Trophic factor modulation of c-Jun expression in supraspinal neurons afterchronic spinal cord injury

Cervical, but not thoracic spinal cord injury upregulates, in certain brain stem neurons, the expression of c-Jun, an inducible transcription factor th at may be involved in the regenerative program/cell body response to injury . This study was designed to evaluate changes in c-Jun expression over a lo ng period after spinal cord injury and to determine if such expression coul d be influenced by trophic or growth factors. Adult rats received a cervica l (C3) hemisection lesion. Four or eight weeks later the lesion site was ex posed, scar tissue in the cavity was removed and gel foam saturated with ci liary neurotrophic factor (CNTF), basic fibroblast growth factor (FGF2), or phosphate-buffered saline (PBS) as a control was placed into the cavity. A nimals were sacrificed 7 days after treatment. In response to axotomy, c-Ju n expression remained elevated in the red nucleus (RN) and vestibular compl ex (VST) at 4 weeks after injury, with no changes observed following scar t issue removal and PBS treatment. In contrast, treatment with CNTF further i ncreased expression by RN neurons, but not VST neurons. Treatment with FGF2 had no significant effect on c-Jun expression at 4 weeks after injury. Aft er 8 weeks, c-Jun expression approached baseline levels; however, removal o f scar tissue, with subsequent secondary injury, caused an upregulation of c-Jun expression in both RN and VST neurons, which could be enhanced by CNT F, but not FGF2, treatment. At long postinjury intervals, interventive ther apy known to promote axonal regeneration from chronically injured neurons l eads to a reinduction of c-Jun expression. This reinduction may be related to the initiation of the regenerative effort of these neurons, although the lack of c-Jun upregulation by certain types of neurons does not appear to prevent a regenerative response by these cells. (C) 1998 Academic Press.