Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview

The blood-brain barrier (BBB) is a fundamental component of the central nervous system
(CNS). Its functional and structural integrity is vital to maintain the homeostasis of the brain microenvironment by controlling the passage of substances and regulating the trafficking of immune cells
between the blood and the brain. The BBB is primarily composed of highly specialized microvascular endothelial cells. These cells’ special features and physiological properties are acquired and
maintained through the concerted effort of hemodynamic and cellular cues from the surrounding
environment. This complex multicellular system, comprising endothelial cells, astrocytes, pericytes,
and neurons, is known as the neurovascular unit (NVU). The BBB strictly controls the transport
of nutrients and metabolites into brain parenchyma through a tightly regulated transport system
while limiting the access of potentially harmful substances via efflux transcytosis and metabolic
mechanisms. Not surprisingly, a disruption of the BBB has been associated with the onset and/or
progression of major neurological disorders. Although the association between disease and BBB
disruption is clear, its nature is not always evident, specifically with regard to whether an impaired
BBB function results from the pathological condition or whether the BBB damage is the primary
pathogenic factor prodromal to the onset of the disease. In either case, repairing the barrier could be
a viable option for treating and/or reducing the effects of CNS disorders. In this review, we describe
the fundamental structure and function of the BBB in both healthy and altered/diseased conditions.
Additionally, we provide an overview of the potential therapeutic targets that could be leveraged to
restore the integrity of the BBB concomitant to the treatment of these brain disorders. CLICK TO REVIEW