Oxidative Stress and Blood–Brain Barrier Dysfunction Under Particular Consideration of Matrix Metalloproteinases

Abstract

A cell's "redox" (oxidation and reduction) state is determined by the sum of all redox processes yielding reactive oxygen species (ROS), reactive nitrogen species (RNS), and other reactive intermediates. Low amounts of ROS/RNS are generated by different mechanisms in every cell and are important regulatory mediators in many signaling processes (redox signaling). When the physiological balance between the generation and elimination of ROS/RNS is disrupted, oxidative/nitrosative stress with persistent oxidative damage of the organism occurs. Oxidative stress has been suggested to act as initiator and/or mediator of many human diseases. The cerebral vasculature is particularly susceptible to oxidative stress, which is critical since cerebral endothelial cells play a major role in the creation and maintenance of the blood-brain barrier (BBB). This article will only contain a focused introduction on the biochemical background of redox signaling, since this has been reported already in a series of excellent recent reviews. The goal of this work is to increase the understanding of basic mechanisms underlying ROS/RNS-induced BBB disruption, with a focus on the role of matrix metalloproteinases, which, after all, appear to be a key mediator in the initiation and progression of BBB damage elicited by oxidative stress.

Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress

“…26,27,29 A host of vascular and neuro-glial substrates are known to regulate the physical, metabolic, and transport barrier properties of BBB via endocrine, paracrine, or autocrine signaling mechanisms. [37][38][39] Brain microvascular endothelial cells are highly sensitive to imbalance in redox homeostasis [40][41][42] and increased endothelial oxidative stress significantly compromises the stringency of BBB with marked reduction in the immunological privilege of CNS. 28,[43][44][45] To this end, compelling evidence suggests that psychostimulants as well as tobacco smoking could have profound pro-oxidant effects and significantly activate endothelial oxidative stress responses, thus, leading to a compromised BBB integrity.…”

Viral Infection of the Central Nervous System and Neuroinflammation Precede Blood-Brain Barrier Disruption during Japanese Encephalitis Virus Infection

“…Together, these proteins and cells form an elaborate network that selectively regulates the transport of the compounds into and out of the brain (7,(9)(10)(11). Cell adhesion molecules (AMs) are cell surface molecules that facilitate intercellular binding and communication (12,13).…”

Enhancement of Blood-Brain Barrier Permeability and Reduction of Tight Junction Protein Expression Are Modulated by Chemokines/Cytokines Induced by Rabies Virus Infection

“…One of the key mechanisms of BBB breakdown is damage to the tight junction (TJ) in the brain microvascular ECs (BMECs) (19). The TJ complex is composed of both transmembrane TJ proteins (occludin and claudins) and cytosolic TJ proteins (zonula occludens-1 [ZO-1]) that link transmembrane TJ proteins to the actin cytoskeleton (21)(22)(23). Many viral infections, such as infections with human immunodeficiency virus (HIV), Japanese encephalitis virus (JEV), and mouse adenovirus type 1 (MAV-1), trigger changes in BBB permeability (24)(25)(26).…”