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Brain Res. 2015 Oct 22;1624:175-187. doi: 10.1016/j.brainres.2015.07.033. Epub 2015 Jul 30.

Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity.

Author information

1
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA.
2
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA. Electronic address: smahajan@buffalo.edu.

Abstract

Methamphetamine (Meth) abuse can lead to the breakdown of the blood-brain barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Our data suggests that Galectin-1 is involved in BBB remodeling and can increase levels of TJ proteins ZO-1 and Claudin-3 and adhesion molecule ICAM-1 which helps maintain BBB tightness thus playing a neuroprotective role. Galectin-1 is thus an important regulator of immune balance from neurodegeneration to neuroprotection, which makes it an important therapeutic agent/target in the treatment of drug addiction and other neurological conditions.

KEYWORDS:

Blood brain barrier; Galectin-1; Human brain microvascular endothelial cells; Methamphetamine; Oxidative stress; Proinflammatory cytokines; Tight junctions; Transendothelial electrical resistance

PMID:
26236024
PMCID:
PMC4630155
DOI:
10.1016/j.brainres.2015.07.033
[Indexed for MEDLINE]
Free PMC Article

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