Journal Article

Engaging neuroscience to advance translational research in brain barrier biology

Neuwelt, Edward A., Povlishock, John T., Saunders, Norman R., Drewes, Lester R., Fricker, Gert, Molnár, Zoltán, Leybaert, Luc, Janigro, Damir, Iadecola, Constantino, Fahlke, Christoph, O'Donnell, Martha E., Sharp, Frank, Bauer, Björn, Watts, Ryan J., Stanimirovic, Danica

2011

Overview

Key Points Summary points that barrier scientists and neuroscientists need to collaborate on: The neurovascular unit (NVU; comprising cellular and acellular elements of brain vessels, parenchymal cells and peripheral immune cells) incorporates three main functionalities — blood–brain barrier, neuroimmune axis and regulation of the cerebral blood flow — that are tightly integrated in brain physiology and play a part in the pathogenesis of numerous neurological diseases. Exchange of information, nutrients and molecules between systemic and central compartments is controlled by the myriad of NVU transporters, which become dysfunctional in brain diseases such as epilepsy, brain tumours and Alzheimer's disease. Targeting the intracellular signalling pathways that regulate selective blood–brain barrier transporters can potentially be used to enhance brain drug delivery, protect the brain from xenobiotics and prevent the pathogenesis and/or slow the progression of CNS diseases. Neurogenesis and angiogenesis are co-regulated in embryonic and adult brains and are often controlled by the same classes of mediators. Novel methods for co-ordinated stimulation of both neuronal and vascular regeneration will be essential to develop successful brain repair strategies. Progress in understanding and treating brain disease is contingent upon better understanding of the integral function of the NVU in disease, advancing the means to interrogate molecular and functional aspects of the NVU, and the development of strategies to deliver therapeutics across the blood–brain barrier. New high resolution imaging techniques are providing stubstantial advances in the blood–brain barrier field and have a powerful potential for further progress. In particular, in vivo two-photon imaging studies of interactions of glial cells and blood cells with the blood–brain barrier are required to compose an integrated picture of blood–brain barrier regulation and function. A great many aspects of neuronal physiology and pathology involve or affect the brain barriers. Recent insights into the role of the blood–brain barrier during development, and advances in our understanding of how it affects neurological disorders, have led to closer links between the two topics. The delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by brain barriers, of which the most well known are the blood–brain barrier (BBB) and the blood–cerebrospinal fluid (CSF) barrier. Recent studies have shown numerous additional roles of these barriers, including an involvement in neurodevelopment, in the control of cerebral blood flow, and — when barrier integrity is impaired — in the pathology of many common CNS disorders such as Alzheimer's disease, Parkinson's disease and stroke.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/1341 / 631/378/1697 / 692/308/575 / Alzheimer's disease / Animal Genetics and Genomics / Animals / Behavioral Sciences / Biological and medical sciences / Biological Techniques / Biological Transport - physiology / Biomedical and Life Sciences / Biomedicine / Blood / Blood-brain barrier / Blood-Brain Barrier - drug effects / Blood-Brain Barrier - metabolism / Brain - drug effects / Brain - metabolism / Brain research / Cerebral circulation / Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges / Cerebrovascular Circulation - drug effects / Cerebrovascular Circulation - physiology / Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases / Diagnosis / Disease / Endothelium / Fundamental and applied biological sciences. Psychology / Humans / Interdisciplinary aspects / Medical sciences / Nervous system diseases / Nervous System Diseases - drug therapy / Nervous System Diseases - metabolism / Neurobiology / Neurology / Neuroprotective Agents - metabolism / Neuroprotective Agents - therapeutic use / Neurosciences / Neurosciences - methods / Neurosciences - trends / opinion-2 / Parkinson's disease / Pathology / Physiological aspects / Physiology / Proteins / Smooth muscle / Translational Research, Biomedical - methods / Translational Research, Biomedical - trends / Vertebrates: nervous system and sense organs