ABSTRACT
It is an irrefutable fact that the brain is connected to the rest of the body by the circulation, and maintenance of this connection throughout life is essential for normal brain function. To prevent infl ux of blood, serum and other proteins, ions and water into the brain, the blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB) have developed, involving a series of complex molecular structures that result in strong interactions of brain microvascular endothelial cells (BMEC) with each other. The formation of the BBB is regulated by factors produced by the other cellular components of the neurovascular unit (NVU), particularly pericytes and astrocytes, but supported by microglia, neurons and perivascular macrophages. In addition to the “tightness” of the cellular interactions to prevent leakage into the brain, BMEC contain many different transporter systems that allow the brain to receive high infl ux of nutrients and oxygen and remove unwanted waste materials, while keeping out peripheral toxins or microorganisms and many pharmacological agents. For the majority of life, this system keeps most humans healthy and permits the brain to function normally. With
Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, Arizona, USA. Email: lihfen.lue@bannerhealth.com * Corresponding author: douglas.walker@bannerhealth.com
aging, and the development of chronic neurodegenerative diseases, the BBB/BSCB starts to be compromised and in some circumstances becomes leaky. If one considers BBB breakdown from the point of view of acute ischemia or hemorrhage (stroke), there are signifi cant and immediate neurological consequences of BBB compromise. This is a separate area of study; for this chapter, we will focus on various changes in the cerebrovasculature and BBB that seem to occur in Alzheimer’s disease (AD) and Parkinson’s disease (PD), the two most signifi cant chronic neurodegenerative diseases of aging. In addition, we will consider for amyotrophic lateral sclerosis (ALS), breakdown of the BSCB. In all of these diseases, BBB/BSCB compromise is believed to exacerbate, and could even initiate, the pathological changes of neuronal damage and loss that contribute to clinical manifestations of these diseases.
