Abstract
Hemorrhagic stroke, mainly caused by intracerebral hemorrhage (ICH), is a severe neurological condition with high mortality and lasting disability. ICH involves bleeding into the brain parenchyma, hematoma formation, and subsequent edema and tissue damage, triggering inflammatory and degenerative responses that worsen secondary brain injury (SBI). Microglia, the brain's resident immune cells, are key mediators in this process. Their ability to sense, engulf, and clear hematoma-derived debris is essential for controlling neuroinflammation and promoting tissue repair. Central to microglial phagocytosis is lysosomal function. Lysosomes contain hydrolases - proteases, glycosidases, lipases, and nucleases - that degrade proteins, lipids, carbohydrates, and nucleic acids. This coordinated degradation ensures effective recycling of phagocytosed materials and clearance of cellular debris after hemorrhage. However, lysosomal dysfunction impairs microglial clearance capacity, leading to persistent inflammation, aggravated neuronal damage, and poor neurological recovery after ICH. This review focuses on the interplay between microglial activation, lysosomal function, and phagocytosis in hemorrhagic stroke. We examine how lysosomal impairment hinders hematoma resolution, propagates SBI, and delays functional recovery. In addition, we highlight emerging therapeutic strategies targeting the microglia-lysosome axis, such as enhancing lysosomal biogenesis and enzyme activity, as promising approaches to boost hematoma clearance and improve outcomes. Understanding and modulating microglial lysosomal function offers novel therapeutic avenues for ICH management, aiming to mitigate secondary injury and support neurological recovery.