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Ketogenic diet and β-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway

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机构： [1]Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China [2]Department of Critical Care Medicine, Baiyun Branch, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510420, China [3]Department of Clinical Research Center, Hainan Provincial Hospital of Chinese Medicine, Haikou, Hainan, 570203, China

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关键词： Ketogenic diet β-Hydroxybutyrate IRAKM Ischemic brain injury Proinflammatory cytokines

摘要：

Ketogenic diet (KD) is a classical nonpharmacological therapy that has recently been shown to benefit cerebral ischemia, but the mechanism remains unclear. This study investigated the neuroprotective effects of KD pretreatment and β-hydroxybutyrate (BHB, bioactive product of KD) post-treatment in a mouse model of temporary middle cerebral artery occlusion (tMCAO). Neurological function, infarct volume, as well as inflammatory reactions are evaluated 24 h after ischemia. Results showed that both KD pretreatment or BHB post-treatment improved the Bederson score and Grip test score, reduced infarct volume and the extravasation of IgG, suppressed the over-activation of microglia, and modulated the expression of cytokines. Mechanically, we found that both KD pretreatment or BHB post-treatment significantly stimulated the expression of interleukin-1 receptor-associated kinase M (IRAKM) and then inhibited the nuclear translocation of NF-κB. IRAKM deletion (Irakm-/-) exacerbated tMCAO-induced neurovascular injuries, and aggravated neuroinflammatory response. Moreover, KD pretreatment or BHB post-treatment lost their neuroprotection in the tMCAO-treated Irakm-/- mice. Our results support that KD pretreatment and BHB post-treatment alleviate ischemic brain injury in mice, possibly via an IRAKM-dependent way.Copyright © 2023. Published by Elsevier B.V.

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出版当年[2022]版：

大类 | 2 区

医学

小类 | 2 区药学

最新[2025]版：

大类 | 3 区医学

小类 | 2 区药学

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第一作者机构： [1]Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China

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通讯机构： [1]Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China [*1]Department of Neurology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, Guangzhou, 510515, China.

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