Ischemic preconditioning with a ketogenic diet improves brain ischemic tolerance through increased extracellular adenosine levels and hypoxia-inducible factors.

•The KD reduced infarct volume in mice with MCAO.•The KD increased rCBF and extracellular adenosine levels in ischemic region.•The KD protected against brain ischemic injury and increased Akt and ERK1/2 phosphorylation via A1 adenosine receptor activation.•The KD increased HIF-regulated genes expression after brain ischemia.•The KD upregulated HIF-1α/HIF-2α protein levels and EPO/VEGF protein contents.