NERVE REGENERATION IN PREDEGENERATED BASAL LAMINA GRAFT - THE EFFECT OF DURATION OF PREDEGENERATION ON AXONAL EXTENSION

We used predegenerated acellular grafts to bridge proximal and distal stumps of transected nerves and studied how the duration of predegener ation might affect axonal regeneration. Predegenerated acellular graft s were prepared by transecting the tibial nerve of donor rats and, aft er a period of degeneration, freeze-thawing a 40-mm long segment of th e distal stump. Five degeneration periods were used: 0 days (for fresh grafts), 3 days, 1 week, 4 weeks, and 8 weeks. Fresh cellular grafts not treated with freeze-thawing were also used for comparison. Each gr aft was then transplanted to an isogeneic recipient rat, in which it w as used to bridge the proximal stump of the transected left tibial ner ve and the distal stump of the transected right tibial nerve. Six week s were allowed for the regeneration of axons in all grafts. The regene ration was then assessed by studying transverse sections of the grafts , to determine the maximum length that the axons had regenerated, and the packing density of axons (percentage of sampled areas occupied by axons). The results show that axons had grown to the maximum length in the Li-week predegenerated grafts, and had the highest packing densit y in the 1-week predegenerated grafts. Regeneration in the fresh acell ular (0-day predegenerated) and 8-week predegenerated grafts, especial ly the latter, was poor. We examine the results with reference to time dependent events of Wallerian degeneration and propose that there are beneficial effects of multiple factors on the grafts during the first 4 weeks of predegeneration, causing a slow but significant improvemen t in their capability to support axonal growth. The subsequent rapid d eterioration of such capability may be related to structural changes i n the extracellular scaffold. (C) 1994 Academic Press, Inc.