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Effects of Melatonin on the Cerebellum of Infant Rat Following Kaolin-Induced Hydrocephalus: a Histochemical and Immunohistochemical Study

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Abstract

Hydrocephalus is a developmental disorder causing abnormally collected cerebrospinal fluid within the cerebral ventricles. It leads to bigger skulls and many dysfunctions related to the nervous system. Here, we addressed whether exogenous melatonin administration could reverse the clinical features of kaolin-induced hydrocephalus in infantile rats. A controlled double-blinded study was conducted in 2-week-old 45 Wistar albino rats, which were divided into three groups: Group A, the control group, received intracisternal sham injection with solely the needle insertion; group B, the hydrocephalus group, was treated with isotonic NaCl after kaolin injection; and group C, the hydrocephalus + melatonin group, was given i.p. exogenous melatonin at a dose of 0.5 mg/100 g body weight after kaolin injection. Histological and immunohistochemical analyses were performed after the induction of hydrocephalus and melatonin administration. Glial fibrillary acidic protein was stained by immunohistochemical method. TUNEL method was used to define and quantitate apoptosis in the cerebellar tissues. Statistical analysis was performed by nonparametric Kruskal–Wallis H test, and once significance was determined among means, post hoc pairwise comparisons were carried out using Mann–Whitney U test. We found that melatonin administration significantly ameliorated ratio of substantia grisea area/substantia alba area in the cerebellum of infantile rats. Histologically, there was a significant reduction in the number of cerebellar apoptotic cells after the hydrocephalus induced by kaolin (P < 0.05). Our results clearly revealed that the histopathological changes in the cerebellum were reversed by systemic melatonin administration in infantile rats with kaolin-induced hydrocephalus. Nevertheless, further studies are needed to suggest melatonin as a candidate protective drug in children with hydrocephalus.

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Acknowledgments

Authors would like to thank Erdinç Yılmaz and Sevim Balkız for their excellent technical assistance and N. Ceren Sümer Turanlıgil for linguistic support. Also, we would like to express our great thanks to Professor Dr. Juan F. Martínez-Lage, Professor Dr. Abhaya V. Kulkarni, and Professor Dr. Daniel Cardinali for their critical reading of the manuscript and for their comments on an earlier version of the manuscript, and we sincerely thank the two “anonymous” reviewers for their insight full comments on our manucript. This study was presented in part at the 13th National Congress of Histology and Embryology Society, Cesme, Turkey, April 30-May 3, 2016.

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    Authors and Affiliations

    1. Department of Histology and Embryology, Ege University School of Medicine, Izmir, Turkey

      Yiğit Uyanıkgil & Meral Baka

    2. Cord Blood, Cell-Tissue Research and Application Center, Ege University, Izmir, Turkey

      Yiğit Uyanıkgil & Meral Baka

    3. Department of Neurosurgery, Adnan Menderes University School of Medicine, Aydın, Turkey

      Mehmet Turgut

    4. Cumhuriyet Mahallesi, Adnan Menderes Bulvarı, Haltur Apartmanı, No: 6 Daire: 7, TR-09020, Aydın, Turkey

      Mehmet Turgut

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    1. Yiğit Uyanıkgil
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    Correspondence to Mehmet Turgut.

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    Yiğit Uyanıkgil and Mehmet Turgut contributed equally to this work.

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    Uyanıkgil, Y., Turgut, M. & Baka, M. Effects of Melatonin on the Cerebellum of Infant Rat Following Kaolin-Induced Hydrocephalus: a Histochemical and Immunohistochemical Study. Cerebellum 16, 142–150 (2017). https://doi.org/10.1007/s12311-016-0778-9

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