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

ABSTRACT: Scar formation after brain injury is still ill understood. Here we examined the interplay between astrocyte proliferation and monocyte invasion. Using genetic mouse models to decrease or increase reactive astrocyte proliferation, we demonstrate inverse effects on monocyte numbers in the injury site, with e.g. reduced monocyte numbers when astrocyte proliferation was increased. 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 showed reduced scar formation with less extracellular matrix deposition, smaller lesion site and increased neuronal coverage. 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 in the injury sites of CCR2-/- mice already at this stage, highlighting how early key aspects of scar formation are initiated. Taken together we provide key novel insights into the cross-regulation of juxtavascular proliferating astrocytes and invading monocytes as a key mechanism of scar formation upon brain injury.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Juliane Merl-Pham  

LAB HEAD: Magdalena Götz

PROVIDER: PXD008906 | Pride | 2018-04-16

REPOSITORIES: pride