Traumatized rat striatum produces neurite-promoting and neurotrophic activities in vitro

Abstract

We have previously reported that ciliary neurotrophic factor (CNTF) mRNA is upregulated in the rat striatum following trauma and that its peak is coincident with a peak in the number of GFAP-positive astrocytes. CNTF, or other neurotrophic factors present in the traumatized striatum, may be involved in the dopaminergic fiber sprouting seen following cavitation or graft implantation in animal models of Parkinson's disease. This study was undertaken in order to further characterize the neurotrophic activity present following trauma through the use of bioassays. 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. GF extracts (with equal protein concentrations) were assayed using dorsal root ganglion (DRG) explants, dissociated ciliary ganglia (CG), and human dopaminergic neuroblastoma cell (SH-SY5Y) cultures. The GF extracts had significant neurite-promoting activity (NPA) for DRG, CG, and 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 activity for DRG. The GF extracts protected the SH-SY5Y cells from the neurotoxins 6-OHDA and MPP+, as did NGF and BDNF. This neuroprotective effect of GF was not blocked by anti-NGF Ab. This study suggests that the neurotrophic activity in GF extracts has CNTF-like and BDNF-like components as well as another, undefined component.