Selective inhibition of early axonal regeneration by myelin-associated glycoprotein

When the distal stump of a transected peripheral nerve is brought into the vicinity of the proximal nerve stump, the regenerating axons advance toward it across the gap. Similar results are obtained when a predegenerated nerve segment is used. However, when a nerve segment subjected to proximal axotomy 7 days earlier (7-day nerve segment) was placed close to the proximal end of a freshly cut nerve at a distance of less than 1.5 mm, there were neither regenerating axons nor sprouts. The same inhibition of axonal regeneration was also exhibited when a nerve segment subjected to axotomy 9 to 14 days earlier was used. To examine the inhibitory effect of the nerve segments on established regenerating axons, we positioned a 7-day nerve segment in close apposition to a proximal nerve end at 2 or 3 days after transection. The growth of the 3-day-old regenerating axons, already ensheathed by Schwann cells, was not disturbed, but the 2-day-old regenerating axons, consisting of naked axons, were eliminated by the 7-day nerve segment. It is assumed that the findings reflect a mechanism serving to eliminate abundant sprouts and immature axons, probably conferring optimum regeneration and maturation of outgrowing pioneer axons. The inhibitory effect on abundant sprouts and immature axons was completely blocked by local application of antibodies to myelin-associated glycoprotein (MAG). The MAG-containing cells appeared at 6 to 12 days after axotomy.