INTRAVENOUS COPOLYMER SURFACTANT P188 ACCELERATES POST-AXONOTEMETIC NEURONAL REGENERATION
Hannes Prescher, MD, Raphael Lee, MD.
University of Chicago, Chicago, IL, USA.
Purpose: Peripheral nerve injury is caused by a sequence of molecular events that is triggered by damage to the cell membrane. Poloxamer 188 (P188), a tri-block copolymer surfactant, has been shown to seal damaged cell membranes and improve cell survival. Here, we investigate if P188 can accelerate recovery after a peripheral nerve injury using an established axonotemetic model.
Methods: A crush injury was performed on the sciatic nerve of ten female Sprague-Dawley rats. Rats were randomized to receive either P188 or dextran, administered intravenously 1 hour after crush injury. Compound nerve action potentials (CNAP) and density of neurofilaments distal to the point of injury were analyzed on post-crush day (PCD) #4, #14, and #21. Values were normalized to the non-operative contralateral control for each animal.
Results: A significant improvement in axonal conduction for animals treated with P188 was observed for PCD#4 and #14 (p<0.01). The segment of axon distal to the site of injury in the P188 treated group demonstrated significant increase in nerve fiber density on PCD#4 (p<0.01).
Conclusion: A single dose of intravenous P188 administered 1 hour after crush injury to rat sciatic nerve resulted in more rapid structural and functional nerve recovery. By targeting damaged cell membranes to limit downstream events that lead to axonal degeneration, P188 may present a novel approach to treating peripheral nerve injury.
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