%0 Journal Article
%T Multiple Sclerosis and the Blood-Central Nervous System Barrier
%A Alan M. Palmer
%J Cardiovascular Psychiatry and Neurology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/530356
%X The central nervous system (CNS) is isolated from the blood system by a physical barrier that contains efflux transporters and catabolic enzymes. This blood-CNS barrier (BCNSB) plays a pivotal role in the pathophysiology of multiple sclerosis (MS). It binds and anchors activated leukocytes to permit their movement across the BCNSB and into the CNS. Once there, these immune cells target particular self-epitopes and initiate a cascade of neuroinflammation, which leads to the breakdown of the BCNSB and the formation of perivascular plaques, one of the hallmarks of MS. Immunomodulatory drugs for MS are either biologics or small molecules, with only the latter having the capacity to cross the BCNSB and thus have a propensity to cause CNS side effects. However, BCNSB penetration is a desirable feature of MS drugs that have molecular targets within the CNS. These are nabiximols and dalfampridine, which target cannabinoid receptors and potassium channels, respectively. Vascular cell adhesion molecule-1, present on endothelial cells of the BCNSB, also serves as a drug discovery target since it interacts with ¦Á4-¦Â1-integrin on leucocytes. The MS drug natalizumab, a humanized monoclonal antibody against ¦Á4-¦Â1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS. 1. Introduction Multiple sclerosis (MS) is an acquired autoimmune disease that affects both the brain and the spinal cord leading to a variety of symptoms, including changes in motor function, sense perception, and mental function, along with fatigue [1¨C3]. The disease presents in different forms that follow distinct patterns of evolution and rates of disability progression [4]. The most common form is relapsing-remitting MS (RRMS), which affects about 85% of people with MS (pwMS), is more common in females than males (by a ratio of 2 to 1), and has an average age at diagnosis of 29 years [5]. RRMS is characterized by acute attacks (relapses) followed by partial or full recovery (remission) and contrasts with primary progressive MS (PPMS), which affects about 10¨C15% of pwMS, is diagnosed (on average) at age 40, has no gender bias, and is characterized by a steady and irreversible progression of functional impairments [6¨C8]. These two forms of MS also differ in their onset as PPMS begins insidiously, whereas the harbinger of RRMS is usually a transient impairment in motor or sensory function, together with white matter abnormalities shown by magnetic resonance
%U http://www.hindawi.com/journals/cpn/2013/530356/