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Effects of hepatic ischemia-reperfusion injury on the blood-brain barrier permeability to [14C] and [13C]sucrose

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Abstract

Hepatic encephalopathy that is associated with severe liver failure may compromise the blood-brain barrier (BBB) integrity. However, the effects of less severe liver diseases, in the absence of overt encephalopathy, on the BBB are not well understood. The goal of the current study was to investigate the effects of hepatic ischemia-reperfusion (IR) injury on the BBB tight junction permeability to small, hydrophilic molecules using the widely used [14C]sucrose and recently-proposed alternative [13C]sucrose as markers. Rats were subjected to 20 min of hepatic ischemia or sham surgery, followed by 8 h of reperfusion before administration of a single bolus dose of [14C] or [13C]sucrose and collection of serial (0–30 min) blood and plasma and terminal brain samples. The concentrations of [14C] and [13C]sucrose in the samples were determined by measurement of total radioactivity (nonspecific) and LC-MS/MS (specific), respectively. IR injury significantly increased the blood, plasma, and brain concentrations of both [14C] and [13C]sucrose. However, when the brain concentrations were corrected for their respective area under the blood concentration-time curve, only [14C]sucrose showed significantly higher (30%) BBB permeability values in the IR animals. Because [13C]sucrose is a more specific BBB permeability marker, these data indicate that our animal model of hepatic IR injury does not affect the BBB tight junction permeability to small, hydrophilic molecules. Methodological differences among studies of the effects of liver diseases on the BBB permeability may confound the conclusions of such studies.

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Acknowledgements

The Authors would like to thank Dr. Raktima Bhattacharya from Texas Tech University School of Pharmacy for assistance with the radiolabeled studies.

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  1. Mohammad K. Miah

    Present address: School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA

    Mohammad K. Miah, Ulrich Bickel & Reza Mehvar

  2. Center for Blood-Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, TX, USA

    Ulrich Bickel & Reza Mehvar

  3. Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, 9401 Jeronimo Road, Irvine, CA, USA

    Reza Mehvar

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  1. Mohammad K. Miah
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Contributions

MKM, UB, and RM designed the experiments, analyzed the data and wrote the manuscript. MKM performed the experiments.

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Correspondence to Ulrich Bickel or Reza Mehvar.

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The authors declare that they do not have any conflict of interest.

Grant support

Financial support for this study was provided by the Center for Blood–Brain Barrier Research at Texas Tech School of Pharmacy.

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Miah, M.K., Bickel, U. & Mehvar, R. Effects of hepatic ischemia-reperfusion injury on the blood-brain barrier permeability to [14C] and [13C]sucrose. Metab Brain Dis 32, 1903–1912 (2017). https://doi.org/10.1007/s11011-017-0069-2

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  • DOI: https://doi.org/10.1007/s11011-017-0069-2

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