Table 1

Animal and basic science studies on effects of ketone administration on 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

AcAc, acetoacetate; BHB, β-hydroxybutyrate; In vivo, in vivo experiment; i.v., intravenous; p.o., per orally; TBI, traumatic brain injury.

White and Venkatesh Critical Care 2011 15:219   doi:10.1186/cc10020