Melatonin reduces cerebral edema formation caused by transient forebrain ischemia in rats Takashi Kondoh a , Hisayuki Uneyama a , Hitoo Nishino b , Kunio Torii a, * a Institute of Life Sciences, Ajinomoto Co., Inc., Suzuki-cho 1-1, Kawasaki-ku, Kawasaki 210-8681, Japan b Department of Physiology, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan Abstract Reduction of cerebral edema, an early symptom of ischemia, is one of the most important remedies for reducing subsequent chronic neural damage in stroke. Melatonin, a metabolite of tryptophan released from the pineal gland, has been found to be effective against neurotoxicity in vitro. The present study was aimed to demonstrate the effectiveness of melatonin in vivo in reducing ischemia-induced edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.): just prior to 1 h MCA occlusion and 1 day after the surgery. T 2 -weighted multislice spin- echo images were acquired 1 day after the surgery. Increases in T 2 -weighted signals in ischemic sites of the brain were clearly observed after MCA occlusion. The signal increase was found mainly in the striatum and in the cerebral cortex in saline-treated control rats. In the melatonin-treated group, the total volume of cerebral edema was reduced by 45.3% compared to control group ( P < 0.01). The protective effect of melatonin against cerebral edema was more clearly observed in the cerebral cortex (reduced by 56.1%, P < 0.01), while the reduction of edema volume in the striatum was weak (reduced by 23.0%). The present MRI study clearly demonstrated that melatonin is effective in reducing edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments. D 2002 Elsevier Science Inc. All rights reserved. Keywords: Melatonin; Ischemia; Stroke; Middle cerebral artery occlusion; Reperfusion; Cerebral edema; Cerebral cortex; Striatum; MRI; T 2 -weighted image; Rat 0024-3205/02/$ - see front matter D 2002 Elsevier Science Inc. All rights reserved. PII:S0024-3205(02)02256-7 * Corresponding author. Tel.: +81-44-244-7183; fax: +81-44-210-5893. E-mail address: kunio _ torii@ajinomoto.com (K. Torii). www.elsevier.com/locate/lifescie Life Sciences 72 (2002) 583 – 590