Synergistic lithium chloride and glial cell line-derived neurotrophic factor delivery for peripheral nerve repair in a rodent sciatic nerve injury model.

Background: Restoring peripheral nerve function after long gap peripheral nerve damage is challenging. Lithium chloride has demonstrated neuroprotective qualities and therefore shows great potential therapeutic benefit for some neurodegenerative diseases. This study examined the synergistic combination of glial cell line-derived neurotrophic factor and lithium chloride and its effect on peripheral nerve regeneration in a rat sciatic nerve injury model. Methods: Polycaprolactone conduits with glial cell line-derived neurotrophic factor-loaded double-walled microspheres and local injections of lithium chloride, 1.5 or 2.5 mEq/kg body weight, were examined in a 15-mm rat sciatic nerve defect model. Eighteen Lewis male rats were divided randomly into control, 1.5-, and 2.5-mEq/kg lithium chloride injection groups. As an indicator of recovery, nerve sections were stained with S100, protein gene product 9.5 antibody, and toluidine blue. Results: Nerves stained with S100 and protein gene product 9.5 antibody demonstrated a significantly increased density of Schwann cells and axons in the 2.5-mEq/kg lithium chloride injection-treated groups compared with both the control and 1.5-mEq/kg lithium chloride injection-treated groups (p < 0.05). At 6 weeks, histomorphometry revealed a significantly higher fiber density in the middle of the conduit for the 2.5-mEq/kg groups compared with the 1.5-mEq/kg group or the control group. Conclusion: Polycaprolactone nerve guides with glial cell line-derived neurotrophic factor-loaded double-walled microspheres and local injections of lithium chloride, 2.5-mEq/kg, represent a potentially viable guiding material for Schwann cell and axon migration and proliferation for the treatment of peripheral nerve regeneration.