Triggers and Effectors of Oxidative Stress at Blood-Brain Barrier Level: Relevance for Brain Ageing and Neurodegeneration

Table 1

Expression of tight junction proteins in various cellular models of oxidative stress.

BBB in vitro; model	Type of experiment	Special conditions	Documentation of BBB permeability increase	Tight junction proteins alterations	Reference
BBMEC monolayers	Hypoxic stress	Glial conditioned-media treatment	Permeability studies with [14]-sucrose	Claudin-1 shows a significant increase following hypoxic stress	[21]
BBMEC monolayers	Hypoxia/reoxygenation	none	TEER measurements and [14]-sucrose transfer across the barrier	Significant increase in expression; of occludin, ZO-1, and ZO-2	[131]
Rat GP8/3.9 cells	ROS generating environment by a mixture of xanthine oxidase and hypoxanthine	—	TEER; FITC-dextran permeability across the barrier	Decrease of occludin and claudin-5 expression after exposure to oxidative environment	[103]
PBMEC	Hypoxia	Coculture with astrocytes/C6 glioma cells	TEER and passage of [3H]inulin	Decreased ZO-1 immunoreactivity; at regions of cell-cell contact	[43]
BMVECs on a 8.0 𝜇m matrigel-based insert	MMPs aggression	Coculture with leukemic cells	40 kDa dextran-FITC flux by flow cytometry analysis	Downregulation of ZO-1, claudin-5, and occludin	[132]
hCMEC/D3 (immortalized human BEC line)	A𝛽 peptides treatments	—	permeability to the paracellular tracer 70 kD FITC-dextran	Decrease in the occludin level, whereas claudin-5 and ZO-1 were unaffected	[85]
Human BMVEC	Exposure to ROS	—	TEER and monocytes migration studies	Decreased occludin and ZO-1 total content, whereas claudin-5 expression depended on the type of stressor used	[91]

BBMEC: bovine brain microvessel endothelial cells.
TEER: transendothelial electrical resistance.
PBMEC: primary cultures of porcine brain-derived microvascular endothelial cells.
BMVEC: brain microvascular endothelial cells.
ROS: reactive oxygen species.
MMPs: matrix metalloproteinases.