title: Protective effects of d-3-hydroxybutyrate and propionate during hypoglycemic coma: clinical and biochemical insights from infant rats.
abstract: BACKGROUND
  d-3-hydroxybutyrate (3OHB) is an alternative energy substrate for the brain during hypoglycemia, especially during infancy. Supplementation of 3OHB during sustained hypoglycemia in rat pups delays onset of burst suppression coma, but is associated with white matter injury and increased mortality. The biochemical basis for this ambivalent effect is not known. It may be related to an anaplerotic or gluconeogenetic deficit of 3OHB.
  
  
  RESULTS
  We studied clinical alertness, EEG and brain metabolites (acyl-carnitines, amino acids, glycolytic and pentose phosphate intermediates) in 13 day-old rat pups during insulin induced hypoglycemic coma and after treatment with 3OHB alone or in combination with the anaplerotic substrate propionate. Clinically, treatment with 3OHB and propionate resulted in an alert state and EEG improvement, while treatment with 3OHB alone resulted in an improved EEG but animals remained clinically comatose. Biochemically, both treatments resulted in correction of cerebral glutamate and ammonia levels but not of gluconeogenetic substrates and pentose phosphate metabolites.
  
  
  CONCLUSIONS
  3OHB treatment restores glutamate metabolism but cannot restore a glycolytic or pentose phosphate pathway deficit. Additional treatment with propionate significantly improved the clinical protective effect of 3OHB in hypoglycemic coma.
authors: Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital, 4480 Oak Street, Vancouver, BC, Canada V6H 3V4.schutz@interchange.ubc.ca
authors: Peter W
authors: PW
authors: Schutz
authors: Eduard A
authors: EA
authors: Struys
authors: Graham
authors: G
authors: Sinclair
authors: Sylvia
authors: S
authors: Stockler
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002624:Chemistry, Clinical; D005260:Female; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D007331:Insulin Coma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D011422:Propionates / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011422:Propionates; D020155:3-Hydroxybutyric Acid