Females and males exhibit similar functional, mechanical, and morphological outcomes in a rat model of posttraumatic elbow contracture

Abstract

Posttraumatic joint contracture (PTJC) is a debilitating condition characterized by loss of joint motion following injury. Previous work in a rat model of elbow PTJC investigated disease etiology, progression, and recovery in only male animals; this study explored sex-based differences. Rat elbows were subjected to a unilateral anterior capsulotomy and lateral collateral ligament transection followed by 42 days of immobilization and 42 days of free mobilization. Grip strength and gait were collected throughout the free mobilization period while joint mechanical testing, microcomputed tomography and histological analysis were performed postmortem. Overall, few differences were seen between sexes in functional, mechanical, and morphological outcomes with PTJC being similarly debilitating in male and female animals. Functional measures of grip strength and gait showed that, while some baseline differences existed between sexes, traumatic injury produced similar deficits that remained significantly different long-term when compared to control animals. Similarly, male and female animals both had significant reductions in joint range of motion due to injury. Ectopic calcification (EC), which had not been previously evaluated in this injury model, was present in all limbs on the lateral side. Injury caused increased EC volume but did not alter mineral density regardless of sex.Furthermore, histological analysis of the anterior capsule showed minor differences between sexes for inflammation and thickness but not for other histological parameters. A quantitative understanding of sex-based differences associated with this injury model will help inform future therapeutics aimed at reducing or preventing elbow PTJC.

Investigating the Effects of Physical Therapy Timing, Intensity and Duration on Post-Traumatic Joint Contracture in a Rat Elbow Model

“…While this provides useful data to build upon, other key outcomes including in vivo joint function or tissue microanatomy would provide a more comprehensive assessment of the effects of the various experimental physical therapy strategies. Nevertheless, previous work demonstrated that poor post-mortem joint motion data was associated with functional deficits of grip strength and gait, as well as pathological joint capsule tissue via histology, which would be expected in the various experimental groups where therapy was not effective (17)(18)(19)(20)26). Lastly, it is possible that treadmill walking was not the optimal forelimb physical therapy in rats.…”

Pleiotropic Effects of Simvastatin and Losartan in Preclinical Models of Post-Traumatic Elbow Contracture

“…Future work could increase sample sizes, modify the dosing strategies, and evaluate other drug toxicity parameters [e.g., pain, liver dysfunction, and muscle damage ( MacDonald and Halleck, 2004 ; Schachter, 2005 ; Sica et al, 2005 )], functional deficiencies [e.g., gait and grip strength ( Reiter et al, 2019 )], elbow motions [i.e., pronation and supination ( Dunham et al, 2017a )], and time points post-trauma. Further, although only male rats were included in this study and previous work showed minor sex-dependent progression of PTJC ( Reiter et al, 2021b ), the effect of drug treatment in female rats could be different and should be considered. Since drugs were given systemically, knowledge about the pharmacokinetics and bioavailability of drugs within the elbow’s synovial space would be critical for understanding the drug mechanisms of action and optimizing and choosing alternative dosing and delivery strategies (e.g., use of nanoparticles, intra-articular injections, drinking water, or topical application).…”

“…In this IACUC-approved study, male Long-Evans rats ( n = 35; 330–370 g; Charles River Laboratories International, Wilmington, MA) were subjected to an established elbow injury model ( Lake et al, 2016 ; Dunham et al, 2017b ); male rats were selected because this PTJC model was developed using males and few sex-based differences have been observed ( Reiter et al, 2021b ). Briefly, unilateral elbows were subjected to anterior capsulotomy and transection of the lateral collateral ligament followed by a period of immobilization (0–42 days post-injury via bandage/wraps) and then free mobilization (i.e., unrestricted cage activity; 42–84 days post-injury) ( Figure 1A ).…”

“…Therefore, this study aimed to evaluate the effects of SV and LS in two established preclinical models of contracture. Two SV and LS dosing strategies were tested in an elbow-specific rat injury model in vivo , which normally causes loss of elbow function, capsule fibrosis, and mild arthritis ( Lake et al, 2016 ; Dunham et al, 2017a ; Dunham et al, 2017b ; Dunham et al, 2018a ; Dunham et al, 2018b ; Dunham et al, 2019 ; Dunham et al, 2020 ; Dunham et al, 2021 ; Reiter et al, 2019 ; Reiter et al, 2021a ; Reiter et al, 2021b ) . The in vivo model provides translatability of SV and LS therapy and joint-wide impact on multiple soft tissues (i.e., capsule and cartilage).…”

Computer Intelligent Algorithm in the Recovery of the Elbow Joint Sports Injury Model

“…The three pneumatic muscles are connected to the forearm disc and the upper arm disc through the Hooke hinge, and there is an axial rotation between the Hooke hinges. The upper end of the support rod is connected with the centre point of the forearm disc through the Hooke hinge, and there is an axial rotation between the Hooke hinges [ 6 ]. The lower end is fixedly connected with the centre point of the upper arm disc through a thread.…”