Table 1.

Diseases in which blood-brain barrier disruption is a hallmark of this disorder and the subsequent involvement of oxidative stress and inflammation.

Disorder	BBB dysfunction	Inflammation and oxidative stress	References
Alzheimer’s Disease	Increased paracellular permeability (MRI, postmortem analysis, increased albumin CSF ratio, TEER, fluorescein). Decreased tight junction proteins claudin-5, occludin, and ZO-1 expression. Degradation of endothelial cells and pericytes. Alterations in thickness of the basement membrane. Astrocyte degeneration. Decreased expression of GLUT1 transporter and decreased levels of low density-lipoprotein receptor-related protein (LRP). Increased expression of receptor for advanced glycan end products (RAGE).	Increased pro-inflammatory cytokines IL-1β, IL-8, TNF. Activated astrocytes. Activated microglia. Leukocyte infiltration. Increased ROS.	[55, 56, 95, 101, 105, 112, 160–169]
Parkinson’s Disease	Increased permeability (Albumin leakage, increase hemoglobin, fibrinogen, 70 kDa FITC, TEER). Decrease in expression of tight junction proteins claudin-5, occludin and ZO-1. Decreased endothelial cells and cell thickness. Increased thickness of the basement membrane. Activation of pericytes. Altered activity and expression of Pgp efflux transporter. Decreased GLUT1 and BCRP expression.	Increased proinflammatory cytokines IL-1 β, IL-2, IL-6, TNF Activated astrocytes. Activated microglia. Leukocyte infiltration. Increased ROS.	[12, 102, 103, 170–175]
Amyotrophic lateral sclerosis	Increased barrier permeability (hemoglobin, increased albumin, Evan’s blue leakage). Decreased abundance of claudin-5, occludin, and ZO-1. Endothelial cell degeneration or damage. Basement membrane changes in PECAM-1 and collagen IV proteins. Altered astrocyte phenotype, astrocyte end-feet capillary damage and dissociation. Pericyte degeneration or damage.	Increased proinflammatory cytokines IL-1β, IL-2, IL-6, IL-10, TNF. Activated astrocytes. Activated microglia. Leukocyte infiltration. Increased ROS.	[176–187]
Multiple Sclerosis	Increased barrier permeability (MRI, Evan’s blue). Reduced expression of tight junction proteins claudin-5, occludin, and ZO-1. Reorganization of actin cytoskeleton. Changes in pericyte morphology and swollen astrocytic end feet.	Increased proinflammatory cytokines IL-2, IL-17, TNF. Activated astrocytes. Activated microglia. Leukocyte infiltration. Increased ROS.	[188–196]
Huntington’s Disease	Increased barrier permeability (MRI, postmortem analysis, increased albumin). Decreased expression of claudin-5 and occludin. Altered pericyte coverage and density. Altered transcellular vesicular transport. Decreased GLUT1 expression on astrocytes. Reduction of pericyte coverage.	Increased proinflammatory cytokines IL-1β, IL-6, IL-8, TNF. Activated astrocytes. Activated microglia. Increased ROS.	[197–206]
Ischemic Stroke	Increased barrier permeability (sucrose leakage, Evan’s blue, MRI). Decreased expression of tight junction proteins claudin-5, occludin, and ZO-1. Degraded basement membrane. Swollen astrocytic end-feet. Increased GLUT1 expression. Alterations in solute carrier expression. Increased vesicular transport.	Increased proinflammatory cytokines IL-1β, IL-6, TNF. Activated astrocytes. Activated microglia. Leukocyte infiltration. Increased ROS.	[9, 46, 50, 207–212]