Ciliary neurotrophic factor protects hippocampal neurons from excitotoxic damage

The loss of neurons is responsible for many acute neurological disorders as well as chronic neurodegenerative diseases. This cell loss might be prevented by a direct delivery of neurotrophic factors. Therefore, we investigated the capacity of ciliary neurotrophic factor (CNTF) and nerve growth factor (NGF) as well as the combination of both growth factors on the glutamate-induced excitotoxic damage in hippocampal cultures. The exposure of hippocampal neuronal/glial co-cultures to 0.5 mM L-glutamate for 1 h induced pronounced neurotoxicity evaluated 18 h later by trypan blue staining and morphological criteria. The damaged neurons showed both apoptotic and necrotic features. However, CNTF (1-1000 pg/ml) reduced neuronal degeneration when administered 6 and 24 h before induction of injury and remained in contact with the cells until evaluation of neuronal damage. Furthermore, NGF (1 ng/ml) also rescued the hippocampal neurons under the same experimental conditions and with a similar to CNTF potency. However, the co-administration of NGF and CNTF (but not either factor alone) restored the neuronal survival to control levels. Our results support the hypothesis that administering neurotrophic factors could represent an alternative strategy for the treatment of acute and chronic brain disorders. (C) 1999 Elsevier Science Ltd. All rights reserved.