closed using 2 drops of formulated cyanoacrylate surgical adhesive.…”

Section: Surgery Proceduresmentioning

confidence: 99%

Acute Ankle Sprain in a Mouse Model: Changes in Knee-Joint Space

Hubbard-Turner

Wikstrom

Guderian

et al. 2017

Journal of Athletic Training

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Context: Ankle sprains remain the most common orthopaedic injury. Conducting long-term studies in humans is difficult and costly, so the long-term consequences of an ankle sprain are not entirely known. Objective: To measure knee-joint space after a single surgically induced ankle sprain in mice. Design: Randomized controlled trial. Setting: University research laboratory. Patients or Other Participants: Thirty male mice (CBA/2J) were randomly placed into 1 of 3 surgical groups: the transected calcaneofibular ligament (CFL) group, the transected anterior talofibular ligament/CFL group, or a sham treatment group. The right ankle was operated on in all mice. Main Outcome Measure(s): Three days after surgery, all of the mice were individually housed in cages containing a solid-surface running wheel, and daily running-wheel measurements were recorded. Before surgery and every 6 weeks after surgery, a diagnostic ultrasound was used to measure medial and lateral knee-joint space in both hind limbs. Results: Right medial (P = .003), right lateral (P = .002), left medial (P = .03), and left lateral (P = .002) knee-joint spaces decreased across the life span. The mice in the anterior talofibular ligament/CFL group had decreased right medial (P = .004) joint space compared with the sham and CFL groups starting at 24 weeks of age and continuing throughout the life span. No differences occurred in contralateral knee-joint degeneration among any of the groups. Conclusions: Based on current data, mice that sustained a surgically induced severe ankle sprain developed greater joint degeneration in the ipsilateral knee. Knee degeneration could result from accommodation to the laxity of the ankle or biomechanical alterations secondary to ankle instability. A single surgically induced ankle sprain could significantly affect knee-joint function.

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Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

Blaker

Clarke

Little

2016

Journal Orthopaedic Research

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Post-traumatic osteoarthritis (PTOA) is defined by its development after joint injury. Factors contributing to the risk of PTOA occurring, the rate of progression, and degree of associated disability in any individual, remain incompletely understood. What constitutes an "OA-inducing injury" is not defined. In line with advances in the traumatic brain injury field, we propose the scope of PTOA-inducing injuries be expanded to include not only those causing immediate structural damage and instability (Type I), but also those without initial instability/damage from moderate (Type II) or minor (Type III) loading severity. A review of the literature revealed this full spectrum of potential PTOA subtypes can be modeled in mice, with 27 Type I, 6 Type II, and 4 Type III models identified. Despite limitations due to cartilage anatomy, joint size, and bio-fluid availability, mice offer advantages as preclinical models to study PTOA, particularly genetically modified strains. Histopathology was the most common disease outcome, cartilage more frequently studied than bone or synovium, and meniscus and ligaments rarely evaluated. Other methods used to examine PTOA included gene expression, protein analysis, and imaging. Despite the major issues reported by patients being pain and biomechanical dysfunction, these were the least commonly measured outcomes in mouse models. Informative correlations of simultaneously measured disease outcomes in individual animals, was rarely done in any mouse PTOA model. This review has identified knowledge gaps that need to be addressed to increase understanding and improve prevention and management of PTOA. Preclinical mouse models play a critical role in these endeavors. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:424-439, 2017.

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Acute Ankle Sprain in a Mouse Model

Abstract: The results of this study indicate that a mouse model can be used to induce mechanical instability in the ankle.

Cited by 28 publications

References 15 publications

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Acute Ankle Sprain in a Mouse Model: Changes in Knee-Joint Space

Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

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