IMAGE-ANALYSIS OF NEURITIC REGENERATION BY ADULT-RAT DORSAL-ROOT GANGLION NEURONS IN CULTURE - QUANTIFICATION OF THE NEUROTOXICITY OF ANTICANCER AGENTS AND OF ITS PREVENTION BY NERVE GROWTH-FACTOR OR BASIC FIBROBLAST GROWTH-FACTOR BUT NOT BRAIN-DERIVED NEUROTROPHIC FACTOR OR NEUROTROPHIN-3

Peripheral neuropathies are a common side effect of chemotherapeutic a gents, particularly antineoplastic drugs such as taxol, cisplatin, or vinca-alkaloids (vincristine, vinblastine, vindesine). Using dissociat ed cultures of adult rat dorsal root ganglion (DRG) neurons and video image analysis after neurofilament immunostaining, we have designed a system that allows: (i) rapid screening of potential neurotoxic agents , with the establishment of dose-response curves and the calculation o f IC50; (ii) quantification of neurotrophic effects; and (iii) demonst ration of neuroprotection by trophic factors. In particular, we show t hat nerve growth factor (NGF) and basic fibroblast growth factor (bFGF ) stimulate in vitro neuritic regeneration by adult rat DRG neurons, w hile brain-derived neurotrophic factor and neurotrophin-3 lack such ef fects. Furthermore, 24 h of pretreatment by NGF or bFGF drastically de creases the neurotoxic effect of vincristine and cisplatin.