Long-term microglial phase-specific dynamics during single vessel occlusion and recanalization

Abstract

Vascular occlusion leading to brain dysfunctions is usually considered evoking microglia-induced inflammation response. However, it remains unclear how microglia interact with blood vessels in the development of vascular occlusion-related brain disorders. Here, we illuminate long-term spatiotemporal dynamics of microglia during single vessel occlusion and recanalization. Microglia display remarkable response characteristics in different phases, including acute reaction, rapid diffusion, transition and chronic effect. Fibrinogen-induced microglial cluster promotes major histocompatibility complex II (MHCII) expression. Microglial soma represents a unique filament-shape migration and has slower motility compared to the immediate reaction of processes to occlusion. We capture proliferative microglia redistribute territory. Microglial cluster resolves gradually and microglia recover to resting state both in the morphology and function in the chronic effect phase. Therefore, our study offers a comprehensive analysis of spatiotemporal dynamics of microglia and potential mechanisms to both vessel occlusion and recanalization. Microglial phase-specific response suggests the morphological feature-oriented phased intervention would be an attractive option for vascular occlusion-related diseases treatments.

Macrophage and monocyte subsets in response to ischemic stroke

“…Interestingly, the so-called repair-associated microglia were recently described in a cerebrovascular injury model as microglia with proangiogenic properties, expressing high levels of VEGF and concomitant physiological microglial levels of P2RY12 and CX3CR1 [34]. Using the laser ablation technique for single vessel occlusion, Xie et al demonstrated that retraction and elongation of microglial processes in the first hours, as a rapid response and slower migration of cell somata toward the occlusion site, were temporally dependent on the spatial distance of microglia from the occluded vessel [35]. In a model of permanent middle cerebral artery occlusion (MCAo), amoeboid microglia were shown to be present in the border area of the infarct lesion as early as 30 minutes after occlusion (Fig.…”

“…Using the laser ablation technique for single vessel occlusion, Xie et al. demonstrated that retraction and elongation of microglial processes in the first hours, as a rapid response and slower migration of cell somata toward the occlusion site, were temporally dependent on the spatial distance of microglia from the occluded vessel [35]. In a model of permanent middle cerebral artery occlusion (MCAo), amoeboid microglia were shown to be present in the border area of the infarct lesion as early as 30 minutes after occlusion (Fig.…”