| First Author | Lin C | Year | 2023 |
| Journal | Eur J Pharmacol | Volume | 955 |
| Pages | 175933 | PubMed ID | 37481199 |
| Mgi Jnum | J:348834 | Mgi Id | MGI:7644010 |
| Doi | 10.1016/j.ejphar.2023.175933 | Citation | Lin C, et al. (2023) Ketogenic diet and beta-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway. Eur J Pharmacol 955:175933 |
| abstractText | 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 beta-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-kappaB. 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. |
