Ketone bodies promote stroke recovery via GAT-1-dependent cortical network remodeling

• DOI: 10.1016/j.celrep.2023.112294
• Publication Date: 2023-03-21T20:25:47Z
• Authors: Yu-Hui Lin; Di Yang; Huan-Yu Ni; Xiu-Mei Xu; Feng Wu; Long Lin; Jie Chen; Yan-Yu Sun; Zhen-Quan Huang; Shi-Yi Li; Pei-Lin Jiang; Hai-Yin Wu; Lei Chang; Bo Hu; Chun-Xia Luo; Jin Wu; Dong-Ya Zhu
• Keywords: Stroke; Stroke Recovery

Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role network excitability during repair phase for stroke recovery. Here, we show that β-hydroxybutyrate (β-HB), an essential ketone body (KB) component, positively correlated with improved outcomes in patients promotes rodents phase. These beneficial effects β-HB depend on HDAC2/HDAC3-GABA transporter 1 (GAT-1) signaling-mediated enhancement phasic GABA inhibition peri-infarct cortex structural plasticity ipsilateral cortex, contralateral corticospinal tract. Together available clinical approaches elevate KB levels, our results offer clinically translatable means Furthermore, GAT-1 can serve as pharmacological target developing