Time course of the conditioning lesion effect on axonal regeneration.

Severed axons regenerate more rapidly if they have been injured by a suitably timed earlier axotomy (reviewed in ref. 6). This beneficial 'conditioning lesion effect '17 has been found in mammalian sensory 17 and motor 12 axons, and in the goldfish optic nerve 15. In most studies, conditioning lesions have preceded the testing lesion by 2 weeks ~,8,12,13,15-17,21. However, in one study using a different paradigm (axonal sprouting in the hippocampus), a positive effect was seen when the conditioning lesion preceded the testing lesion by as little as 4 days 18. We have examined the effect of varying the conditioning interval (the time between conditioning and testing lesions) on the regeneration of sensory axons in the rat sciatic nerve in an effort to determine the range of conditioning intervals which are followed by enhanced axonal outgrowth. Knowing the time course of the conditioning effect may have some clinical value, since one reason for delaying the surgical repair of severed peripheral nerves is in order to take advantage of the conditioning lesion effect 4,14, and because a conditioning lesion may be used to facilitate the reinnervation of transplanted muscles 8. For the group with conditioning lesions, male Sprague-Dawley rats (200-350 g) were anesthetized (40 mg/kg pentobarbital plus 160 mg/kg chloral hydrate) and the tibial nerve near the ankle was exposed, cut and ligated with nylon suture. Control animals received a sham operation: the nerve was exposed and gently mobilized but not cut or ligated ~7. The testing lesions were made 1, 4, 7, 14 or 28 days later (as described in ref. 1) by crushing the sciatic nerve where it passes over the fused external obturator and gemelli tendons at the hip joint, using plastic covered jeweler's forceps to deliver two 30 sec crushes. The crush site was marked with black 10-0 nylon suture. The distance between the conditioning and testing lesions averaged 42.4 :k 0.4 (S.E.M.) ram. After both operations the wounds were flushed with saline and closed