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

Abstract

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.

Prolonged Rest, Long-Term Dynamic Balance, and Gait in a Mouse Ankle-Sprain Model

“…As a result, future authors using animal models should focus on more precise measures of muscle mechanics, nervous system function, and biochemical markers to elucidate the underlying mechanisms as to why prolonged rest appears protective against centrally mediated changes. Further research is also needed to determine if prolonged rest after severe LAS mitigates lifelong physical activity reductions, ankle posttraumatic osteoarthritis, and other consequences to body systems observed using this mouse LAS model 17,19,21 as well as to explore the contextual dependence among these consequences and measures of sensorimotor function. Additionally, investigators should determine the postinjury time points that represent key points within the cascade of events that therapeutic interventions may be able to mitigate.…”

“…The vivarium had 12hour light-dark cycles with room temperature and relative humidity standardized to 188C to 228C and 20% to 40%, respectively. [16][17][18][19][20][21][22] Water and standard chow (Teklad 8604 Rodent Diet; Harlan, Madison, WI) were provided ad libitum. [16][17][18][19][20][21][22] The Institutional Animal Care and Use Committee at the University of North Carolina at Charlotte approved all study procedures as meeting the US Department of Agriculture and Animal Welfare Act guidelines for the appropriate treatment of animal subjects.…”

“…Surgical procedures replicated those previously described for mice with severe LASs. [16][17][18][19][20][21] In brief, mice were anesthetized before having the right ankle prepared for surgery. Once anesthetized, mice were moved to a sterile surgical field under a warming lamp, where a small curvilinear incision was made behind the lateral malleolus using sterile equipment and a microscope.…”

“…Mild and severe LAS mouse models have been developed. These models mimic the short-term 16 and residual [17][18][19][20][21] symptoms of mild and severe human LAS, respectively. More specifically, these models have demonstrated both acute and chronic sensorimotor dysfunction as evidenced by impaired dynamic balance and altered gait outcomes.…”

“…More specifically, these models have demonstrated both acute and chronic sensorimotor dysfunction as evidenced by impaired dynamic balance and altered gait outcomes. 16,18,20 As a result, these models [16][17][18][19][20][21] may provide an opportunity to gather preclinical data regarding the effectiveness of LAS interventions, including the effectiveness of prolonged rest or immobilization (or both) on dynamic balance and gait outcomes after a severe LAS. However, the validity of these models in providing insights into the efficacy and effectiveness of therapeutic interventions has not yet been investigated.…”