Nitric Oxide and Blood–Brain Barrier Integrity

The blood-brain barrier (BBB) is comprised of the endothelial cells that line the capillaries of the brain. The unique characteristics of this barrier include tight intercellular junctions, a complex glycocalyx, a paucity of pinocytic vesicles, and an absence of fenestra. These properties allow for the selective exchange of substances between the systemic circulation and the extracellular fluid compartment of the brain. It is well established that there are many conditions, including those mediated by nitric oxide (NO), that can lead to an opening of the BBB, eventually leading to vasogenic edema and secondary brain damage. The precise molecular mechanisms mediating NO-induced tissue injury and the breakdown of the BBB are complex and not completely understood. NO is a soluble, easily diffusible gas that is generated by NO synthase. Two of the isoforms of NO synthase are constitutive, calcium-dependent enzymes that modulate many physiological functions, including the regulation of smooth muscle contraction and blood flow. The third isoform is calcium-independent and inducible and can be stimulated by stress, inflammation, and infection. Under these conditions, NO can be generated in large quantities and has detrimental effects on the CNS. NO has been shown to increase permeability of the BBB, allowing substances to enter into the brain passively. This review considers the role of NO and BBB integrity.