The prevalence of neonatal hypoxic-ischemic encephalopathy (HIE), a devastating neurological injury, is increasing; thus, effective treatments and preventions are urgently needed. The underlying pathology of HIE remains unclear; recent research has focused on elucidating key features of the disease. A variety of diseases can be alleviated by consuming a ketogenic diet (KD) despite differences in pathogenesis and features, given the common mechanisms of KD-induced effects. Dietary modification is the most translatable, cost-efficient, and safest approach to treat acute or chronic neurological disorders and reduces reliance on pharmaceutical treatments. Evidence suggests that the KD can exert beneficial effects in animal models and in humans with brain injuries. The efficacy of the KD in preventing neuronal damage, motor alterations, and cognitive decline varies. Moreover, the KD may provide an alternative source of energy, enhance mitochondrial function, and reduce the expression of inflammatory and apoptotic mediators. Thus, this diet has attracted interest as a potential therapy for HIE. This review examined the role of the KD in HIE treatment and described the mechanisms by which ketone bodies (KBs) exert effects under pathological conditions and protect against brain damage; the evidence supports the implementation of dietary interventions as a therapeutic strategy for HIE. Future research should aim to elucidate the underlying mechanisms of the KD in patients with HIE and determine whether the effect of the KD on clinical outcomes can be reproduced in humans.
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Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USACtr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA
Schendel, Diana
Nelson, Karin B.
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Childrens Natl Med Ctr, Washington, DC 20010 USA
NINDS, Bethesda, MD 20892 USACtr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA
Nelson, Karin B.
Blair, Eve
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Univ Western Australia, Telethon Inst Child Hlth, Perth, WA 6009, AustraliaCtr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA
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Univ Int Florida, Escuela Med Herbert Wertheim, Dept Pediat, Dept Neurol,Nicklaus Childrens Hosp, Miami, FL USAUniv Int Florida, Escuela Med Herbert Wertheim, Dept Pediat, Dept Neurol,Nicklaus Childrens Hosp, Miami, FL USA
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State Washington Univ, Barnes Jewish & St louis childrens Hosp, St louis Med Ctr, Lauren V Ackerman Lab Surg Pathol, St Louis, MO USA
Washington Univ, Barnes Jewish & St Louis Childrens Hosp, Lauren V Ackerman Lab Surg Pathol, St Louis Ctr Med, St Louis, MO 63110 USAState Washington Univ, Barnes Jewish & St louis childrens Hosp, St louis Med Ctr, Lauren V Ackerman Lab Surg Pathol, St Louis, MO USA
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Childrens Hosp Michigan, Dept Pediat, Detroit, MI USAChildrens Hosp Michigan, Dept Pediat, Detroit, MI USA
Martinovski, Helen
Khanal, Luna
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Childrens Hosp Michigan, Dept Pediat, Detroit, MI USAChildrens Hosp Michigan, Dept Pediat, Detroit, MI USA
Khanal, Luna
Kraft, Debra
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Childrens Hosp Michigan, Dept Pediat, Detroit, MI USAChildrens Hosp Michigan, Dept Pediat, Detroit, MI USA
Kraft, Debra
Natarajan, Girija
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Childrens Hosp Michigan, Dept Pediat, Detroit, MI USA
Cent Michigan Univ, Dept Pediat, Mt Pleasant, MI USAChildrens Hosp Michigan, Dept Pediat, Detroit, MI USA
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Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ctr Ciencias Saude, Inst Ciencias Biomed, BR-21949900 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ctr Ciencias Saude, Inst Ciencias Biomed, BR-21949900 Rio De Janeiro, Brazil
Pimentel-Coelho, Pedro M.
Mendez-Otero, Rosalia
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Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ctr Ciencias Saude, Inst Ciencias Biomed, BR-21949900 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ctr Ciencias Saude, Inst Ciencias Biomed, BR-21949900 Rio De Janeiro, Brazil
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Univ Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Physiol, Auckland 92019, New ZealandUniv Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Physiol, Auckland 92019, New Zealand
Davidson, Joanne O.
Dhillon, Simerdeep K.
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Univ Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Physiol, Auckland 92019, New ZealandUniv Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Physiol, Auckland 92019, New Zealand
Dhillon, Simerdeep K.
Zhou, Kelly
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Univ Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Physiol, Auckland 92019, New ZealandUniv Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Physiol, Auckland 92019, New Zealand
Zhou, Kelly
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Bennet, Laura
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Thoresen, Marianne
Gunn, Alistair J.
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Univ Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Physiol, Auckland 92019, New ZealandUniv Auckland, Fac Med & Hlth Sci, Sch Med Sci, Dept Physiol, Auckland 92019, New Zealand
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Univ Barcelona, Hosp St Joan de Deu, Serv Neonatol, E-08007 Barcelona, SpainUniv Barcelona, Hosp St Joan de Deu, Serv Neonatol, E-08007 Barcelona, Spain
Garcia-Alix, A.
Arnaez, J.
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Hosp Univ Burgos, Serv Neonatol, Burgos, SpainUniv Barcelona, Hosp St Joan de Deu, Serv Neonatol, E-08007 Barcelona, Spain