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Transcellular blood-brain barrier disruption in malaria-induced reversible brain edema

Brain swelling occurs in cerebral malaria (CM) and may either reverse or result in fatal outcome. It is currently unknown how brain swelling in CM reverses, as brain swelling at the acute stage is difficult to study in humans and animal models with reliable induction of reversible edema are not know...

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Main Authors: Jin, Jessica (Author) , Ba, Mame Aida (Author) , Wai, Chi Ho (Author) , Mohanty, Sanjib (Author) , Sahu, Praveen K. (Author) , Pattnaik, Rajyabardhan (Author) , Pirpamer, Lukas (Author) , Fischer, Manuel (Author) , Heiland, Sabine (Author) , Lanzer, Michael (Author) , Frischknecht, Friedrich (Author) , Müller, Ann-Kristin (Author) , Pfeil, Johannes (Author) , Majhi, Megharay (Author) , Cyrklaff, Marek (Author) , Wassmer, Samuel C. (Author) , Bendszus, Martin (Author) , Hoffmann, Angelika (Author)
Format: Article (Journal)
Language:English
Published: 8 March 2022
In: Life science alliance
Year: 2022, Volume: 5, Issue: 6, Pages: 1-11
ISSN:2575-1077
DOI:10.26508/lsa.202201402
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.26508/lsa.202201402
Verlag, lizenzpflichtig, Volltext: https://www.life-science-alliance.org/content/5/6/e202201402
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Author Notes:Jessica Jin, Mame Aida Ba, Chi Ho Wai, Sanjib Mohanty, Praveen K. Sahu, Rajyabardhan Pattnaik, Lukas Pirpamer, Manuel Fischer, Sabine Heiland, Michael Lanzer, Friedrich Frischknecht, Ann-Kristin Mueller, Johannes Pfeil, Megharay Majhi, Marek Cyrklaff, Samuel C. Wassmer, Martin Bendszus, Angelika Hoffmann
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Summary:Brain swelling occurs in cerebral malaria (CM) and may either reverse or result in fatal outcome. It is currently unknown how brain swelling in CM reverses, as brain swelling at the acute stage is difficult to study in humans and animal models with reliable induction of reversible edema are not known. In this study, we show that reversible brain swelling in experimental murine CM can be induced reliably after single vaccination with radiation-attenuated sporozoites as proven by in vivo high-field magnetic resonance imaging. Our results provide evidence that brain swelling results from transcellular blood-brain barrier disruption (BBBD), as revealed by electron microscopy. This mechanism enables reversal of brain swelling but does not prevent persistent focal brain damage, evidenced by microhemorrhages, in areas of most severe BBBD. In adult CM patients magnetic resonance imaging demonstrate microhemorrhages in more than one third of patients with reversible edema, emphasizing similarities of the experimental model and human disease. Our data suggest that targeting transcellular BBBD may represent a promising adjunct therapeutic approach to reduce edema and may improve neurological outcome.
Item Description:Gesehen am 19.05.2022
Physical Description:Online Resource
ISSN:2575-1077
DOI:10.26508/lsa.202201402

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