Gait Disturbances in Dystrophic Hamsters

Abstract

The delta-sarcoglycan-deficient hamster is an excellent model to study muscular dystrophy. Gait disturbances, important clinically, have not been described in this animal model. We applied ventral plane videography (DigiGait) to analyze gait in BIO TO-2 dystrophic and BIO F1B control hamsters walking on a transparent treadmill belt. Stride length was ∼13% shorter (P < .05) in TO-2 hamsters at 9 months of age compared to F1B hamsters. Hindlimb propulsion duration, an indicator of muscle strength, was shorter in 9-month-old TO-2 (247 ± 8 ms) compared to F1B hamsters (272 ± 11 ms; P < .05). Braking duration, reflecting generation of ground reaction forces, was delayed in 9-month-old TO-2 (147 ± 6 ms) compared to F1B hamsters (126 ± 8 ms; P < .05). Hindpaw eversion, evidence of muscle weakness, was greater in 9-month-old TO-2 than in F1B hamsters (17.7 ± 1.2° versus 8.7 ± 1.6°; P < .05). Incline and decline walking aggravated gait disturbances in TO-2 hamsters at 3 months of age. Several gait deficits were apparent in TO-2 hamsters at 1 month of age. Quantitative gait analysis demonstrates that dystrophic TO-2 hamsters recapitulate functional aspects of human muscular dystrophy. Early detection of gait abnormalities in a convenient animal model may accelerate the development of therapies for muscular dystrophy.

Ground reaction forces are more sensitive gait measures than temporal parameters in rodents following rotator cuff injury

“…Previous studies have suggested that braking and propulsion duration may relate to braking and propulsion ground reaction forces (Hampton et al, 2011; Kale et al, 2004). Similarly, Vrinten and colleagues reported a significant correlation between stance time and von Frey thresholds (R=0.67, p<0.001), the latter of which was strongly correlated with an indirect measure of pressure applied during locomotion using light intensity (R=0.63, p<0.001) (Vrinten and Hamers, 2003).…”

“…These results agree with a previous study that did not find significant differences in stance time between rats with or without medial meniscus transection, but did report significant differences in peak vertical and propulsion forces (Allen et al, 2012). Several studies that report changes in temporal parameters following injury only compare to a pre-surgical baseline or uninjured control group, suggesting that these measures are sensitive enough to detect differences above a given functional threshold (Giszter et al, 2008; Hampton et al, 2011; Vrinten and Hamers, 2003). The decreased sensitivity of temporal gait parameters may lead investigators to conclude that there is no effect of a treatment when a difference does indeed exist but cannot be detected (type-II statistical error) (Webb et al, 2011).…”

“…Second, it is noted that non-force couple gait analysis systems can calculate temporal metrics other than stance, propulsion, and braking duration. However, these parameters were selected for the current study as they are commonly reported, easy to interpret, and have been previously associated with the interval available for force generation (Allen et al, 2009; Angeby-Moller et al, 2008; Hampton et al, 2011; Krizsan-Agbas et al, 2014). Despite these limitations, our results clearly demonstrate that ground reaction forces are more sensitive than kinetic parameters to differences in gait in a rat model of rotator cuff injury.…”

“…Importantly, accounting for velocity (which is strongly correlated to stride length and width) as covariate did not improve the sensitivity of these spatial properties when used to analyze rat gait (Allen et al, 2010; Allen et al, 2009; Allen et al, 2011; Shamji et al, 2009). Alternatively, temporal parameters are believed to correspond with force generation, and similar gait patterns have been obtained from both temporal records of paw placement and force plate analysis (Hampton et al, 2011; Kale et al, 2004). Indeed, decreases in temporal parameters (e.g., stance time) may coincide with decreases in kinetic gait parameters (e.g., vertical ground reaction force) observed following injury (Hsu et al, 2011; Sarver et al, 2010; Shih et al, 1993).…”

Detecting ALS and Parkinson’s disease in rats through locomotion analysis

“…A cross-validation method, known as leave-one-out (Efron and Tibshirani 1993), was employed to evaluate the performances of the three models and the sensitivity and specificity values of these three models were found to be better than 90%.…”