C3 and Cognitive impairment: Zhang et al. showed that the levels of proinflammatory mediators (C1q, C3a, and C3b) in serum exosomes increase with age and are associated with worsening stroke outcomes (cognitive impairment and motor deficits) through a C3aR-dependent mechanism that crosses the BBB to initiate and hyperactivate microglial phagoptosis (primary phagocytosis) [81].