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Neuronal Death and Persistence of Functional Deficits Beyond Postnatal Day 5 (P5) Following Neonatal Nerve Injury in the Rat
Stephen W. P. Kemp, Cameron D. Chiang, Matthew D. Wood, Edward H. Liu, Michael P. Willand, Tessa Gordon and Gregory H. Borschel
Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, ON, Canada
In contrast to adult rat nerve injury models, neonatal nerve crush leads to both massive motor and sensory neuron (DRG) cell death. Death of these neurons results from both the loss of functional contact between the nerve terminals and their targets, and the inability of immature Schwann cells in the distal stump of the injured nerve to sustain regeneration. However, previous research has shown limited to no neuronal death following a nerve crush injury at postnatal day 5 (P5). Following unilateral crush to the right sciatic nerve in both uninjured and postnatal day 3-30 (P3-P30) rats, we sought to: (1) examine both motor and sensory neuron cell death at 1 month proximal to the original injury, a measure of neuronal survival; (2) examine the number of regenerated motor and sensory neurons distal to the original injury, a measure of axonal regeneration and sprouting, and; (3) examine the functional recovery of behavior and muscle parameters following nerve injury. Following the initial surgery, animals were returned to their home cages and their body weights were monitored for a one month period. At 1 month, anatomical parameters of both the spinal cord and dorsal root ganglion (DRG) cells were characterized following retrograde labeling of the sciatic nerve with FluorGold (FG). A 5 mm section distal to the original nerve crush was also harvested for histomorphometry. Following nerve injury at P3, the number of retrogradely labeled motorneurons was reduced to approximately 35%. Animals in both the P5 and P7 nerve crush group also displayed statistically lower motor neuron numbers than uninjured control animals. All nerve injured animal groups (P3-P30) displayed significantly lower DRG counts than controls. In the functional recovery experiments, only animals who underwent nerve crush at P30 recovered normal walking track SFI values at one month following injury. Similar results were seen for extensor digitorum longus (EDL) muscle twitch/tetanic force analysis, motor unit number estimation (MUNE), and wet muscle weights. Animals in both the P5 and P7 nerve injury groups displayed significant neuron loss, and decreased functional recovery following nerve injury, suggesting that severe deficits persist in these animals following nerve injury beyond P5.
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