IBBM   21076
INSTITUTO DE BIOTECNOLOGIA Y BIOLOGIA MOLECULAR
Unidad Ejecutora - UE
artículos
Título:
A cross-talk between invading monocytes and reactive astrocyte proliferation determines scar formation after traumatic brain injury
Autor/es:
PLESNILA N; HAUCK SM; FRIK J; MATTUGINI N; SIRKO S; MERL-PHAM J; RICARDO M GOMEZ; GOTZ M
Revista:
EMBO REPORTS
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Lugar: Londres; Año: 2018 vol. e452 p. 1 - 20
ISSN:
1469-221X
Resumen:
When and how scar formation is determined after mammalian brain injury, is not yet understood. Here we explored the role of proliferating astrocytes that are predominantly located in direct vicinity to the blood vessels after traumatic and ischemic brain injury. We use genetic mouse models showing that decreased astrocyte proliferation increases monocytes in the injury site, while increasing astrocyte proliferation reduces their number. Conversely, reducing monocyte invasion using CCR2-/- mice causes a strong increase in astrocyte proliferation, demonstrating an intriguing negative cross-regulation between these cell types at the vascular interface. Importantly, CCR2-/- mice showed much less scar formation with much reduced extracellular matrix deposition and lesion site while neuronal coverage was increased. Surprisingly, also the GFAP+ scar area was significantly decreased despite increased astrocyte proliferation. Proteomic analysis at the peak of increased astrocyte proliferation revealed a decrease in ECM synthesizing enzymes already at this early stage, highlighting that key aspects of scar formation are initiated at this early time point. Moreover, we show that juxtavascular astrocytes have higher levels of aryl hydrocarbon receptor compared to other astrocytes providing a link to their reduction of monocyte recruitment given the role of this pathway in Ccl2 down-regulation. Taken together we provide key novel insights into the corss-regulation of juxtavascular proliferating astrocytes and invading monocytes as a key mechanism of scar formation upon brain injury.