Current Pharmaceutical Design - Volume 14, Issue 16, 2008

Over 100 years ago, experiments were conducted that showed an inability of selected blood-borne substances to enter the central nervous system (CNS). These experiments served as the basis of the concept of a blood-brain barrier (BBB). Research in subsequent decades expanded our understanding of the blood-brain barrier. The last 40 years in particular has elucidated the ultrastructural basis for the restrictive aspect Read More

Before entering the central nervous system (CNS) immune cells have to penetrate any one of its barriers, namely either the endothelial blood-brain barrier, the epithelial blood-cerebrospinal fluid barrier or the tanycytic barrier around the circumventricular organs, all of which maintain homeostasis within the CNS. The presence of these barriers in combination with the lack of lymphatic vessels and the absence of classic Read More

The blood-brain barrier becomes a crucial issue in neuronopathic lysosomal storage diseases for three reasons. Firstly, the function of the blood-brain barrier may be compromised in many of the lysosomal storage diseases and this barrier dysfunction may contribute to the neuropathology seen in the diseases and accelerate cell death. Secondly, the substrate reduction therapies, which successfully reduce peripheral lysoso Read More

Pericytes were described nearly 140 years ago by the French scientist Charles-Marie Benjamin Rouget and were referred to as the Rouget cell. The Rouget cell was renamed primarily due to its anatomical location in the endothelium. Pericytes are important cellular constituents of the capillaries and post capillary venules and are located abluminal to the endothelial cells and luminal to parenchymal cells. They deposit elements of Read More

From a complications standpoint, diabetes mellitus is a disease of the vasculature. Diabetics face a considerably higher risk of developing cardiovascular and cerebrovascular diseases. Both large and small blood vessels are susceptible to alterations from diabetes. Endothelial cell dysfunction associated with small vessel (known as microangiopathy) is a primary factor in the development and progression of diabete Read More

Low-density lipoprotein receptor related protein-1 (LRP) is a member of the low-density lipoprotein (LDL) receptor family which has been linked to Alzheimer's disease (AD) by biochemical and genetic evidence. Levels of neurotoxic amyloid β-peptide (Aβ) in the brain are elevated in AD contributing to the disease process and neuropathology. Faulty Aβ clearance from the brain appears to mediate focal Aβ accumulations Read More

The dramatic increase in the number of obese and overweight persons has spurred interest in control of appetite, body weight, and adiposity. Leptin is the humoral component of a negative feedback loop between adipose tissue and brain. Leptin is secreted from fat in proportion to the degree of adiposity, is transported across the blood-brain barrier (BBB), and acts in the brain to decrease appetite and increase thermo Read More

The two main ways for peptides in the peripheral body to enter the brain are by either saturable transport or passive diffusion across the blood-brain barrier (BBB). Saturable transport systems have the advantage of being responsive to physiological and pathological stimuli. Since saturable systems can regulate peptide entry into the brain, they have the potential to play controlling roles in feeding behavior. For therapeutic a Read More

Spinal cord injury (SCI) induces dynamic changes of the blood-spinal cord barrier and even the more distant blood-brain barrier. Besides an immediate increase of paracellular permeability resulting from the direct impact of the injury, the transport systems for selective cytokines undergo regulatory changes. Since many of the transported molecules play essential roles in neuroregeneration, we propose that this al Read More

Pain is a complex phenomenon involving both a peripheral innate immune response and a CNS response as well as activation of the hypothalamic-pituitary-adrenal axis. The peripheral innate immune response to injury involves the rapid production and local release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and IL-6. Recent studies into the CNS response to peripheral c Read More