Acute repair of crushed guinea pig spinal cord by polyethylene glycol. We have studied the responses of adult guinea pig spinal cord white matter to a standardized compression within a sucrose gap recording chamber. This injury eliminated compound action potential (CAP) conduction through the lesion, followed by little or no recovery of conduction by 1 h postinjury. We tested the ability of polyethylene glycol (PEG) to repair the injured axons and restore physiological function. Local application of PEG (1,800 MW, 50% by weight in water) for approximately 2 min restored CAP conduction through the injury as early as 1 min post PEG application. The recovery of the CAP </=1 h was significantly greater in treated compared with control spinal cords (controls = 3.6% of the preinjury amplitude; PEG treated = 19%; P < 0.0001, unpaired Student's t-test). Stimulus-response analysis indicated that the susceptibility for recovery was similar for all calibers of axons after PEG application. The enhanced recovery of conduction after PEG treatment was associated with an early alteration in conduction properties relative to control spinal cords. This included increased refractoriness and sensitivity to potassium channel blockade using 4-aminopyridine (4-AP). Normally 4-AP enhanced the amplitude of the recovering CAPs by approximately 40% in control spinal cords; however this effect was nearly doubled to approximately 72% in PEG treated spinal cords. Because severe clinical injuries to the spinal cord (and some peripheral nerves) are both resistant to medical treatment and usually produced by compression, we discuss the possible clinical benefits of PEG application.