title: Blood-brain barrier transport of an essential amino acid after cerebral ischemia reperfusion injury.
abstract: Under pathophysiological conditions such as -cerebral ischemia-reperfusion (IR), damage to cerebrovascular endothelial cells causes alterations in the blood-brain barrier (BBB) function that can exacerbate neuronal cell injury and death. Clarifying changes in BBB transport in the early period of IR is important for understanding BBB function during therapy after cerebral ischemia. The present study was aimed at clarifying changes during IR in the BBB transport of L-phenylalanine (Phe) as a substrate of L-type amino acid transporter 1. An IR model was produced in mice by blood recirculation following occlusion of the middle cerebral artery. Permeability of the BBB to [(3)H]Phe was measured after IR injury using the brain perfusion method. Confocal microscopy of the IR injury showed no brain penetration of fluorescent tracer, thus confirming BBB integrity during 45 min of ischemia. Tight junction opening was not observed at 30 min after reperfusion following ischemia for 45 min. At the time of IR, [(3)H]Phe uptake into the brain appeared saturated. The Michaelis constant and maximum transport velocity in the IR group was reduced by 22 % compared with those in controls. These results suggest that the intrinsic transport clearance of Phe is slightly decreased in the early phase of IR.
authors.affiliation: Department of Applied Pharmacy, Nihon University School of Pharmacy, Chiba, Japan. suzuki.toyofumi@nihon-u.ac.jp
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Aya
authors.initials: A
authors.lastname: Ohmuro
authors.forename: Masaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takayuki
authors.initials: T
authors.lastname: Furuishi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tomono
mesh_terms: D000601:Amino Acids, Essential / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D004195:Disease Models, Animal; D005070:Evans Blue; D019793:Fluorescein; D008297:Male; D051379:Mice; D015427:Reperfusion Injury / Q000473:pathology*; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
chemical_list: D000601:Amino Acids, Essential; D014316:Tritium; D005070:Evans Blue; D019793:Fluorescein