Fibrinogen regulates lesion border‐forming reactive astrocyte properties after vascular damage

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Abstract: Reactive astrocytes at the border of damaged neuronal tissue organize into a barrier surrounding the fibrotic lesion core, separating this central region of inflammation and fibrosis from healthy tissue. Astrocytes are essential to form the border and for wound repair but interfere with neuronal regeneration. However, the mechanisms driving these astrocytes during central nervous system (CNS) disease are unknown. Here we show that blood-derived fibrinogen is enriched at the interface of lesion border-forming elongated astrocytes after cortical brain injury. Anticoagulant treatment depleting fibrinogen reduces astrocyte reactivity, extracellular matrix deposition and inflammation with no change in the spread of inflammation, whereas inhibiting fibrinogen conversion into fibrin did not significantly alter astrocyte reactivity, but changed the deposition of astrocyte extracellular matrix. RNA sequencing of fluorescence-activated cell sorting-isolated astrocytes of fibrinogen-depleted mice after cortical injury revealed repressed gene expression signatures associated with astrocyte reactivity, extracellular matrix deposition and immune-response regulation, as well as increased gene expression signatures associated with astrocyte metabolism and astrocyte-neuron communication. Systemic pharmacologic depletion of fibrinogen resulted in the absence of elongated, border-forming astrocytes and increased the survival of neurons in the lesion core after cortical injury. These results identify fibrinogen as a critical trigger for lesion border-forming astrocyte properties in CNS disease

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: Glia. - 70, 7 (2022) , 1251-1266, ISSN: 1098-1136

Classification: Medizin, Gesundheit

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2022

Creator: Conforti, Pasquale
Mezey, Szilvia
Nath, Suvra
Chu, Yu-Hsuan
Malik, Subash C.
Martínez Santamaría, Jose C.
Deshpande, Sachin S.
Pous, Lauriane
Zieger, Barbara
Schachtrup, Christian

DOI: 10.1002/glia.24166

URN: urn:nbn:de:bsz:25-freidok-2254750

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:20 AM CEST

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2022

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Fibrinogen regulates lesion border‐forming reactive astrocyte properties after vascular damage

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Other Objects (12)

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