Omotoso Gabriel Olaiya, Arietarhire Leviticus Oghenevurinrin, Ukwubile Ileje Inelo, Gbadamosi Ismail Temitayo
Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
Basic Clin Neurosci. 2020 Sep-Oct;11(5):609-618. doi: 10.32598/bcn.9.10.300. Epub 2020 Sep 1.
This study aimed at assessing the protective mechanisms of Kolaviron (KV) on the cerebellum in a rat model of demyelination.
Twenty-eight male Wistar rats were used in the present study. They were randomly divided into 4 groups of 7 rats. Group A (control) received corn oil (0.5 mL/kg/d); group B received 0.2% Cuprizone (CPZ); group C was treated with 200 mg/kg/d of KV, and group D received 0.2% CPZ and 200 mg/kg/d KV for 6 weeks. CPZ powder was mixed with the regular diet while KV was dissolved in corn oil and administered orally. A behavioral test was conducted at the termination of the experiment. Thereafter, the animals were sacrificed and their brains were removed with the excision of the cerebellum. A part of the cerebelli underwent tissue processing with a series of 5 μm thick sections cut from paraffin blocks for histological and immunohistochemical assessment. Besides, the remaining cerebellar tissues were homogenized for the spectrophotometric assays of Oxidative Stress (OS) parameters.
The current research findings revealed minimal weight gain following CPZ treatment, but significant weight increase in KV-treated rats. CPZ treatment was associated with a reduction in the number of the line crossed, rearing frequency, rearing duration, center square entry, and center square duration; however, it increased the freezing time, i.e. significantly reversed in the KV-treated animals. Oxidative markers, such as Superoxide Dismutase (SOD) and GPx were reduced in CPZ-treated rats with elevated MDA levels. However, these data were significantly reversed by the co-administration of CPZ and KV. At the tissue level, the cerebellar cortex was characterized by poorly defined layers, cryptic granules, as well as chromatolysis and pyknotic Purkinje cells with the evidence of hypertrophic astrogliosis.
CPZ treatment significantly depressed locomotor and exploratory activities. Furthermore, it increased OS and cerebellar toxicity. However, KV intervention significantly enhanced behavioral functions and ameliorated CPZ-induced cerebellar degeneration. Moreover, it considerably regulated OS markers in the cerebellum of the rat model of demyelinating diseases.
本研究旨在评估可乐维隆（KV）对脱髓鞘大鼠模型小脑的保护机制。
本研究使用了28只雄性Wistar大鼠。它们被随机分为4组，每组7只。A组（对照组）给予玉米油（0.5 mL/kg/d）；B组给予0.2%的铜螯合剂（CPZ）；C组用200 mg/kg/d的KV进行治疗，D组给予0.2%的CPZ和200 mg/kg/d的KV，持续6周。CPZ粉末与常规饮食混合，而KV溶解在玉米油中并口服给药。在实验结束时进行行为测试。此后，处死动物并取出大脑，切除小脑。一部分小脑进行组织处理，从石蜡块上切下一系列5μm厚的切片用于组织学和免疫组织化学评估。此外，将剩余的小脑组织匀浆用于氧化应激（OS）参数的分光光度测定。
当前的研究结果显示，CPZ治疗后体重增加极少，但KV治疗的大鼠体重显著增加。CPZ治疗导致穿越次数、竖毛频率、竖毛持续时间、进入中央方格次数和在中央方格停留时间减少；然而，它增加了僵住时间，即在KV治疗的动物中显著逆转。在CPZ治疗的大鼠中，超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）等氧化标志物减少，丙二醛（MDA）水平升高。然而，CPZ和KV联合给药可显著逆转这些数据。在组织水平上，小脑皮质的特征是层界不清、颗粒模糊，以及出现染色质溶解和固缩的浦肯野细胞，并伴有肥大性星形胶质细胞增生的证据。
CPZ治疗显著抑制运动和探索活动。此外，它增加了氧化应激和小脑毒性。然而，KV干预显著增强了行为功能，改善了CPZ诱导的小脑变性。此外，它还显著调节了脱髓鞘疾病大鼠模型小脑中的氧化应激标志物。
