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Frik, J. ; Merl-Pham, J. ; Plesnila, N.* ; Mattugini, N. ; Kjell, J. ; Kraska, J.* ; Gómez, R.M.* ; Hauck, S.M. ; Sirko, S. ; Götz, M.

Cross-talk between monocyte invasion and astrocyte proliferation regulates scarring in brain injury.

EMBO Rep. 19:e45294 (2018)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Scar formation after brain injury is still poorly understood. To further elucidate such processes, here, we examine the interplay between astrocyte proliferation taking place predominantly at the vascular interface and monocyte invasion. Using genetic mouse models that decrease or increase reactive astrocyte proliferation, we demonstrate inverse effects on monocyte numbers in the injury site. 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. CCR2 mice show reduced scar formation with less extracellular matrix deposition, smaller lesion site and increased neuronal coverage. Surprisingly, the GFAP scar area in these mice is also significantly decreased despite increased astrocyte proliferation. Proteomic analysis at the peak of increased astrocyte proliferation reveals a decrease in extracellular matrix synthesizing enzymes in the injury sites of CCR2 mice, highlighting how early key aspects of scar formation are initiated. Taken together, we provide novel insights into the cross-regulation of juxtavascular proliferating astrocytes and invading monocytes as a crucial mechanism of scar formation upon brain injury.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Aryl Hydrocarbon Receptor ; Astrogliosis ; Monocytes ; Scar Formation ; Sonic Hedgehog Pathway ; Traumatic Brain Injury
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Quellenangaben Volume: 19, Issue: 5, Pages: , Article Number: e45294 Supplement: ,
Publisher EMBO Press
Reviewing status Peer reviewed