Past and Recent BBB Studies with Particular Emphasis on Changes in Ischemic Brain Edema
The blood-brain barrier (BBB) functions to protect the environment of the brain through endothelial cells and their interactions with other cells and components of the cerebral vasculature and the brain parenchyma. Alterations in the BBB as a result of in
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Abstract The blood-brain barrier (BBB) functions to protect the environment of the brain through endothelial cells and their interactions with other cells and components of the cerebral vasculature and the brain parenchyma. Alterations in the BBB as a result of injuries (i.e., brain ischemia and traumatic brain injury) play a crucial role in the pathophysiological response. The following is a brief review of the BBB and the mechanisms by which its cellular elements participate in barrier disruptions such as those associated with ischemia and resulting brain edema formation. Keywords Blood-brain barrier (BBB) • neurovascular unit • ischemia • brain edema
Introduction The blood brain barrier (BBB) is a physical and metabolic barrier between systemic blood circulation and the central nervous system (CNS). This concept originated over a hundred years ago when Paul Erlich and subsequently E. E. Goldman published studies demonstrating a limited penetration of certain substances (i.e., dyes) from blood to brain and from brain to blood (see review 21). Present notion about the CNS includes other barriers (i.e., bloodcerebrospinal fluid (BCSF) and blood-retinal barrier (BRB)). The morphologic localization of the barriers was advanced by light microscopy and electron microscopy using contrast media (i.e., horseradish peroxidase, etc.). The capillary endothelium in the brain and retina was
M. Spatz (*) Stroke Branch, NINDS National Institutes of Health, Bethesda, MD, 20892, USA e-mails: [email protected]; [email protected]
demonstrated at the site of the BBB and BRB, whereas the choroid plexus represents the site of BCSF. Many additional studies showed that the passage of substances through the BBB depends on the size and lipid solubility. It has also been demonstrated that non-diffusible polar substances (such as nutrients) require specific transporters to cross this barrier. These transporters were characterized as facilitated or active (energy-linked to ATP) transporters dependent on the given substance’s intrinsic requirement namely it’s downhill or uphill concentration gradient. In addition, both in vivo and in situ studies showed the existence of a metabolic barrier (i.e., enzymatic) provided by endothelial cells that limits the passage of molecules from blood to brain and brain to blood. These observations were reinforced and advanced by the ability to separate the capillaries and microvessels from the rest of the brain parenchyma as well as the subsequent culturing of endothelial cells and other brain cells. It became evident that the cerebrovascular tree represents a separate and distinct biochemically active compartment. Moreover, the understanding of the BBB has been increased by the recently acquired molecular insight into its structural components. This function has been attributed to the endothelial cells, the main constituent of the BBB. Thus, these cells originally thought of as physical barrier were shown to have a variety of biological activities that were responsible for BBB properties and co
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