Abstract
Objective: The study aimed to assess the possible role of quercetin, pioglitazone, metformin, and dapagliflozin in the enhancement of remyelination process after ethidium bromide (EB)-induced demyelination.
 Methods: The study was conducted on 60 male Wister rats (250–300 g), randomly divided into sham-operated group and five demyelination groups (each of 10 rats) which subjected to intrapontine stereotaxic injection of EB (10 μl of 0.1% EB) to induce demyelination. Then, randomly subdivided into: EB control group: Rats were treated with normal saline, quercetin-treated group (50 mg/kg/day), pioglitazone-treated group (10 mg/kg/day), metformin-treated group (500 mg/kg/day), and dapagliflozin-treated group (10 mg/kg/day). Behavioral tests (beam balance, foot fault, rotarod, and inverted screen) were conducted for all groups as well as biochemical analysis of LINGO-1 and myelin basic protein (MBP) mRNAs and histological examination of pontine tissues.
 Results: The EB control group showed deterioration of motor performance on behavioral tests. Degenerative changes were observed in pontine tissue on histological examination together with upregulation of LINGO-1 protein and downregulation of MBP level. While the treated groups after EB demyelination showed significant improvement in motor performance and decreased degenerated neurons in histological examination with upregulation of MBP level and downregulation of LINGO-1 protein level.
 Conclusion: Quercetin, metformin, dapagliflozin, and pioglitazone showed neuroprotective effect and enhancement of remyelination process.
Highlights
Multiple sclerosis is a debilitating disease of the central nervous system (CNS), typically presents in the third or fourth decade of life
The adult CNS has a limited capacity to repair damaged tissue, and this restriction is related to neurons plus their axons and mature oligodendrocytes that are unable to compensate for myelin loss as they degenerate [2]
Quercetin, metformin, dapagliflozin, and pioglitazone treatment showed significant downregulation in the level of LINGO-1 mRNA expression when compared to the ethidium bromide (EB) control group on the 21st day (Fig. 5a)
Summary
Multiple sclerosis is a debilitating disease of the central nervous system (CNS), typically presents in the third or fourth decade of life. The adult CNS has a limited capacity to repair damaged tissue, and this restriction is related to neurons plus their axons and mature oligodendrocytes that are unable to compensate for myelin loss as they degenerate [2]. This demyelination process usually triggers a spontaneous myelin repair process, known as remyelination [3]. Each phase of remyelination is regulated by a complex pattern of signaling events, the dysregulation of which will result in remyelination impairment [5]
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