Acceleration of Axonal Outgrowth in Motor Axons from Mature and Old F344 Rats after a Conditioning Lesion

Abstract

The conditioning lesion paradigm has proven to be a very useful model in which to examine the mechanisms of axonal outgrowth after injury. In the present study, we have used the conditioning lesion model to examine the ability of motor axons from mature (6–8 months) and old (22–24 months) Fischer 344 rats to form new axonal sprouts. We show that after a single lesion (sham-conditioned axons followed by a testing lesion), axonal outgrowth rates are slower at earlier vs longer postlesion times in mature rats: between 4 and 8 days postlesion, outgrowth rates are 2.4 ± 0.4 mm/day, whereas between 8 and 11 days postlesion outgrowth rates are 4.6 ± 0.7 mm/day. After a single lesion in the old rat, at early postlesion times, the axonal outgrowth rate is 1.9 ± 0.4 mm/day but with increasing time after injury, outgrowth rates slow down to 1.1 ± 0.8 mm/day. In conditioned motor axons from mature rats, outgrowth rates increase from 3.1 ± 0.4 mm/day at early postlesion times to 5.2 ± 0.6 mm/day at longer postlesion times. An even more dramatic increase in outgrowth rate is seen in conditioned axons from old rats: 2.4 ± 0.4 mm/day at early postlesion times to 6.3 ± 1.0 mm/day at later times after lesion. There is no change in the initial delay before sprouting under any condition. These data support the hypothesis that axons from old animals can be stimulated to repair themselves at rates comparable to those seen in younger animals and suggest that there may be an absolute maximum outgrowth rate attainable by newly forming axon sprouts.