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Impact of cisplatin administration on cerebellar cortical structure and locomotor activity of infantile and juvenile albino rats: the role of oxidative stress

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Abstract

The central neurotoxicity of cisplatin (CisPt) has always raised questions especially during development, but few studies are available. Hence, this work was designed to assess the CisPt’s impacts on the postnatal rat cerebellum via evaluation of locomotor activity, histological and immunohistochemical studies, and to focus on cerebellar oxidative stress-related alterations. Eighty newborn pups were divided into 2 equal experimental groups: the control group was kept without any treatment and CisPt-treated group received a single subcutaneous injection of CisPt (5 μg /g b.w.) in their nape at PD10. Ten rats at PD11, PD17, and PD30 ages were weighed, then deeply anesthetized and sacrificed. For locomotor assessment, 20 pups were divided equally into control and CisPt-treated groups and tested at PD11-13, PD15-17, and PD28-30 ages. CisPt-treated rats suffered from decreased motor activity and showed decreased body and cerebellar weights, reduced levels of enzymatic antioxidants (SOD and CAT), and non-enzymatic antioxidant defense (GSH), and increase of lipid peroxidation marker (MDA). Histopathologically, CisPt sowed deleterious changes within cerebellar cortical layers in the form of vacuolations, decreased thickness, and hemorrhage (in PD17), while Purkinje cells exhibited profound degenerative changes in the form of swelling, disrupted arrangement, distortion, and nuclear shrinkage. In CisPt-treated rats, GFAP demonstrated upregulated, hypertrophied, and branched Bergmann glial fibers and reactive astrogliosis. Immuno-localization of Ki-67-positive cells revealed defective migration associated with decreased proliferation in early ages in addition to glial proliferation in PD30. In conclusion, CisPt causes oxidative stress-related deleterious effects on structure of developing cerebellar cortex and affects locomotor activity.

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  1. Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

    Hanan E. L. Mokhtar, Mohey A. E. Hulail, Samar Mortada Mahmoud & Doaa Mohammed Yousef

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  1. Hanan E. L. Mokhtar
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Mokhtar, H.E.L., Hulail, M.A.E., Mahmoud, S.M. et al. Impact of cisplatin administration on cerebellar cortical structure and locomotor activity of infantile and juvenile albino rats: the role of oxidative stress. Anat Sci Int 97, 30–47 (2022). https://doi.org/10.1007/s12565-021-00624-9

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  • DOI: https://doi.org/10.1007/s12565-021-00624-9

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