Abstract
The use of psychostimulants and alcohol disrupts blood-brain barrier (BBB) integrity, resulting in alterations to cellular function, and contributes to neurotoxicity. The BBB is the critical boundary of the central nervous system (CNS) where it maintains intracellular homeostasis and facilitates communication with the peripheral circulation. The BBB is regulated by tight junction (TJ) proteins that closely interact with endothelial cells (EC). The complex TJ protein network consists of transmembrane proteins, including claudins, occludins, and junction adhesion molecules (JAM), as well as cytoskeleton connected scaffolding proteins, zonula occludentes (ZO-1, 2, and 3). The use of psychostimulants and alcohol is known to affect the CNS and is implicated in various neurological disorders through neurotoxicity that partly results from increased BBB permeability. The present mini review primarily focuses on BBB structure and permeability. Moreover, we assess TJ protein and cytoskeletal changes induced by cocaine, methamphetamine, morphine, heroin, nicotine, and alcohol. These changes promote glial activation, enzyme potentiation, and BBB remodeling, which affect neuroinflammatory pathways. Although the effect of drugs of abuse on BBB integrity and the underlying mechanisms are well studied, the present review enhances the understanding of the underlying mechanisms through which substance abuse disorders cause BBB dysfunction.
Highlights
The blood-brain barrier (BBB) is formed by an endothelial cell (EC) monolayer between the blood and central nervous system (CNS) that contributes to maintaining structural and functional homeostasis in the brain
The BBB is formed by an EC network rigidly connected by complex junction systems comprised of smaller trans-membrane tight junction (TJ) proteins, including junction adhesion molecules (JAM), endothelial cell-selective adhesion molecules, occludins, and claudins (Ballabh et al, 2004; Van Itallie and Anderson, 2014)
The BBB is critical to the maintenance of brain homeostasis as it regulates the entry of macromolecules, ions, and neurotransmitters from the blood to the brain (Abbott et al, 2010; Lippmann et al, 2013; Wilhelm and Krizbai, 2014; Erickson and Banks, 2018)
Summary
The blood-brain barrier (BBB) is formed by an endothelial cell (EC) monolayer between the blood and central nervous system (CNS) that contributes to maintaining structural and functional homeostasis in the brain. The BBB is formed by an EC network rigidly connected by complex junction systems comprised of smaller trans-membrane tight junction (TJ) proteins, including junction adhesion molecules (JAM), endothelial cell-selective adhesion molecules, occludins, and claudins (Ballabh et al, 2004; Van Itallie and Anderson, 2014). This creates a boundary between the CNS and peripheral circulation for regulating blood-CNS exchange (Kousik et al, 2012)
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