The Protective Effect of Kolaviron on Molecular, Cellular, and Behavioral Characterization of Cerebellum in the Rat Model of Demyelinating Diseases

Abstract

Purpose of Study: This study was aimed at assessing the protective mechanisms of Kolaviron on the cerebellum in a rat model of demyelination. Methods: Twenty-eight male Wistar rats were used for the study. They were randomly divided into 4 groups and each group had 7 rats. Group A (control) received corn oil (0.5 ml/kg/day), Group B received 0.2% cuprizone (cpz), Group C was treated with 200 mg/kg/day of Kolaviron (kv), while Group D received 0.2% cuprizone (cpz) and 200 mg/kg/day Kolaviron (kv), for 6 weeks. Cuprizone powder was mixed with the regular diet while kv was dissolved in corn oil and administered orally. Behavioral test was conducted at the termination of the experiment. Thereafter, the animals were sacrificed and their brains were removed with excision of the cerebellum. Part of the cerebelli underwent tissue processing with a series of 5 µm thick sections cut from paraffin blocks for histological and immunohistochemical assessment, while the remaining cerebellar tissues were homogenized for spectrophotometric assays of oxidative stress parameters. Results: Findings revealed minimal weight gain following CPZ treatment, but significant weight increase in kolaviron-treated rats. CPZ treatment was associated with reduction in number of line crossed, rearing frequency, rearing duration, center square entry and center square duration, but increase in freezing time, which were reversed significantly in kolaviron-treated animals. Oxidative markers such as SOD and GPx were reduced in CPZ-treated rats with elevated MDA level. However, these were reversed significantly by co-administration of CPZ with kolaviron. At the tissue level, the cerebellar cortex was characterized by poorly defined layers, cryptic granules, chromatolytic and pyknotic Purkinje cells with evidence of hypertrophic astrogliosis. 4 Conclusion: CPZ treatment significantly depresses locomotor and exploratory activities as well as increases oxidative stress and cerebellar toxicity; however, kolaviron intervention significantly enhances behavioral functions, ameliorates CPZ-induced cerebellar degeneration and considerably regulates oxidative stress markers in the cerebellum of rat model of demyelinating diseases.