The immune regulation of complement system in intracerebral hemorrhage(ICH): the double-edged effects of mechanisms and therapeutic strategies.

The complement system plays a dual role in the immunopathophysiological process following intracerebral hemorrhage. Its excessive activation during the acute phase can exacerbate neuroinflammation, disrupt the blood-brain barrier integrity, recruit destructive immune cells, and directly induce cell lysis, thereby worsening secondary brain injury. However, during the subacute and chronic phases, the complement system shows repair potential, including promoting hematoma clearance via pathways such as C3b-CR3, regulating inflammation resolution, and possibly participating in neural remodeling. This review systematically outlines how the complement system regulates immune responses at different stages after intracerebral hemorrhage by affecting the blood-brain barrier, interacting with various immune cells (microglia/macrophages, neutrophils, astrocytes, lymphocytes), modulating cytokine networks, and mediating phagocytosis and cell death. Based on its dual spatiotemporal characteristics of "damage and repair," future therapeutic strategies should focus on precise interventions: selectively inhibiting the destructive complement pathways (such as C5a/C3a and the membrane attack complex) during the acute phase, while preserving or enhancing its protective functions (such as opsonization and phagocytosis) during the recovery phase. This stage-specific complement-targeted regulation provides new theoretical support and therapeutic ideas for improving the prognosis of intracerebral hemorrhage.