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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.
Montagne A, Toga AW, Zlokovic BV. Blood-Brain Barrier Permeability and Gadolinium: Benefits and Potential Pitfalls in Research. JAMA Neurol. 2016;73(1):13–14. doi:10.1001/jamaneurol.2015.2960
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