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The blood-brain barrier and methamphetamine: open sesame?

Turowski, P; Kenny, BA; (2015) The blood-brain barrier and methamphetamine: open sesame? Frontiers in Neuroscience , 9 , Article 156. 10.3389/fnins.2015.00156. Green open access

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Abstract

The chemical and electrical microenvironment of neurons within the central nervous system is protected and segregated from the circulation by the vascular blood-brain barrier. This barrier operates on the level of endothelial cells and includes regulatory crosstalk with neighboring pericytes, astrocytes, and neurons. Within this neurovascular unit, the endothelial cells form a formidable, highly regulated barrier through the presence of inter-endothelial tight junctions, the absence of fenestrations, and the almost complete absence of fluid-phase transcytosis. The potent psychostimulant drug methamphetamine transiently opens the vascular blood-brain barrier through either or both the modulation of inter-endothelial junctions and the induction of fluid-phase transcytosis. Direct action of methamphetamine on the vascular endothelium induces acute opening of the blood-brain barrier. In addition, striatal effects of methamphetamine and resultant neuroinflammatory signaling can indirectly lead to chronic dysfunction of the blood-brain barrier. Breakdown of the blood-brain barrier may exacerbate the neuronal damage that occurs during methamphetamine abuse. However, this process also constitutes a rare example of agonist-induced breakdown of the blood-brain barrier and the adjunctive use of methamphetamine may present an opportunity to enhance delivery of chemotherapeutic agents to the underlying neural tissue.

Type: Article
Title: The blood-brain barrier and methamphetamine: open sesame?
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fnins.2015.00156
Publisher version: http://dx.doi.org/10.3389/fnins.2015.00156
Language: English
Additional information: © 2015 Turowski and Kenny. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: CNS chemotherapy, blood-brain barrier, endothelial cell, methamphetamine, neuroinflammation, neurovascular unit, pinocytosis, tight junctions
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1471641
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