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Effects of Volatile Anesthetics versus Ketamine on Blood-Brain Barrier Permeability via Lipid-Mediated Alterations of Endothelial Cell Membranes.
Noorani, Behnam; Chowdhury, Ekram Ahmed; Alqahtani, Faleh; Ahn, Yeseul; Nozohouri, Ehsan; Zoubi, Sumaih; Patel, Dhavalkumar; Wood, Laurence; Huang, Juyang; Siddique, Muhammad Bilal; Al-Ahmad, Abraham; Mehvar, Reza; Bickel, Ulrich.
Afiliação
  • Noorani B; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Chowdhury EA; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Alqahtani F; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Ahn Y; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Nozohouri E; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Zoubi S; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Patel D; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Wood L; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Huang J; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Siddique MB; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Al-Ahmad A; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Mehvar R; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
  • Bickel U; Department of Pharmaceutical Sciences (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., U.B.), Center for Blood-Brain Barrier Research, (B.N., E.A.C., F.A., Y.A., E.N., S.Z., A.A.-A., R.M., U.B.), and LC-MS Core Facility (D.P.), Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences
J Pharmacol Exp Ther ; 385(2): 135-145, 2023 05.
Article em En | MEDLINE | ID: mdl-36828631
ABSTRACT
The purpose of this study was to investigate the effects of the volatile anesthetic agents isoflurane and sevoflurane, at clinically relevant concentrations, on the fluidity of lipid membranes and permeability of the blood-brain barrier (BBB). We analyzed the in vitro effects of isoflurane or ketamine using erythrocyte ghosts (sodium fluorescein permeability), monolayers of brain microvascular endothelial cells ([13C]sucrose and fluorescein permeability), or liposomes (fluorescence anisotropy). Additionally, we determined the effects of 30-minute exposure of mice to isoflurane on the brain tight junction proteins. Finally, we investigated in vivo brain uptake of [13C]mannitol and [13C]sucrose after intravenous administration in mice under anesthesia with isoflurane, sevoflurane, or ketamine/xylazine in addition to the awake condition. Isoflurane at 1-mM and 5-mM concentrations increased fluorescein efflux from the erythrocyte ghosts in a concentration-dependent manner. Similarly, in endothelial cell monolayers exposed to 3% (v/v) isoflurane, permeability coefficients rose by about 25% for fluorescein and 40% for [13C]sucrose, whereas transendothelial resistance and cell viability remained unaffected. Although isoflurane caused a significant decrease in liposomes anisotropy values, ketamine/xylazine did not show any effects. Brain uptake clearance (apparent Kin) of the passive permeability markers in vivo in mice approximately doubled under isoflurane or sevoflurane anesthesia compared with either ketamine/xylazine anesthesia or the awake condition. In vivo exposure of mice to isoflurane did not change any of the brain tight junction proteins. Our data support membrane permeabilization rather than loosening of intercellular tight junctions as an underlying mechanism for increased permeability of the endothelial cell monolayers and the BBB in vivo. SIGNIFICANCE STATEMENT The blood-brain barrier controls the entry of endogenous substances and xenobiotics from the circulation into the central nervous system. Volatile anesthetic agents like isoflurane alter the lipid structure of cell membranes, transiently facilitating the brain uptake of otherwise poorly permeable, hydrophilic small molecules. Clinical implications may arise when potentially neurotoxic drugs gain enhanced access to the central nervous system under inhalational anesthetics.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anestésicos Inalatórios / Isoflurano / Ketamina / Anestésicos Limite: Animals Idioma: En Revista: J Pharmacol Exp Ther Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Anestésicos Inalatórios / Isoflurano / Ketamina / Anestésicos Limite: Animals Idioma: En Revista: J Pharmacol Exp Ther Ano de publicação: 2023 Tipo de documento: Article