Quercetin as a Promoter of Cns Repair: Investigating Cerebellar Remyelination in Cuprizone-Exposed Wistar Rats

Demyelination refers to the pathological loss or damage of the myelin sheath surrounding nerve fibers (axons) in the nervous system. Remyelination is the natural repair process by which damaged or lost myelin sheaths in the nervous system are regenerated and restored around axons. Cuprizone, a widely known copper chelator, has been employed to model demyelination in rats. Quercetin is a special subclass of flavonoid that is present in fruits and vegetables and usually present in average diets. The aim of this study is to explore the neurotoxic impacts of cuprizone on the cerebellum of Wistar rats, its effect on certain patterns of behaviour and quercetin effects in promoting cerebellar remyelination. Wistar rats were grouped into three categories; Group A which represents the control group received standard rat chow for five weeks and vehicle for a week orally via metal cannula; Group B was administered 0.2% cuprizone diet for five weeks for acute demyelination, and vehicle for a week post demyelination; Group C received 0.2% cuprizone diet for five weeks for acute demyelination and quercetin for a week (40mg/kg body weight). The animals were assessed for grip strength and limb coordination parameters. Cerebellum was excised from the whole brain and processed for biochemical assays, tissue histology, and immunohistochemistry. Inflammatory status was also assessed using interleukin-1β as a biomarker. Results revealed slow weight improvement, increased pro-inflammatory activities and motor function deficits in Group B, but no differential changes in the cytoarchitecture for Haematoxylin and Eosin stain across the groups, Cresyl fast violet stain also presented similar Nissl bodies’ density across the groups. Cell count analysis for immunostains revealed oligodendrocyte reduction, increased astrocyte migration and microglial activation during the cuprizone-induced demyelination phase. Quercetin supplementation resulted in oligodendrocyte repopulation, reduced astrocyte migration and reduced microgliosis (microglial activation).
Keywords: cuprizone(cpz), quercetin (que), demyelination, neuroinflammation, remyelination, cerebellum