Ischemic brain damage is not ameliorated by 1,3-butanediol in hyperglycemic rats.
OBJECTIVE
Treatment with the ketone body precursor 1,3-butanediol has been suggested to ameliorate hypoxic/ischemic brain damage. Butanediol could provide an alternative energy substrate for the brain, thereby decreasing the amount of glycolytically produced lactate. Hyperglycemia aggravates brain damage after brain ischemia and causes fatal postischemic seizures, probably by increasing the production of lactate and decreasing the pH. We studied whether butanediol treatment altered the adverse consequences following ischemia complicated by hyperglycemia.


METHODS
Hyperglycemic adult male rats were given 25 or 50 mmol.kg-1 body wt butanediol intravenously 30 minutes before 10 minutes of transient forebrain ischemia. Morphological evaluation was performed following perfusion-fixation after 15 hours of recovery. Blood concentrations of beta-hydroxybutyrate, acetoacetate, glucose, and lactate and brain tissue concentrations of energy metabolites were measured before and after ischemia.


RESULTS
Blood levels of ketone bodies increased in the butanediol-treated rats. Ischemia decreased the blood levels of acetoacetate but increased the levels of beta-hydroxybutyrate by a similar amount, resulting in unchanged high levels of total ketone bodies in the animals that received butanediol. Brain tissue levels of glucose, energy metabolites, and lactate showed no difference between butanediol- and saline-treated rats. Furthermore, compared with saline-treated animals butanediol-treated rats showed no decrease in brain damage and no attenuation in the development of postischemic seizures.


CONCLUSIONS
The ketone body precursor 1,3-butanediol offers no protective effect in transient forebrain ischemia complicated by hyperglycemia.
Lundgren
J
J
Department of Neurobiology, University of Lund, Sweden.
Smith
M L
ML
Mans
A M
AM
Siesjö
B K
BK
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001925:Brain Damage, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002072:Butylene Glycols / Q000627:therapeutic use*; D004569:Electroencephalography; D006943:Hyperglycemia / Q000150:complications*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000209:etiology
D002072:Butylene Glycols; D007657:Ketone Bodies; C028491:1,3-butylene glycol