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Neuropharmacology And Neurotoxicology

Caffeine-induced neuronal death in neonatal rat brain and cortical cell cultures

Kang, Sang Hwan1 3; Ae Lee, Young1 3; Won, Seok Joon1 3; Rhee, Ki-Hyeong4; Gwag, Byoung Joo1 2 3 CA

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We examined the potential neurotoxicity of caffeine in vivo and in vitro. Intraperitoneal administration of caffeine (50 mg/kg, 3 times a day) produced neuronal death in various brain areas of neonatal rats 24 h later. Caffeine at doses > 300 μM was also neurotoxic in murine cortical cell cultures. Caffeine-induced neuronal death was accompanied by cell body shrinkage and attenuated by anti-apoptotic drugs including cycloheximide, high potassium, and growth factors. Two necrotic pathways, excitotoxicity and oxidative stress, did not mediate caffeine neurotoxicity. The pro-apoptotic protease caspase-3 was activated to mediate neuronal death following exposure to caffeine. The present findings suggest that caffeine may cause caspase-3-dependent neuronal cell apoptosis in neonatal rat as well as in vitro.

© 2002 Lippincott Williams & Wilkins, Inc.


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