Electrophysiological study of conditioning lesion effect on rat sciatic nerve regeneration following either prior section or freeze. I. Intensity and time course

Abstract

A peripheral nerve lesion performed distally prior to a proximal axotomy is known to result in an increase in the rate of regeneration of both sensory and motor fibres. This phenomenon is called the ‘conditioning lesion effect’. The aim of this study was to determine whether or not the kind of the conditioning lesion influences the intensity and the time course of the conditioning lesion effect. The prior lesion was performed on the tibial nerve of rats at the ankle either by cutting the nerve of freezing it by means of a 1 mm diameter liquid nitrogen cryod. At several points in time up to 28 days a second (or test) lesion consisting of a freeze was performed on the sciatic nerve at the middle part of the thigh. The regeneration of the fastest growing fibres of the sciatic nerve was measured electrophysiologically 5, 7 and 9 days after the test lesion. The nerve was surgically removed, immediately mounted in a recording nerve chamber and stimulated proximally to the test lesion. The distance between the test lesion and the most distal point where an evoked nerve potential was detectable was taken as the regenerated nerve length. Then the rate of regeneration was calculated and the initial delay was estimated by means of a linear regression plotting the regenerated nerve lengths against the days of recording. All the results were compared to those of a control group where the test lesion alone was performed. The increase in the maximal rate of regeneration was greater following a prior section (+25%) than following a prior freeze (+12%). Following a prior section, the rate of regeneration began to be significantly increased for a conditioning interval of 4 days, and went on until a conditioning interval of 28 days. By contrast, after a prior freeze the rate of regeneration was significantly increased solely for an interval of 14 days. Following a prior freeze, the estimated initial delay was more decreased (from 2.59 ± 0.08 days to 1.45 ± 0.20 days for a conditioning interval of 7 days) than following a section (from 2.59 ± 0.08 days to 2.01 ± 0.15 days for a conditioning interval of 4 days). These results showed the following differences between the conditioning effects of a prior section and a prior freeze: (1) greater duration and amplitude of the enhancement of the rate of regeneration following a prior section; and (2) greater reduction in the initial delay after a prior freeze. The respective roles played by the intrinsic regulation of the conditioning lesion effect and by non-neuronal cells is discussed.