β-hydroxybutyrate attenuates demyelination, modulates microglial phenotype and supports blood-brain barrier integrity in a cuprizone-induced mouse model of demyelination

Zhang, Ning; Lin, Li; Li, Sen; Khan, Muhammad Akram; Tahir, Adnan Hassan; Rahim, Muhammad Farhan; Wang, Ting; Zhao, Jing; Zhang, Ruiyan

doi:10.1016/j.jff.2023.105580

Cited by 1 publication

(2 citation statements)

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“…The neuroprotective properties of the KD have been highlighted in various experimental models. For example, KD could improve the synaptic deficits reported in AD and depression [46,47] and restored motor deficits in the EAE model of MS mice. [48,49] Additionally, excessive inflammatory reaction and immune response were significantly attenuated by KD treatment.…”

Section: Discussionmentioning

confidence: 99%

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A High MCT‐Based Ketogenic Diet Suppresses Th1 and Th17 Responses to Ameliorate Experimental Autoimmune Encephalomyelitis in Mice by Inhibiting GSDMD and JAK2‐STAT3/4 Pathways

Zhang,

Sun,

Wang

et al. 2023

Molecular Nutrition Food Res

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ScopeInflammation and pyroptosis play important roles in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In this study, we evaluated the therapeutic potential of ketogenic diet (KD) in EAE.Methods and resultsThe administration of KD reduces demyelination and microglial activation in the spinal cord of EAE mice. Meanwhile, KD decreases the levels of Th1 and Th17 associated cytokines/transcription factors production (T‐bet, IFN‐γ, RORγt, and IL‐17) and increases those of Th2 and Treg cytokines/transcription factors (GATA3, IL‐4, Foxp3, and IL‐10) in the spinal cord and spleen. Corresponding, KD reduces the expression of chemokines in EAE, which those chemokines associate with T‐cell infiltration into central nervous system (CNS). In addition, KD inhibits the GSDMD activation in microglia, oligodendrocyte, CD31+ cells, CCR2+ cells, and T cells in the spinal cord. Moreover, KD significantly decreases the ratios of p‐JAK2/JAK2, p‐STAT3/STAT3, and p‐STAT4/STAT4, as well as GSDMD in EAE mice.Conclusionsthis study demonstrates that KD reduces the activation and differentiation of T cells in the spinal cord and spleen and prevents T cell infiltration into CNS of EAE via modulating the GSDMD and STAT3/4 pathways, suggesting that KD is a potentially effective strategy in the treatment of MS.

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Section: Discussionmentioning

confidence: 99%

“…CCR2 was a marker for peripheral macrophages/monocytes invading the CNS. [47,58] Both peripheral and CNS macrophages and CNS microglia contribute to the EAE. [25] However, neither macrophage nor microglia cell death has been extensively studied in MS, whereas iron-containing plaques in microglial degeneration have been observed.…”

Section: Discussionmentioning

confidence: 99%