The biological significance of brain barrier mechanisms: help or hindrance in drug delivery to the central nervous system?

• DOI: 10.12688/f1000research.7378.1
• Publication Date: 2016-03-10T06:05:38Z
• Authors: Norman R. Saunders; Mark D. Habgood; Kjeld Møllgård; Katarzyna M. Dzie...
• Keywords: Circumventricular organs; Ependyma; Neuroepithelial cell; Vesicular Transport Proteins

Barrier mechanisms in the brain are important for its normal functioning and development. Stability of brain's internal environment, particularly with respect to ionic composition, is a prerequisite fundamental basis function, namely transmission nerve impulses. In addition, appropriate controlled supply wide range nutrients such as glucose, amino acids, monocarboxylates, vitamins also essential development function. These all cellular functions across interfaces that separate from rest environment body. An morphological component but one barriers presence specialized intercellular tight junctions between cells comprising interface: endothelial blood-brain barrier itself, arachnoid membrane, choroid plexus epithelial cells, tanycytes (specialized glial cells) circumventricular organs. ependyma lining cerebral ventricles adult brain, joined by gap junctions, which not restrictive movement molecules. But developing forerunners these form neuroepithelium, restricts exchange smallest molecules cerebrospinal fluid interstitial because strap cells. The physical their properties. proper, this combined paucity vesicular transport characteristic other vascular beds. Without diffusional restrain, would be ineffective. Superimposed on structures physiological contain various metabolic transporters efflux pumps, often ATP-binding cassette (ABC) transporters, provide an either preventing entry or expelling numerous including toxins, drugs, xenobiotics. review, we summarize influx well indicating likely involvement neuropathologies. There have been extensive attempts overcome prevent many drugs therapeutic potential into brain. We outline those tried discuss why they may so far largely unsuccessful. Currently, promising approach appears focal, reversible disruption using focused ultrasound, more work required evaluate method before it can patients. Overall, our view much knowledge new experimental methods will drug targeting successful endeavor. studies, if applied pathologies stroke, trauma, multiple sclerosis, aid defining contribution pathology conditions, causative secondary.