PROJECT: JTC2022 - Cerebrovascular: MICROBLEEDs

Cerebral small-vessel disease (CSVD), are a major cause of frailty and cognitive impairment. A characteristic hallmark of CSVD are cerebral microbleeds (CMBs), which are spontaneous hemorrhages within the cerebral white or gray matter, triggered by small vessel ruptures for example induced by chronic hypertension or BBB dysfunction. Although CMBs are very common in the elderly population (20-30%), the pathways leading to neuronal death are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2), has emerged as a key signaling receptor on microglia, the primary immune cells in the CNS, as well as peripheral macrophages and dendritic cells, and has been shown to critically contribute to ischemic cell damage. Hence, we propose to investigate the role of TREM2 in CMBs and its impact on other cell populations including astrocytes, pericytes, perivascular fibroblasts and neurons. CMBs will be performed in a standardized experimental setup across all partners, enabling us to generate a landscape of acute and long-term multicellular damage responses and resulting neuronal network changes. Longitudinal 2-Photon in vivo imaging of specific cell populations will be conducted to track ongoing changes to cell function and network changes. Spatial spatial mass cytometry imaging approach to interconnect the expression pattern changes in relation to the CBMs and the other cell types in mouse and human tissue samples to validate our findings.