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Viewpoint |

Blood-Brain Barrier Permeability and Gadolinium Benefits and Potential Pitfalls in Research

Axel Montagne, PhD1; Arthur W. Toga, PhD2; Berislav V. Zlokovic, MD, PhD1
[+] Author Affiliations
1Zilkha Neurogenetic Institute, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles
2Institute for Neuroimaging and Informatics, Department of Neurology, University of Southern California, Los Angeles
JAMA Neurol. 2016;73(1):13-14. doi:10.1001/jamaneurol.2015.2960.
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This Viewpoint discusses the benefits and risks of gadolinium-based contrast agents used in magnetic resonance imaging in relation to blood-brain barrier permeability.

The blood-brain barrier (BBB) normally prevents blood-derived products, pathogens, and cells from entering the brain.1 The BBB is disrupted in multiple neurological disorders, resulting in entry and accumulation in neurons and the neuronal interstitium of several toxic molecules from blood. These include fibrinogen, thrombin, hemoglobin, iron-containing hemosiderin, free iron, plasmin (an extracellular matrix-degrading enzyme), environmental toxins and metals, and possibly microbial pathogens, which can have direct neuronal toxic effects and lead to oxidant stress, activation of proinflammatory microglia response, or disruption of neuronal matrix causing neuronal injury, neurodegenerative changes, and neuronal loss.1 Additionally, the BBB breakdown leads to loss of the brain’s immune privilege, which may result in the formation of autoantibodies against different neuronal cell membrane proteins and axonal proteins.

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