The investigators have described the fusion of transected and abutted guinea pig spinal axons after topical application of the water soluble polymer polyethylene glycol (PEG). They also show that reconstruction of membrane lesions produced by severe compression sufficient to inhibit nerve impulse conduction can be reversed within a few minutes of PEG application, PEG removal, and rehydration. These studies were carried out on strips of isolated guinea pig spinal cord white matter maintained in isolation within a new double sucrose gap-recording chamber. Functional repair was defined by the recovery of the spinal cord to propagate compound action potentials (CAPs) through the compression lesion or former transection plane. Restored anatomical continuity of axons across the transection was determined by the intracellular spread of two fluorescent tracers. Here they propose to evaluate the ability of PEG and PEG derivatives to rapidly repair crushed nerve fibers of the adult guinea pig in situ. They further intend to test PEG derivatives that further reduce nerve fiber destruction (by complexed free radical scavengers) and facilitate nerve impulse conduction (by complexed potassium channel blockers). They will apply a three pronged strategy of evaluation of functional recovery in this in vivo investigation: 1.) Physiological measurements of conduction through the lesion in the intact animal will be carried out using somatosensory evoked potential (SSEP) examination prior to the injury, and this baseline will set the comparison for SSEP recording at various time points subsequent to the injury, 2.) Behavioral recovery will be assessed using a quantitative method involving stop frame video morphometry of the Cutaneous Trunci Muscle (CTM) reflex - a behavioral index of white matter integrity in the guinea pig, and 3.) An anatomical evaluation of the degree of axonal repair between control and PEG treated spinal cords using a horseradish peroxidase dye exclusion test and conventional histology.
