Glycolytic inhibition by 2-deoxyglucose reduces hyperglycemia-associated mortality and morbidity in the ischemic rat.
Numerous laboratories have shown that hyperglycemia increases cerebral ischemic damage. This presumably results from increased lactate production and accumulation during ischemia. Although increased tissue lactic acidosis is associated with increased ischemic brain damage, this damage has not been directly linked to glycolytic flux. Because 2-deoxyglucose (2-DG) is a competitive inhibitor of glycolysis we tested its ability to reduce hyperglycemia-exacerbated ischemic brain damage. Severe forebrain ischemia was produced by the four-vessel occlusion model in rats. Four rats received 3 g/kg glucose and saline while a second group (n = 5) was injected with 3 g/kg glucose plus 1.6 g/kg 2-DG. A third group (n = 5) was treated with 1 g/kg glucose plus saline and a fourth group (n = 5) received 1 g/kg glucose and 1.6 g/kg 2-DG. All rats were injected i.p. 10 minutes prior to the ischemic insult with the same volume/kg body weight. All rats receiving the high dose of glucose alone (3 g/kg) were dead within 24 hours postischemia. Rats who received 2-DG in addition to 3 g/kg glucose showed only 40% mortality (p = 0.119 Fisher's Exact). 2-DG completely eliminated convulsions during the initial two hours of recovery which was significant (p = 0.008), however, all rats in both groups showed some convulsions by 24 hours postischemia. Among rats receiving the low glucose dose (1 g/kg), none of the rats receiving 2-DG died or convulsed by 24 hours postischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism; D003837:Deoxy Sugars / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D006885:Hydroxybutyrates / Q000097:blood; D006943:Hyperglycemia / Q000150:complications / Q000401:mortality*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D003837:Deoxy Sugars; D006885:Hydroxybutyrates; D003847:Deoxyglucose; D020155:3-Hydroxybutyric Acid