Profiling endogenous and recruited brain macrophages following acute stroke

Introduction

Following acute ischemic stroke (AIS), a cascade of acute and chronic neuroinflammatory events occur at both local and distal regions - a response driven by endogenous and recruited brain macrophages. Prior studies depicting the long-term consequences of AIS have demonstrated enhanced rates of both neurodegenerative and neuropsychiatric disorders – thought to be driven by distal macrophage activity.  However, little is known about the temporal and spatial distributions of brain macrophage populations post-AIS, with such knowledge vital to identify treatment targets.

Methods

 In this murine-based study, we initially employed the use of flow cytometry and single-cell RNA sequencing to characterize changes in monocyte, monocyte-derived cells (MDCs), and microglial landscapes. Subsequently, the study employed immunohistochemistry to localise Iba1 (macrophage marker) and Ki67 (a marker of proliferation) within the tissue 3- and 7-days post-stroke. Finally, we employed the use of a novel fate-mapping model, we preliminarily differentiated between the distributions of each macrophage population at day-3 post-stroke

Results

Our results demonstrating that both microglia and MDCs increase in cell count following AIS. Whilst microglia undergo proliferation, the increase in MDCs is secondary to enhanced monocyte infiltration and differentiation only. Latterly, we demonstrated macrophage accumulation at both the infarct and tracts connected to the ischaemic region, thus highlighting the locations vulnerable to the global effects following AIS. Finaly, through the use of the fate-mapping model, we demonstrated that microglia are located both at the infarct and connected tracts, with MDMs restricted to the site of the infarct only.

Conclusion

As such, these findings advocate for future studies to experimental target microglia during the chronic phase of AIS, and subsequently develop therapeutics, to enhance patient outcomes and reduce healthcare burdens.

To be updated shortly..