The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy volunteers.
The effects of glucose deprivation on cerebral blood flow (CBF) have been extensively investigated during insulin-induced hypoglycemia in laboratory animals. Pharmacological doses of glucose analog, 2-deoxyglucose (2DG), is an alternative glucoprivic agent that in contrast to insulin, directly inhibits glycolysis and glucose utilization. Both glucoprivic conditions markedly increase CBF in laboratory animals. How 2DG affects CBF in humans is still undetermined. In the present study we have employed H215O positron emission tomography (PET) to examine the effects of pharmacological doses of 2DG (40 mg/kg) on regional and global cerebral blood flow in 10 brain areas in 13 healthy volunteers. 2DG administration significantly raised regional CBF (rCBF) in the cingulate gyrus, sensorimotor cortex, superior temporal cortex, occipital cortex, basal ganglia, limbic system and hypothalamus. 2DG produced a trend towards elevated CBF in whole brain and frontal cortex, while no changes were observed in the corpus callosum and thalamus. In addition, 2DG significantly decreased body temperature and mean arterial pressure (MAP). Maximal percent changes in hypothalamic rCBF were significantly correlated with maximal changes in body temperature but not with MAP. These results indicate that cerebral glucoprivation produced by pharmacological doses of 2DG is accompanied by widespread activation of cortical and subcortical blood flow and that the blood flow changes in the hypothalamus may be related to 2DG-induced hypothermia.
Elman
I
I
Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. elman.igor@mgh.harvard.edu
Sokoloff
L
L
Adler
C M
CM
Weisenfeld
N
N
Breier
A
A
D000328:Adult; D001519:Behavior / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003847:Deoxyglucose / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D013223:Statistics as Topic; D014055:Tomography, Emission-Computed
D003847:Deoxyglucose