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Neuroprotective Effects of Lacosamide and Memantine on Hyperoxic Brain Injury in Rats

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Abstract

In neonates supraphysiological oxygen therapy has been demonstrated to cause neuronal death in hippocampus, prefrontal cortex, parietal cortex, and retrosplenial cortex. There is a need for the detection of novel neuroprotective drugs. Neuroprotective effects of lacosamide or memantine have been demonstrated in adult patients with ischemia, trauma and status epilepticus. The effects in immature brains may be different. This study aimed to evaluate neuroprotective effects of lacosamide and memantine treatment in a hyperoxia-induced brain injury model in immature rats. This study was performed in the Animal Experiments Laboratory of Dokuz Eylul University Faculty of Medicine. Neonatal Wistar strain rat pups were exposed to hyperoxia (80% oxygen + 20% nitrogen) for five days postnatally. They were divided into five groups; hyperoxia + lacosamide, hyperoxia + memantine, hyperoxia + lacosamide and memantine, hyperoxia + saline, control groups. After termination of the experiment, brain tissues were examined. Neuron counting in examined regions were found to be higher in hyperoxia + memantine and hyperoxia + lacosamide and memantine groups than hyperoxia + saline group. The presence of apoptotic cells evaluated with TUNEL and active Caspase-3 in hyperoxia + memantine and hyperoxia + lacosamide and memantine groups were found to be lower compared to hyperoxia + saline group. This study demonstrates that neuron death and apoptosis in newborn rat brains after hyperoxia is reduced upon memantine treatment. This is the first study to show the effects of memantine and lacosamide on hyperoxia-induced damage in neonatal rat brains.

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Authors and Affiliations

  1. Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey

    İpek Polat, Erhan Bayram, Uluç Yiş, Müge Ayanoğlu, Derya Okur, Pınar Edem, Cem Paketçi & Semra Hız Kurul

  2. Department of Histology and Embryology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey

    Serap Cilaker Mıcılı & Kazım Tuğyan

  3. Department of Laboratory Animal Science, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey

    Meryem Çalışır & Osman Yılmaz

Authors
  1. İpek Polat
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  2. Serap Cilaker Mıcılı
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  3. Meryem Çalışır
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  12. Semra Hız Kurul
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Contributions

All authors contributed to the study conception and design. The study was designed and conceptuilized by İP, UY and SHK. Material preparation, data collection and analysis were performed by İpek Polat, EB, MA, DO, PE, CP. Reproduction of animals, care of animals were done by MÇ and OY. Sacrification was done by İP and MÇ. Histological experiments were done by SCM and KT. The first draft of the manuscript was written by İpek Polat and all authors commented on previous versions of the manuscript. UY and SHK critically reviewed and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to İpek Polat.

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All the authors declare that there is no conflict of interest.

Ethical Approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution. Approval was obtained from the Ethics Committee of Animal Experiments of Dokuz Eylül University Local Ethics Committees (Approval Date/Number: 27.12.2016-71/2016).

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Polat, İ., Cilaker Mıcılı, S., Çalışır, M. et al. Neuroprotective Effects of Lacosamide and Memantine on Hyperoxic Brain Injury in Rats. Neurochem Res 45, 1920–1929 (2020). https://doi.org/10.1007/s11064-020-03056-5

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  • DOI: https://doi.org/10.1007/s11064-020-03056-5

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