Before a discussion of the role of nitric oxide in the permeability characteristics of the blood-brain barrier, it is important to understand the evolution of our understanding of the blood-brain barrier. More than a century ago Ehrlich found that intravascular injection of dye distributed relatively equally throughout the most tissues of the body, with the exception of the brain. From these studies, Ehrlich concluded that the brain had a lower affinity for the dye than peripheral tissues. However, studies by Goldmann found that dye injected into the circulation stained all tissues except that of brain and spinal cord. Further, when the dye was injected into the cerebrospinal fluid, it stained the brain but did not enter the peripheral circulation. Thus, these discoveries led to the concept that the central nervous system must be separated from the peripheral circulation by some type of barrier, that is, the blood-brain barrier. However, the identity of the ultrastructure of this barrier remained unknown for nearly 50 years.
Since astrocytes were shown to encapsulate cerebral capillaries, it was initially thought that astrocytes composed the blood-brain barrier. With the arrival of the electron microscope, it became clear that structures within cerebral blood vessels, and not astrocytes, constituted the blood-brain barrier. These structures consist of tight junctions between adjacent endothelial cells (i.e., zonulae occludens). In addition, endothelial cells of cerebral vessels are devoid of fenestra-tions and transendothelial channels and have a paucity of pinocytotic vesicles. Because of its morphology, it was initially thought that the blood-brain barrier was a very static and rigid structure separating the brain from the peripheral environment. However, this view of the blood-brain barrier has evolved over the years, and it is now known that the blood-brain barrier is a dynamic and multifaceted structure that contains important transport pathways and complex enzyme systems that participate in the regulation of the brain's microenvironment.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.