Regional alterations in an excitatory amino-acid transporter, blood flow, and glucose metabolism after middle cerebral artery occlusion in the rat.
A rise in the extracellular concentration of excitatory amino acids (EAA) plays a pivotal role in ischemic brain injury. EAA concentrations are regulated by uptake mechanisms through high-affinity EAA transporters. Since EAA uptake is energy-dependent, it is a matter of interest to explore the relationship between the EAA transporter and derangement of flow-metabolism during ischemia. We examined the regional changes in EAA transporters after permanent occlusion of the middle cerebral artery in rats by in vitro autoradiography using [3H]-D-aspartate as a ligand, and correlated these changes to the local cerebral blood flow (LCBF) and local cerebral glucose metabolism (LCMRglc) determined by in vivo double-labeled autoradiography. The values of specific binding of [3H]-D-aspartate decreased maximally by 20% in the ischemic core. The magnitude of the reduction in specific binding correlated well with the changes in LCBF and LCMRglc. In half of the regions with LCMRglc between 80 and 120% of the intact side, the values of the specific binding were relatively preserved, while in the remainder of the regions in the ischemic hemisphere, with LCMRglc ranging from 40 to 160% of the intact side, there was a reduction in specific binding. These results suggest that energy failure and the related perturbation caused by ischemia can decrease EAA uptake capacity, leading to further deterioration.
Gomi
S
S
Department of Neurology, University of Pennsylvania, Philadelphia 19104-6063, USA.
Karp
A
A
Greenberg
J H
JH
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001345:Autoradiography; D001794:Blood Pressure; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism; D020367:Iofetamine / Q000493:pharmacokinetics; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012044:Regression Analysis; D014316:Tritium
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D019275:Radiopharmaceuticals; D014316:Tritium; D001224:Aspartic Acid; D003847:Deoxyglucose; D020367:Iofetamine; D005947:Glucose