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

Demyelination is the loss or destruction of the protective myelin sheath surrounding nerve fibers, which disrupts the transmission of nerve impulses. Remyelination is the natural repair process by which new myelin sheaths are generated around axons in the central nervous system, restoring nerve function. Cuprizone, a generally known copper chelator, has been adopted to mimic demyelination in rats and it causes behavioural deficits. Quercetin is a naturally occurring flavonoid found in a variety of fruits and vegetables, such as onions, apples, and berries. It is known for its wide range of potential health benefits, including its antioxidant, anti-inflammatory, and neuroprotective properties. The aim of this study is to investigate the effects of cuprizone-induced demyelination on the hippocampus of Wistar rats and assessed the potential of quercetin to promote recovery. Wistar rats were grouped into three categories; Group A which represents the control group received standard rat feed for five weeks and vehicle solution (0.1% DMSO in Phosphate buffered saline) for a week orally via metal cannula; Group B was administered 0.2% cuprizone diet for five weeks for acute demyelination, and vvehicle (0.1% DMSO in PBS) 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). Behavioural analysis using the Morris water maze revealed spatial memory deficits in the cuprizone-treated animals. Biochemical assays confirmed that cuprizone increased pro-inflammatory markers (IL-1β, TNF-α). Histological analysis showed no significant changes in overall cell structure (H&E) or Nissl density (Cresyl fast violet). However, immunohistochemistry revealed that cuprizone induced oligodendrocyte apoptosis, astrogliosis, and microglial activation. Subsequent treatment with quercetin successfully promoted oligodendrocyte repopulation while reducing both astrocyte migration and microgliosis, highlighting its therapeutic potential in mitigating neuroinflammation and supporting remyelination.


Keywords: Cuprizone (CPZ), Quercetin (QUE), Demyelination, Neuroinflammation, Remyelination, Dentate Gyrus(Hippocampu