SR 57746A ATTENUATES CYTOSTATIC DRUG-INDUCED REDUCTION OF NEURITE OUTGROWTH IN COCULTURES OF RAT DORSAL-ROOT GANGLIA AND SCHWANN-CELLS

A co-culture system of intact rat dorsal root ganglia (DRG) with Schwa nn cells was used to evaluate the potential neurotrophic activity of S R 57746A. Neuritogenesis from DRG was measured with an image analysis system following exposure to different concentrations of SR 57746A. Ne urite outgrowth of intact DRG was increased by SR 57746A and this was more obvious in the presence of co-cultured Schwann cells. The neuropr otective properties of SR 57746A were studied in co-cultures of DRG an d Schwann cells, in which neuritogenesis was reduced by the cytostatic drugs cisplatin, vincristine and taxol. It was found that neurite out growth from DRG treated with cisplatin (3 mu g/ml) and 10 mu M SR 5774 6A for 3 days was significantly higher than after treatment with cispl atin alone. Similarly neuritogenesis from DRG treated with taxol (0.01 mu g/ml) or vincristine (0.5 ng/ml) in combination with 10 mu M SR 57 746A was significantly increased compared to treatment with taxol or v incristine alone. When intact DRG were incubated in vitro with 3 mu g/ ml cisplatin and without Schwann cells, 10 mu M SR 57746A also had a n europrotective effect. These data suggest that SR 57746A has neuroprot ective potential and that this effect does not depend solely on the pr esence of Schwann cells.