Intracerebral hemorrhage (ICH) is a significant global disease with high mortality and morbidity. Despite advances in clinical and preclinical research, the prognosis of ICH remains poor due to the complex pathological process. This study aimed to understand better the cellular and molecular processes that occur in mouse ICH. We conducted single-cell resolution spatial transcriptomic analysis of brain tissues at 1, 3, 7, 14, and 28 days after ICH. We identified critical transcription factors governing the dynamic pathological responses post-ICH. Our investigation revealed the dynamic pathological progression following ICH, with a particular emphasis on pivotal transcription factors governing these processes. Notably, oOn the seventh day, active phagocytosis, iron metabolism, and lipid processing were observed at the lesion core, while genes associated with neural repair were detected at the lesion border. Furthermore, we uncovered 18 cell subtypes related to ICH and mapped their spatiotemporal distribution within the lesion. Remarkably, even at the 14-day mark, lipid accumulation persisted within the lesion, leading to foam cells formation and chronic inflammation. B cells may also be activated by excess lipids and produce antibodies that neutralize oxidized low-density lipoprotein. By dissecting the intricate communication network among these subtypes, we revealed a dynamic interplay between pro-inflammatory and anti-inflammatory signaling and the coexistence between neural regenerative and inhibitory signals. In conclusion, this study provides a spatiotemporal molecular atlas of mouse brain hemorrhage that lays the groundwork for future therapeutic strategies.
