Cerebral ischemia affects glucose transporter kinetics across rat brain microvascular endothelium: quantitative analysis by an in situ brain perfusion method.
BACKGROUND
It has been reported that cerebral ischemia induces a dissociation between cerebral blood flow and blood-brain barrier glucose transport, but mechanisms of the dissociation are not yet clearly understood. Recent immunohistochemical studies reveal discrepancies of the results between physiologic and immunochemical studies. The purpose of this study was to quantify changes of the blood-brain barrier glucose transporter kinetics following cerebral ischemia by an in situ brain perfusion technique.


METHODS
Fifty-six adult male Sprague-Dawley rats were divided into control and ischemia groups, and four-vessel occlusion was done as an ischemic insult. To obtain regional capillary permeability surface area products of glucose and regional perfusion fluid flow rates, the perfusion fluid (HCO3-buffered saline) was dually labeled with [14C]-2-Deoxyglucose and [3H]-Diazepam, and the brain was perfused at a constant rate via the external carotid artery. After sampling tissues from three regions (frontal, frontoparietal lobe, and caudoputamen), dual scintillation counting was performed. From the results, we determined kinetic parameters, including Vmax, Km, and Kd as described in the Michaelis-Menten equation, by weighted nonlinear least squares method.


RESULTS
In the ischemia group, the affinity (1/Km) and the maximum glucose transport rate (Vmax) decreased significantly.


CONCLUSIONS
The results suggest that severe cerebral ischemia down-regulates the blood-brain barrier glucose transporter kinetics, and the discrepancies between physiologic and immunohistochemical studies may be derived from redistribution of transporters, some deformation of transporters, production of some inhibitors, recruitment of capillaries with different types of transporters, and/or the effect of surrounding glial reaction.
Suzuki
H
H
Department of Neurosurgery, University of Kobe Medical School, Japan.
Nagashima
T
T
Tamaki
N
N
Yamadori
T
T
D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002196:Capillaries; D002199:Capillary Permeability; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010477:Perfusion / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009004:Monosaccharide Transport Proteins