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 [3H]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, [3H]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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abbott NJ, Romero IA (1996) Transporting therapeutics across the blood-brain barrier. Mol Med Today 2:106–113
Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM (1999) Selective expression of the large neutral amino acid transporter at the blood-brain barrier. Proc Natl Acad Sci USA 96:12079–12084
Brown RC, Davis TP (2002) Calcium modulation of adherens and tight junction function: a potential mechanism for blood-brain barrier disruption after stroke. Stroke 33:1706–1711
Candelario-Jalil E (2009) Injury and repair mechanisms in ischemic stroke: considerations for the development of novel neurotherapeutics. Curr Opin Investig Drugs 10:644–654
del Amo EM, Urtti A, Yliperttula M (2008) Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2. Eur J Pharm Sci 35:161–174
Gomes P, Soares-da-Silva P (1999) L-DOPA transport properties in an immortalised cell line of rat capillary cerebral endothelial cells, RBE 4. Brain Res 829:143–150
Ikeda-Matsuo Y, Ota A, Fukada T, Uematsu S, Akira S, Sasaki Y (2006) Microsomal prostaglandin E synthase-1 is a critical factor of stroke-reperfusion injury. Proc Natl Acad Sci USA 103:11790–11795
Kageyama T, Nakamura M, Matsuo A, Yamasaki Y, Takakura Y, Hashida M, Kanai Y, Naito M, Tsuruo T, Minato N, Shimohama S (2000) The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier. Brain Res 879:115–121
Koyama Y, Matsui S, Itoh S, Osakada M, Baba A, Matsuda T (2004) The selective Na+-Ca2+ exchange inhibitor attenuates brain edema after radiofrequency lesion in rats. Eur J Pharmacol 489:193–196
Momma S, Aoyagi M, Rapoport SI, Smith QR (1987) Phenylalanine transport across the blood-brain barrier as studied with the in situ brain perfusion technique. J Neurochem 48:1291–1300
Murakami H, Takanaga H, Matsuo H, Ohtani H, Sawada Y (2000) Comparison of blood-brain barrier permeability in mice and rats using in situ brain perfusion technique. Am J Physiol Heart Circ Physiol 279:H1022–H1028
Redzic Z (2011) Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS 8:3
Suzuki T, Oshimi M, Tomono K, Hanano M, Watanabe J (2002) Investigation of transport mechanism of pentazocine across the blood-brain barrier using the in situ rat brain perfusion technique. J Pharm Sci 91:2346–2353
Acknowledgments
This work was supported in part by a Grant-in-Aid for Scientific Research (C) (KAKENHI #22590149) to T.S. from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and a grant from the “High-Tech Research Center” Project for Private Universities: matching fund subsidy from MEXT in 2007–2011 (to T.S and T.F.).
Conflict of InterestWe declare that we have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Wien
About this paper
Cite this paper
Suzuki, T. et al. (2013). Blood–Brain Barrier Transport of an Essential Amino Acid After Cerebral Ischemia Reperfusion Injury. In: Katayama, Y., Maeda, T., Kuroiwa, T. (eds) Brain Edema XV. Acta Neurochirurgica Supplement, vol 118. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1434-6_58
Download citation
DOI: https://doi.org/10.1007/978-3-7091-1434-6_58
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-1433-9
Online ISBN: 978-3-7091-1434-6
eBook Packages: MedicineMedicine (R0)