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Anatomical, Behavioral and Myological Analysis of the Transgenic Thy1-GFP Rat Following Peripheral Nerve Injury
Stephen W. P. Kemp; Matthew D. Wood; Peter D. Phua; Krisanne N. Stanoulis; Tessa Gordon; Gregory H. Borschel
SickKids Hospital and the University of Toronto, Toronto, ON, Canada
The transgenic Thy-1 GFP rat has recently been proposed as a novel rodent model for evaluating regeneration following peripheral nerve injury. However, it is currently unknown what percentage of their axons fluoresce green, and whether or not they possess different locomotor abilities compared to other strains of laboratory rats. In this experiment, we set out to investigate whether differences in morphology, anatomy, and sensorimotor behaviours exist between transgenic Thy-1 GFP rats when compared to normal type Sprague Dawley rats following unilateral sciatic nerve injury. Animals were randomly assigned to one of four experimental groups: GFP with nerve crush (Group 1); Sprague-Dawley with nerve crush (Group 2); GFP with nerve transection and direct nerve repair (Group 3), and; Sprague-Dawley with nerve transection and direct nerve repair (Group 4). Animals were evaluated serially for a three month period. Evaluation of morphology involved measuring long bone lengths and body weights of each strain. Anatomical parameters were characterized following retrograde labeling of the tibial, common peroneal, and sural nerve. Here, the potential differences between motor and sensory neuronal pools between the two strains were evaluated. Sensorimotor measurements consisted of: (1) ladder rung test; (2) tapered beam with crutch, and; (3) walking track analysis. Endpoint functional analysis consisted of electrophysiological and myological assessments, including compound muscle action potentials (CMAPs), wet muscle weights (gastrocnemius, tibialis anterior, soleus, extensor digitorum longus), and motor unit number estimation (MUNE). Results from the study indicate that subtle morphological, anatomical, and behavioural differences exist between the two strains. The Thy1-GFP rat is a novel transgenic model that enables direct visualization of sciatic nerve regeneration following nerve injury. The utility of this animal model can extend to a variety of clinical lower limb nerve injury paradigms.
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