Induction of activating transcription factor 3 after different sciatic nerve injuries in adult rats.

Staining by activating transcription factor 3 (ATF3), a neuronal marker of nerve injury, was examined by immunocytochemistry in neurons and Schwann cells after crush or transection (regeneration inhibited) of rat sciatic nerve. ATF3 immunoreactivity peaked in neurons after three days and then gradually subsided to normal within 12 weeks after the crush. The response lasted somewhat longer and declined over time in spinal cord neurons but not in those of dorsal root ganglia (DRG) after transection, indicating a differential regulation of sensory and motor neurons. ATF3 expression was more pronounced in Schwann cells, and remained longer after transection, implying that to some extent regenerating axons produce signals that reduce ATF3 expression in Schwann cells. However, even after transection without repair (no contact with regenerating axons), ATF3 expression in Schwann cells in the distal segment decreased over time suggesting that regenerating axons are not entirely responsible for the down-regulation. These findings have clinical implications on when it is worthwhile to reconstruct nerve injuries.