What is it about?

The cytotoxic effects of methamphetamine (MA) are well established to be caused via induced oxidative stress which in turn compromises the core function of the blood-brain barrier by reducing its ability to regulate the homeostatic environment of the brain. While most studies were conducted over a period of 24-48 hours, this study investigated the mechanisms by which chronic exposure of MA adversely affects the endothelial cells of blood-brain barrier over an extended period of 96 hours. MA induced significant depression of cell numbers at 96 hrs. This result was supported by flow cytometric data on the cell cycle which showed that brain endothelial cells (bEnd5) at 96 hours were significantly suppressed in the S phase of the cell cycle. In contrast, at 24-72 hrs control cell numbers for G1, S and G2-M phases were similar to MA exposed cells. MA (0-1000μM) did not, however, statistically affect the viability and cytotoxicity of the bEnd5 cells, and the profile of ATP production and DNA synthesis (BrdU) across 96 hrs did not provide a rationale for the suppression of cell division.

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Why is it important?

Our study reports for the first time that chronic exposure to MA results in long-term disruption of the cell cycle phases which eventuates in the attenuation of brain capillary endothelial cell growth after 96 hrs, compounding and contributing to the already well known adverse short-term permeability effects of MA exposure on the BBB.

Perspectives

Methamphetamine addiction is a global problem. Our research highlights the danger for both the addict and also for the party user (episodic user) in that the drug blocks cell division of brain cells for up to 4 days after exposure.

Prof David Fisher
University of the Western Cape

Read the Original

This page is a summary of: Methamphetamine is not Toxic but Disrupts the Cell Cycle of Blood–Brain Barrier Endothelial Cells, Neurotoxicity Research, February 2015, Springer Science + Business Media,
DOI: 10.1007/s12640-015-9520-5.
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