ASTROCYTES ARE THE MAJOR SOURCE OF NERVE GROWTH-FACTOR UP-REGULATION FOLLOWING TRAUMATIC BRAIN INJURY IN THE RAT

Previous studies from our group have demonstrated an upregulation in n erve growth factor (NGF) RNA and protein in the cortex 24 h following traumatic brain injury (TBI) in a rat model. This increase in NGF is s uppressed if rats are subjected to 4 h of whole-body hypothermia follo wing TBI. In the present study we used in situ hybridization to extend our initial RNA gel-blot (Northern) hybridization findings by demonst rating that NGF RNA is increased in the cortex following TBI and that hypothermia diminishes this response. Further, by combining in situ hy bridization with immunocytochemistry for glial fibrillary acidic prote in we demonstrate that astrocytes are the major cellular source for th e upregulation in NGF and that this upregulation can be observed in th e hippocampus as early as 3 h posttrauma. The predominantly astrocytic origin suggests that the NGF upregulation is not related primarily to cholinotrophic activities. We hypothesize that its function is to sti mulate upregulation of antioxidant enzymes, as part of an injury-induc ed cascade, and that supplementation of NGF or antioxidants may be war ranted in hypothermic therapies for head injury. (C) 1998 Academic Pre ss.