The ketogenic diet raises brain oxygen levels, attenuates postictal hypoxia, and protects against learning impairments

• Main Authors: Renaud C. Gom, Dhyey Bhatt, Bianca R. Villa, Antis G. George, Alexander W. Lohman, Richelle Mychasiuk, Jong M. Rho, G. Campbell Teskey
• Format: Article
• Language: English
• Published: Elsevier 2021-07-01
• Series: Neurobiology of Disease
• Subjects: Seizure; Oxygen; Ketones; Blood flow; Learning; β-Hydroxybutyrate
• Online Access: http://www.sciencedirect.com/science/article/pii/S096999612100084X

Objectives: A prolonged vasoconstriction/hypoperfusion/hypoxic event follows self-terminating focal seizures. The ketogenic diet (KD) has demonstrated efficacy as a metabolic treatment for intractable epilepsy and other disorders but its effect on local brain oxygen levels is completely unknown. This study investigated the effects of the KD on tissue oxygenation in the hippocampus before and after electrically elicited (kindled) seizures and whether it could protect against a seizure-induced learning impairment. We also examined the effects of the ketone β-hydroxybutyrate (BHB) as a potential underlying mechanism. Methods: Male and female rats were given access to one of three diet protocols 2 weeks prior to the initiation of seizures: KD, caloric restricted standard chow, and ad libitum standard chow. Dorsal hippocampal oxygen levels were measured prior to initiation of diets as well as before and after a 10-day kindling paradigm. Male rats were then tested on a novel object recognition task to assess postictal learning impairments. In a separate cohort, BHB was administered 30 min prior to seizure elicitation to determine whether it influenced oxygen dynamics. Results: The KD increased dorsal hippocampal oxygen levels, ameliorated postictal hypoxia, and prevented postictal learning impairments. Acute BHB administration did not alter oxygen levels before or after seizures. Interpretation: The ketogenic diet raised brain oxygen levels and attenuated severe postictal hypoxia likely through a mechanism independent of ketosis and shows promise as a non-pharmacological treatment to prevent the postictal state.