title: Blood-brain barrier glutamine transport during normoglycemic and hyperglycemic focal cerebral ischemia.
abstract: 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.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor 48109-0532, USA.
authors.forename: N
authors.initials: N
authors.lastname: Kawai
authors.forename: W
authors.initials: W
authors.lastname: Stummer
authors.forename: S R
authors.initials: SR
authors.lastname: Ennis
authors.forename: A L
authors.initials: AL
authors.lastname: Betz
authors.forename: R F
authors.initials: RF
authors.lastname: Keep
mesh_terms: 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
chemical_list: D005973:Glutamine