Melatonin protects hippocampal neurons in vivo against kainic acid-induced damage in mice

In this investigation, 40 mg/ kg of the excitatory neurotoxin kainic acid (KA) was subcutaneously administered to CD2-F1 mice. In this mouse strain morphological damage induced by KA in the hippocampus was markedly concentrated in the CA3 pyramidal neurons. Neuronal injury was accompanied by several pathological neurobehavioral activities including arching of tail, tremors and seizures, and by certain biochemical changes, i.e., increased lipid peroxidation products (LPO) in the brain. When melatonin was injected intraperitoneally at a single dose of 5 mg/ kg 10 min before KA administration, it significantly reduced these pathological neurobehavioral changes and almost completely attenuated the increase in LPO and morphological damage induced by KA. The neuroprotective effect of melatonin against KA-induced brain damage in mice is believed to be in part related to its oxygen radical scavenging properties as well as its antiepileptic and GABA receptor regulatory actions. Considering melatonin's relative lack of toxicity and ability to enter the brain, these results along with previous evidence suggest that melatonin, which is a natural substance, may be useful in combating free radical-induced neuronal injury in acute situations such as stroke and brain trauma as well as neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease that have free radicals as causative factors. J. Neurosci. Res. 54:382–389, 1998. © 1998 Wiley-Liss, Inc.