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

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.

Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells

“…BBB impairment by METH has been reviewed in several mechanisms, including the hyperactivity of NADPH oxidase (NOX)-2 which generates excessive amounts of free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) (Ramirez et al, 2009;Park et al, 2012); the dysfunction of cytoskeleton and the trans-membrane protein of tight junction, which is the controlling of paracellular permeability (Park et al, 2013;Fernandes et al, 2015); the dysfunction of the uptake and the efflux activities (ElAli et al, 2012); and the activation of caspase cascade in cell death response or apoptosis (Abdul-Muneer et al, 2011;Ma et al, 2014;Fisehr et al, 2015). Moreover, overexpression of inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), interleukin (IL)-1, and tumor necrosis factor (TNF), which is an important factor in inflammatory response, has also been reported (Fernandes et al, 2014;CoelhoSantos et al, 2015;Parikh et al, 2015;Zhang et al, 2015;Skaper et al, 2014;Husain et al, 2015;Kothur et al, 2015). Previous studies have demonstrated that the release of cytokines causes progressive BBB impairment by the upregulation of leukocyte-endothelial cell adhesion molecules such as intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, and matrix metallopeptidase (MMP)-9 leads to tight junction impairment (Urrutia et al, 2013;Fernandes et al, 2014;Wang et al, 2014aWang et al, , 2014bParikh et al, 2015).…”

“…Moreover, overexpression of inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), interleukin (IL)-1, and tumor necrosis factor (TNF), which is an important factor in inflammatory response, has also been reported (Fernandes et al, 2014;CoelhoSantos et al, 2015;Parikh et al, 2015;Zhang et al, 2015;Skaper et al, 2014;Husain et al, 2015;Kothur et al, 2015). Previous studies have demonstrated that the release of cytokines causes progressive BBB impairment by the upregulation of leukocyte-endothelial cell adhesion molecules such as intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, and matrix metallopeptidase (MMP)-9 leads to tight junction impairment (Urrutia et al, 2013;Fernandes et al, 2014;Wang et al, 2014aWang et al, , 2014bParikh et al, 2015). The impairment of tight junction of BBB reduces transendothelial electric resistance (TEER) values and the expression of tight junction proteins such as ZO-1, occludin, and claudin-5, leading to increased paracellular permeability (Mahajan et al, 2008;Rosas-Hernandez et al, 2013).…”

WITHDRAWN: Melatonin improves methamphetamine-induced blood brain barrier impairment through NADPH oxidase-2 in primary rat brain microvascular endothelium cells

“…BBB impairment by METH has been reviewed in several mechanisms, including the hyperactivity of NADPH oxidase (NOX)-2 which generates excessive amounts of free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) (Ramirez et al, 2009;Park et al, 2012); the dysfunction of cytoskeleton and the transmembrane protein of tight junction, which is the controlling of paracellular permeability (Park et al, 2013;Fernandes et al, 2015); the dysfunction of the uptake and the efflux activities (Elali et al, 2012); and the activation of caspase cascade in cell death response or apoptosis (Abdul et al, 2011;Ma et al, 2014;Fisher et al, 2015). Moreover, overexpression of inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO), interleukin (IL)-1, and tumor necrosis factor (TNF) α, which is an important factor in inflammatory response, has also been reported (Fernandes et al, 2014;Coelho-Santos et al, 2015;Parikh et al, 2015;Zhang et al, 2015;Skaper et al, 2014;Hussain et al, 2015;Kothur et al, 2015).…”

“…Previous studies have demonstrated that the release of cytokines causes progressive BBB impairment by the activation of leukocyte infiltration and monocyte adhesion molecules such as intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, and matrix metallopeptidase (MMP)-9 leads to tight junction impairment (Urrutia et al, 2013;Fernandes et al, 2014;Parikh et al, 2015). Decrease in the levels of tight junction proteins such as ZO-1, occludin, and claudin-5 are associated with BBB dysfunction and increased paracellular permeability, leading to decrease transendothelial electric resistance (TEER) values (Mahajan et al, 2008;Rosas-Hernandez et al, 2013).…”

Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells

“…The low permeability of the BBB is effected by tight junctions (TJ) between brain endothelial cells [13], but these TJs can be affected by a variety of molecules including reactive oxygen species (ROS) and nitric oxide (NO) [14]. In this regard, the toxic effects of METH on the BBB have been studied both in vitro [15, 16] and in vivo [17-20]. METH induces an increase in BBB permeability as evidenced using an in vitro model, bovine brain microvessel endothelial cells (bBMVECs).…”