Blood-brain barrier glutamine transport during normoglycemic and hyperglycemic focal cerebral ischemia.
This study examines the effects of middle cerebral artery (MCA) occlusion in the rat on blood to brain glutamine transport, a potential marker of early endothelial cell dysfunction. It also examines whether the effects of ischemia on glutamine transport are exacerbated by hyperglycemia. In pentobarbital-anesthetized rats, 4 hours of MCA occlusion resulted in a marked decline in the influx rate constant for [14C]L-glutamine from 16.1+/-1.2 microL.g(-1).min(-1) in the contralateral hemisphere to 7.3+/-2.5 microL.g(-1).min(-1) in the ischemic core (P < 0.001). This reduction was even greater in xylazine-ketamine-anesthetized rats in which the influx decreased to 2.6+/-1.1 microL.g(-1) min(-1). This greater reduction appears related to the hyperglycemia induced by xylazine-ketamine anesthesia. Glucose injection in pentobarbital-anesthetized rats also resulted in a greater decline in [14C]L-glutamine influx in the ischemic core but had no effect on the contralateral tissue. The effects of hyperglycemia on glutamine transport in the ischemic tissue were associated with a decline in plasma volume, which may reflect either endothelial cell swelling or plugging of the microvasculature. The reduction in glutamine transport during ischemia was progressive, but even as early as 1 hour, there was a 60% and 40% decline in influx in hyperglycemic and normoglycemic rats, respectively. The fall in [14C]L-glutamine influx may reflect a dissipation of the endothelial cell [Na+] gradient. A decline in this gradient would affect many blood-brain barrier transporters with potentially deleterious effects on the ischemic brain.
Kawai
N
N
Department of Surgery, University of Michigan, Ann Arbor 48109-0532, USA.
Stummer
W
W
Ennis
S R
SR
Betz
A L
AL
Keep
R F
RF
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D005973:Glutamine / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D005973:Glutamine