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. 2020 Dec 10;9(12):2650. doi: 10.3390/cells9122650

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Flow diagram of relationship between HMGB1 release and BBB disruption. As described in the text, HMGB1 release is common to different kinds of injuries induced by ischemia/reperfusion, hemorrhage, trauma, and epilepsy, leading to BBB disruption through direct and indirect pathways. The peripheral inflammation caused by infection may exacerbate BBB disruption. Conversely, brain injuries may induce a vulnerability to infection in patients. BBB: blood–brain barrier; HMGB1: high mobility group box-1; iNOS: inducible nitric oxide synthase; MMPs: matrix metallo proteinases.