PT  - JOURNAL ARTICLE
AU  - A Mohamud Yusuf
AU  - N Hagemann
AU  - X Zhang
AU  - M Zafar
AU  - T Hussner
AU  - C Bromkamp
AU  - C Martiny
AU  - T Tertel
AU  - V Börger
AU  - F Schumacher
AU  - FA Solari
AU  - M Hasenberg
AU  - C Kleinschnitz
AU  - TR Doeppner
AU  - B Kleuser
AU  - A Sickmann
AU  - M Gunzer
AU  - B Giebel
AU  - R Kolesnick
AU  - E Gulbins
AU  - DM Hermann
TI  - Acid sphingomyelinase deactivation post-ischemia/ reperfusion promotes cerebral angiogenesis and brain remodeling via small extracellular vesicles
AID  - 10.1101/2021.03.01.433387
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.01.433387
4099  - http://biorxiv.org/content/early/2021/03/02/2021.03.01.433387.short
4100  - http://biorxiv.org/content/early/2021/03/02/2021.03.01.433387.full
AB  - Functional inhibitors of acid sphingomyelinase are clinically used as anti-depressants since ∼60 years. Here, we show that acid sphingomyelinase inhibition by the antidepressants amitriptyline, fluoxetine and desipramine protects from ischemia/reperfusion and elicits a profound brain remodeling response with increased angiogenesis, improved blood-brain barrier integrity, reduced brain leukocyte infiltration and increased neuronal survival. Angiogenesis is promoted by small extracellular vesicles with bona fide characteristics of exosomes, which are released from endothelial cells and which constitute an elegant target for the amplification of stroke recovery.Competing Interest StatementThe authors have declared no competing interest.