Cerebral ischemia alters glucose transporter kinetics across rat brain microvascular endothelium. Quantitative analysis by an in situ brain perfusion method.
The purpose of this study was to quantify the changes of blood-brain barrier glucose transporter kinetics following cerebral ischemia using an in situ brain perfusion technique. Sixty-four adult male Sprague-Dawley rats were divided into control and ischemia groups, and a four-vessel occlusion model was used to provide an ischemic insult. To obtain regional capillary permeability area products of glucose and regional perfusion fluid flow rates, the perfusion fluid was dually labeled with 2-deoxy[14C]glucose and [3H]diazepam, and the brain was perfused at a constant rate via the external carotid artery. After sampling tissues from the brain, dual scintillation counting was performed and both regional perfusion fluid flow rates and regional capillary permeability area products were calculated. We determined kinetic parameters, including Vmax, Km and Kd as described in the Michaelis-Menten equation, by the non-linear least squares method. In the ischemia group, a decrease in Vmax and an increase in Km were recognized, which mean decreases in the affinity and the number of functioning glucose transporters. These results suggest that cerebral ischemia downregulates the blood-brain barrier glucose transporters.
Suzuki
H
H
Department of Neurosurgery, University of Kobe Medical School, Japan.
Nagashima
T
T
Fujita
K
K
Tamaki
N
N
Sugioka
K
K
Yamadori
T
T
Yamaguchi
M
M
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D005947:Glucose