The in-vitro sciatic nerve model: new Insights into neuropathy

Abstract

Polyneuropathy is a prevalent condition that can severely impair a person’s quality of life.  In-vitro experiments were conducted in order to study external factors associated with polyneuropathy in isolation from systemic effects in live models.  Sciatic nerves were isolated from Sprague-Dawley rats and placed in perfusion chambers that contained artificial cerebral spinal fluid.  The nerves were stimulated, the averaged nerve action potential (NAP) waveforms were digitized, and the NAP amplitude, velocity, duration, and amplitude of the paired pulse response were analyzed.  The effects of anoxia, hypothermia, and external metabolic substrates on the NAP were analyzed.  Results showed a complex interaction between the three categories and their effects on the NAP parameters.  Cyclic episodes of anoxia had different effects on NAP amplitude and velocity, and also resulted in ischemic preconditioning of the nerve, which is perhaps due to the build-up of glycogen during the re-oxygenated (recovery) phases.  Hypothermia appeared to best preserve nerve function when present during the anoxic phases and absent during the recovery phases, perhaps allowing for glycogenolysis during the recovery phases.  The metabolic function of the nerve during intermittent anoxia was then analyzed, and it was determined that hyperglycemia improved ischemic preconditioning while decreasing NAP amplitude overtime, suggesting that there are other contributing processes such as the production of free radicals and advanced glycation end-products.  Lactate uniquely supported the nerve in high and low concentrations during both continuous oxygenation and intermittent anoxia.  The existence of a lactate shuttle between Schwann cells and peripheral nerves may explain these results.  The findings from these in-vitro experiments may be important in future hypothesis testing in search for effective treatment of polyneuropathy.