Damaged peripheral nerves generally regenerate only a fraction of lost motor and sensory function. In this study, traumatic injury to the sciatic nerve of rats was performed to understand the degeneration and subsequent regeneration processes. The study used a focal demyelination model in conjunction with a nerve-crush injury model to observe the role of the extracellular matrix (ECM) in the regenerative process. The focal demyelination model used lysophosphatidylcholine (LPC) to demyelinate the nerve bundle. This allowed for measuring regeneration rates with the ECM intact. The nerve-crush model caused demyelination through ECM degeneration. Demyelination upregulates nerve growth factor receptors (NGFR), which are essential for the repair and regeneration of nerves and are rarely found in a healthy peripheral nervous system. A local application of nerve growth factor (NGF) was added to half the rats in each model. The models were also combined, which allowed us to determine if applying LPC to a crushed nerve increased the healing rates of the nerve through an additional increase in NGFRs from the LPC.
The focal demyelination model received a 10 microliter intraneural injection of LPC. The crush model received a 2 mm crush, 30 mm from the dorsal root ganglia, performed with forceps held tightly on the nerve for 30 seconds. The rats that received NGF received a 10 microliter intraneural injection of NGF one week after the initial LPC injection and/or crush. The rats were euthanized either at 3 weeks or 6 weeks after initial LPC injection and/or crush and the nerves removed. The nerves were examined both qualitatively using SEM and immunohistochemistry, and quantitatively using transdermal local electrophysiology.
The addition of NGF allowed us to test the effectiveness of NGF in regeneration. This provided a comparison for our LPC and crush group receiving NGF to determine the effectiveness of combining the two models. It was found that the addition of NGF increased the rate of nerve regeneration in each model. The combined model showed that applying LPC to crushed nerves followed by NGF regenerated faster than crushed nerves receiving NGF.
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