Glial cell line-derived neurotrophic factor protects against delayed neuronal death after transient forebrain ischemia in rats

Glial cell line-derived neurotrophic factor, a member of the transforming g rowth factor-p superfamily, is a potent neurotrophic factor, which has a va riety of biological activities that affect several types of neurons in both the central and peripheral nervous systems. In this study, we examined the effects of glial cell line-derived neurotrophic factor on delayed neuronal death in the hippocampal CA1 region of rats after transient forebrain isch emia, In the control rats pretreated with the vehicle, transient forebrain ischemia-induced delayed neuronal death in the hippocampal CA1 region was o bserved seven days after reperfusion, Pretreatment with glial cell line-der ived neurotrophic factor (1.0 mu g), which was directly microinjected into the right hippocampal CA1 region, gave significant protection against the d elayed hippocampal neuronal death. On the contralateral side of the hippoca mpus, which was not injected with glial cell line-derived neurotrophic fact or, delayed neuronal death similar to that seen in vehicle-treated control animals was observed. Intracerebroventricular glial cell line-derived neuro trophic factor (2.5 mu g) injection also protected against delayed neuronal death. In addition, pretreatment with glial cell line-derived neurotrophic factor gave significant protection against apoptotic cell death induced by brain ischemia in the hippocampal CA1 region, as determined by in situ sta ining for DNA fragmentation. These findings suggest that glial cell line-derived neurotrophic factor pla ys an important role in delayed neuronal death induced by brain ischemia. ( C) 1999 IBRO. Published by Elsevier Science Ltd.