Abstract

A prior “conditioning” lesion enhances the rate of nerve regeneration after a subsequent “test” lesion made proximal to the first injury. This effect has been observed in several species and in both peripheral and central neurons. Nonetheless, the molecular basis of the conditioning effect remains uncertain. The initiation of regeneration and its progress appear to depend on separate processes, and either or both may be affected in different species. This investigation focused on rat sciatic nerve, where only the rate of elongation appears to be consistently enhanced. I investigated the distribution of adenylate cyclase activity in various segments of the injured nerves to determine if cyclic AMP might modulate some aspect of the regeneration process. Adenylate cyclase activity accumulated at the point of injury and was significantly increased in regenerating nerve tips, as determined by the pinch test, in both condition/test- and test-lesion nerves. The sole significant difference between these experimental groups was an increase in adenylate cyclase activity immediately distal to the test lesion and immediately distal to the regeneration point in the condition-lesion nerves. I suggest that an increase in cyclic AMP concentration in nerve segments distal to a lesion may condition the local environment to enhance axon sprouting or elongation. Nerve growth stimulated by a local increase in cyclic AMP, however, may require additional cell body-supplied material to be sustained.

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