Dynamic Balance of Microglia and Astrocytes Involved in the Remyelinating Effect of Ginkgolide B

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disorder in the central nervous system (CNS), in which remyelination failure results in persistent neurologic impairment. Ginkgolide B (GB), a major terpene lactone and active component of Ginkgo biloba, has neuroprotective effects in several models of neurological diseases. Here, our results show, by using an in vivo cuprizone (CPZ)-induced demyelinating model, administration of GB improved behavior abnormalities, promoted myelin generation, and significantly regulated the dynamic balance of microglia and astrocytes by inhibiting the expression of TLR4, NF-κB and iNOS as well as IL-1β and TNF-α, and up-regulating the expression of Arg-1 and neurotrophic factors. GB treatment also induced the generation of oligodendrocyte precursor cells (OPCs). In vitro cell experiments yielded the results similar to those of the in vivo model. The dynamic balance by decreasing microglia-mediated neuroinflammation and promoting astrocyte-derived neurotrophic factors should contribute to endogenous remyelination. Despite GB treatment may represent a novel strategy for promoting myelin recovery, the precise mechanism of GB targeting microglia and astrocytes remains to be further explored.

Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis

“…While, at a late stage of remyelination, all these outcomes improved as in the control group, except for rotarod performance and iNOS and IGF-1 levels, which remained unchanged. These results are consistent with previous findings (Chami et al, 2017 ; Wang J. et al, 2020 ; Yin et al, 2020 ) and confirm our study design, in which we examined our results at different time points during remyelination to avoid the effect of spontaneous remyelination by CPZ withdrawal on therapeutic intervention and to see whether the drugs can alter clinical symptoms shortly after disease onset, simulating treatment in humans. Overall, our results successfully established the CPZ-induced demyelination model in mice, and it is an excellent model for generating many essential features of MS disease and could be used to perform remyelination tests in this study.…”

Cuprizone Affects Hypothermia-Induced Neuroprotection and Enhanced Neuroblast Differentiation in the Gerbil Hippocampus after Ischemia

“…In the present study, the CPZ group showed elevated IL-1β and TNF-α levels in the hippocampal homogenates, and several studies have demonstrated increases in TNF-α levels [57,58] and IL-1β levels in brain homogenates [39]. Inflammation induced by ischemia upregulates cytokines in the hippocampus, including in gerbils [34].…”

Encapsulation of bryostatin-1 by targeted exosomes enhances remyelination and neuroprotection effects in the cuprizone-induced demyelinating animal model of multiple sclerosis

“…22 iNOS and Arg1 are two classical markers of pro-inflammatory and neuroprotective microglia, respectively. 23 We used immunofluorescence to examine the expression of iNOS and Arg1 on Iba1-positive microglia. The results show that the expression of iNOS in microglia of ExoPs-treated mice was higher than that in ExoPs + Bryo-treated mice, but not significantly different from that in the ExoPs and Bryo alone treatment groups (Fig.…”