UP-REGULATION OF NERVE GROWTH-FACTOR FOLLOWING CORTICAL TRAUMA

As part of the inflammatory response to brain injury, CSF and tissue l evels of interleukin-1 beta (IL-1 beta) are elevated after trauma. Thi s elevation in IL-1 beta initiates a cascade of events among which may be an upregulation in nerve growth factor (NGF) in brain tissue. We i nfused IL-1 beta into the ventricle of adult rats and found a two- to fourfold increase in NGF in the cerebral cortex, hippocampus, and cere bellum, suggesting that IL-1 beta induced in vivo may also increase NG F in the brain. To test this hypothesis we utilized two models of trau matic brain injury (TBI) in the rat and examined NGF protein and RNA i n the cortex over a period of several days. Both weight drop and contr olled cortical contusion models of CNS trauma demonstrated large and s ignificant increases in NGF protein in the cortex. NGF RNA was assesse d in the controlled cortical contusion model and increased approximate ly fivefold by 1 day post-trauma. The remarkable elevation of NGF obse rved following TBI suggests that its role in response to injury may be other than as a target derived growth substance. We hypothesize that the elevation of NGF in trauma induces upregulation of enzymes which s uppress free-radical formation after injury. (C) 1994 Academic Press, Inc.