Trophic factor modulation of c-Jun expression in supraspinal neurons after chronic spinal cord injury.

Abstract

Cervical, but not thoracic spinal cord injury upregulates, in certain brainstem neurons, the expression of c-Jun, an inducible transcription factor that 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 long period after spinal cord injury and to determine if such expression could be influenced by trophic or growth factors. Adult rats received a cervical (C3) hemisection lesion. Four or eight weeks later the lesion site was exposed, scar tissue in the cavity was removed and gel foam saturated with ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (FGF2), or phosphate-buffered saline (PBS) as a control was placed into the cavity. Animals were sacrificed 7 days after treatment. In response to axotomy, c-Jun expression remained elevated in the red nucleus (RN) and vestibular complex (VST) at 4 weeks after injury, with no changes observed following scar tissue removal and PBS treatment. In contrast, treatment with CNTF further increased expression by RN neurons, but not VST neurons. Treatment with FGF2 had no significant effect on c-Jun expression at 4 weeks after injury. After 8 weeks, c-Jun expression approached baseline levels; however, removal of scar tissue, with subsequent secondary injury, caused an upregulation of c-Jun expression in both RN and VST neurons, which could be enhanced by CNTF, but not FGF2, treatment. At long postinjury intervals, interventive therapy known to promote axonal regeneration from chronically injured neurons leads 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.