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Article type: Research Article
Authors: Ozyener, Fadil | Çetinkaya, Merih | Alkan, Tulin | Gören, Bülent | Kafa, Ilker Mustafa | Kurt, Mustafa Ayberk | Koksal, Nilgun
Affiliations: Faculty of Medicine, Department of Physiology, Uludag University, Bursa, Turkey | Faculty of Medicine, Department of Pediatrics, Division of Neonatology, Uludag University, Bursa, Turkey | Faculty of Medicine, Department of Anatomy, Uludag University, Bursa, Turkey
Note: [] Corresponding author: Merih Çetinkaya, MD, PhD, Uludağ Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları AD, 16059, Görükle, Bursa, Turkey. Tel.: +90 224 2950447; Fax: +90 224 4428143; E-mail: drmerih@yahoo.com
Abstract: Purpose: The objective of this study was to compare the effects of two neuroprotective agents; melatonin, a free radical scavenger and topiramate, AMPA/kainate receptor antagonist, administered alone or in combination in neonatal hypoxic-ischemic model. Methods: After being anesthetized, 7-day-old pups underwent ischemia followed by exposure to hypoxia. The pups were divided into 4 groups in order to receive the vehicle, melatonin, topiramate and combination of topiramate and melatonin. These were administered intraperitoneally for three times; the first before ischemia, the second after hypoxia and the third 24 hours after the second dose. After sacrification, infarct volume and apoptosis were evaluated. Results: Percent infarcted brain volume was significantly reduced in rats which received drugs compared with those which received the vehicle. The number of TUNEL positive cells per unit area in hippocampus and cortex were markedly reduced in drug treated groups compared with control group. No significant differences were found regarding percent infarcted brain volume and number of TUNEL positive cells among drug-treated groups. Conclusions: Melatonin and topiramate, administered either alone or in combination significantly reduced the percent infarcted brain volume and number of TUNEL positive cells suggesting that these agents may confer benefit in treatment of infants with hypoxic-ischemic encephalopathy.
Keywords: Combination therapy, hypoxia-ischemia, melatonin, neuroprotection, topiramate
DOI: 10.3233/RNN-2012-120217
Journal: Restorative Neurology and Neuroscience, vol. 30, no. 5, pp. 435-444, 2012
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