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Table 1 Animal and basic science studies on effects of ketone administration on brain injury

From: Clinical review: Ketones and brain injury

Mechanism of injury Reference Ketone source Study Outcome
Glutamate-induced injury Massieu and colleagues [55] i.v. AcAc infusion for 14 days in adult rodent model prior to and during glutamate-induced injury Decreased neuronal damage, decreased lesion volume and increased cellular ATP levels
  Noh and colleagues [57, 58] p.o. 21-day-old mice fed ketogenic diet prior to kianic-induced neuronal damage Preservation of neurons in hippocampus by inhibiting caspase-3-mediated apoptosis
  Mejia-Toiber and colleagues [56] In vivo BHB applied before glutamate-induced neurotoxicity BHB reduces injury and lipoperoxidation
  Maalouf and colleagues [54] In vivo Addition of BHB to in vitro model of glutamate neurotoxicity Reduction in free radical formation and enhanced mitochondrial respiration
Cerebral hypoxia Puchowicz and colleagues [60] p.o. Rats fed ketogenic diet 3 weeks prior to hypoxic injury Decreased cerebral lactate and increased tolerance of hypoxia
  Masuda and colleagues [59] In vivo Rat neurons exposed to hypoxia following treatment with BHB Decreased cell death and number of apoptotic cells with maintenance of mitochondrial membrane
Cerebral ischemia Suzuki and colleagues [70] i.v. Rats infused with BHB 3 to 6 hours after bilateral carotid artery occlusion Decreased cerebral edema and sodium content and increased ATP levels
  Suzuki and colleagues [63] i.v. BHB infusions following occlusion of the middle cerebral artery 50% reduction in cerebral infarct volume
  Marie and colleagues [69] Fasted Adult rats fasted for 24 hours before four-vessel occlusion Decreased mortality, post-traumatic seizures and brain lactate
  Go and colleagues [68] Fasted Starvation-induced ketosis followed by carotid occlusion Fasting protected rats from brain infarction
Traumatic brain injury Prins and colleagues [65] i.v. BHB infusion following TBI in adult rats Increase in serum BHB and cerebral BHB and improved cortical ATP levels
  Prins and colleagues [64] p.o. Rats with TBI fed ketogenic diet 50% reduction in cortical contusion volume
  Biros and Nordness [67] p.o. Rats of differing ages fed ketogenic diet following TBI Younger rats demonstrated larger reduction in contusion volume
  Hu and colleagues [61, 62] p.o. Rats fed ketogenic diet prior to TBI Reduced brain edema and cellular apoptosis in rats fed ketone diet
  1. AcAc, acetoacetate; BHB, β-hydroxybutyrate; In vivo, in vivo experiment; i.v., intravenous; p.o., per orally; TBI, traumatic brain injury.