TRAUMATIZED RAT STRIATUM PRODUCES NEURITE-PROMOTING AND NEUROTROPHIC ACTIVITIES IN-VITRO

We have previously reported that ciliary neurotrophic factor (CNTF) mR NA is upregulated in the rat striatum following trauma and that its pe ak is coincident with a peak ill the number of GFAP-positive astrocyte s. CNTF, or other neurotrophic factors present in the traumatized stri atum, may be involved in the dopaminergic fiber sprouting seen followi ng cavitation or graft implantation in animal models of Parkinson's di sease. This study was undertaken in order to further characterize the neurotrophic activity present following trauma through the use of bioa ssays. Adult rats underwent stereotaxic biopsy of the right striatum, and gelatin sponge [gelfoam (GF)] was placed in the resultant cavity. GF was collected from 1 to 30 days following trauma and homogenized. G F extracts (with equal protein concentrations) were assayed using dors al root ganglion (DRG) explants, dissociated ciliary ganglia (CG), and human dopaminergic neuroblastoma cell (SH-SY5Y) cultures. The GF extr acts had significant neurite-promoting activity (NPA) for DRG, CG:, an d SH-SY5Y cells, with the maximum effect seen 7 days after trauma. NPA was not blocked by anti-nerve growth factor (NGF) Ab, but anti-brain- derived neurotrophic factor (BDNF) Ab significantly blocked the activi ty for DRG. The GF extracts protected the SH-SY5Y cells from the neuro toxins 6-OHDA and MPP(+), as did NGF and BDNF. This neuroprotective ef fect of GF was not blocked by anti-NGF Ab, This study suggests that th e neurotrophic activity in GF extracts has CNTF-like and BDNF-like com ponents as well as another, undefined component. (C) 1996 Academic Pre ss, Inc.