Comparison of Exogenous Ketone Supplements on Latency to CNS Oxygen Toxicity Seizures in Middle‐Aged Rats

Abstract

Central nervous system oxygen toxicity (CNSOT) seizures manifest as tonic‐clonic seizures and are a limitation of hyperbaric oxygen therapy (HBOT) and Navy SEAL divers breathing 100% oxygen using closed circuit rebreathers. Previous studies showed that ketone ester (1,3‐butanediol acetoacetate diester, KE) delayed latency to seizures in 3 months old Sprague‐Dawley rats. Our present study explores the effect of exogenous ketone supplements on CNSOT seizures across different ketone formulations and dosages in 18‐month‐old Sprague‐Dawley rats that resemble middle age in humans. Rats received one dose of the ketogenic agent by oral gavage 60 minutes before a dive. Treatment groups included control (water), 1,3‐butanediol acetoacetate diester (KE 10g/kg, KE/2 5g/kg), KE+MCT (KE 5g/kg + medium chain triglyceride 5g/kg) and KS+MCT (CaNaBHB 5g/kg + MCT 5g/kg). To simulate a dive, rats were placed on 100% oxygen followed by gas compression to 5 atmospheres absolute (ATA) in a hyperbaric chamber and remained at 5 ATA until exhibiting CNSOT seizures, defined by tonic‐clonic movements. Upon seizure presentation, experiments were immediately terminated and the chamber was decompressed at a rate of 1 ATA/min. A small sample of blood was drawn and tested immediately for glucose and R‐beta‐hydroxybutyrate (βHB) levels. While βHB levels were significantly elevated in all aged‐rat treatment groups, compared to control, the latency to seizures was significantly delayed only in KE (p=0.0003), KE/2 (p=0.023) and KE+MCT (p=0.028) groups. In these groups, the severity of seizures was less than control. The latency to seizures in 18 months old rats were delayed by 179% in KE, 219% in KE+MCT and 55% in KE/2 groups, while only by 29% in KS+MCT group. Previous studies indicate that 3‐month‐old Sprague‐Dawley rats presented 574 ± 116% latency to seizure compared to control indicating age related influence on latency to seizure. Glucose levels were not significantly different from the control group. We can conclude that middle‐aged rats demonstrated increased latency to CNSOT seizures, although at a different rate than younger rats, in response to ketogenic supplements and their combinations, while elevating βHB levels.Support or Funding InformationThis work was supported by ONR Grant N000141310062 (DPD), ONR, Undersea Medicine Program (N000140710890, JBD), ONR, Undersea Medicine Program (N000141612537, JBD).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.