Phospholipase A2 activity is required for regeneration of sensory axons in cultured adult sciatic nerves

The adult frog dorsal root ganglia (DRGs) and their sciatic nerves (ScN) survive in organ culture for several days. About 3 days after a local test crush, the sensory axons start to regenerate into the distal nerve stump at a rate of approximately 0.6-0.9 mm/day. The axonal outgrowth is inhibited in a non-toxic way by low concentrations of three different phospholipase A2 (PLA₂) inhibitors: 4-bromophenacyl bromide (BPB), aristolochic acid, and oleyl-oxyethyl-phosphoryl-choline (OOPC). In contrast, the outgrowth was slightly stimulated by 0.2 μM melittin, a PLA₂ activator. Most experiments refer to the effects of BPB, which was shown to almost completely inhibit outgrowth at a concentration which did not affect either ganglionic protein synthesis or axonal transport. Using a compartmental system it could clearly be shown that BPB exerted its action in the outgrowth region. Other experiments showed that the initial period (about 3 days), which precedes the outgrowth, was unaffected by BPB. Several structures, including axonal ones, showed immunoreactivity for the low molecular form of PLA₂ (sPLA₂). The results suggest that PLA₂ activity plays an important role in nerve regeneration and exerts its action at a local level, where the growth cones move forward.