Polyethylene glycol rapidly restores physiological functions in damaged sciatic nerves of guinea pigs

We have studied the ability of the hydrophilic polymer polyethylene glycol (PEG) to anatomically and physiologically reconnect damaged axons of the adult guinea pig spinal cord. Here we have extended this approach to test whether completely severed guinea pig sciatic nerves in isolation could be fused and whether PEG was able to repair severe standardized crush injuries to sciatic nerves in vivo.

The fusion test was performed with isolated sciatic nerves maintained in a double-sucrose gap recording chamber. For in vivo experiments, the sciatic nerve was surgically exposed in the hind leg of deeply anesthetized adult guinea pigs and was crushed proximal to its insertion in the gastrocnemius muscle. PEG was injected just beneath the epineurium with a 29-gauge needle, allowed to remain in the damaged axon region for 2 minutes, and removed. Sham-treated guinea pigs received an injection of water or Krebs' solution. Three indices of recovery were simultaneously monitored in response to electrical stimulation of the proximal nerve, i.e., 1) recovery of compound muscle action potentials (in millivolts), 2) contraction force of the muscle (in dynes), and 3) displacement of the muscle (in millimeters).

When isolated sciatic nerves were severed within the double-sucrose gap chamber, compound action potential propagation through the transection plane was eliminated. After abutment of the two segments and 2-minute PEG application to this site, variable compound action potential recovery was measured in all four cases. The crush injuries to the sciatic nerve in vivo eliminated the three functional responses to sciatic nerve stimulation in all animals. Within the first 30 minutes after treatment, only 1 of 12 control animals exhibited spontaneous recovery in any of these measures, compared with six of eight PEG-treated animals. By 45 minutes, two more sham-treated animals and one more PEG-treated animal had recovered at least one functional response. This difference in proportions between PEG-treated and sham-treated animals was statistically significant (P < or =0.02).

We conclude that these preliminary data suggest that PEG application may be a way to interfere with the steady dissolution of peripheral nerve fibers after mechanical damage and to even functionally fuse or reconnect severed proximal and distal segments.