The effects of pharmacologic doses of 2-deoxy-D-glucose on local cerebral blood flow in the awake, unrestrained rat.
Previous studies on the effects of acute insulin-induced hypoglycemia on cerebral blood flow (CBF) have resulted in conflicting results. An alternate approach to the study of glucoprivation is the administration of pharmacologic doses of the glucose analogue, 2-deoxy-D-glucose (2-DG). 2-DG is transported across the blood-brain barrier into brain tissue where it is phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG-6-P) but not metabolized further. The 2-DG-6-P accumulates and inhibits the conversion of glucose-6-phosphate to fructose-6-phosphate, thus blocking glycolysis and glucose metabolism. In the present study we have employed the [14C]iodoantipyrine method to examine the effects of a pharmacologic dose (500 mg/kg) of 2-DG on local cerebral blood flow (lCBF) in 29 regions of the brain in conscious, unrestrained, adult male rats. The 2-DG treatment raised arterial plasma glucose levels from 8 to 17 mM without affecting arterial blood pO2, pCO2, or pH but increased lCBF in most brain regions examined. The largest increases were in the cerebral cortex, basal ganglia, and thalamic nuclei (+65 to +157%). Smaller increases were found in most structures of the limbic system, brainstem, and white matter, and no changes in lCBF were seen in the cerebellar cortex and ventral medial hypothalamus. The results indicate that cerebral glucoprivation produced by pharmacological doses of 2-deoxyglucose is accompanied by substantial increase in blood flow in most regions of the brain.
Department of Psychiatry, University of Maryland School of Medicine, Baltimore 21228.
A
A
Breier
A M
AM
Crane
C
C
Kennedy
L
L
Sokoloff
D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003847:Deoxyglucose / Q000494:pharmacology*; D006400:Hematocrit; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D003847:Deoxyglucose