The Role of Complement C3a Receptor in Stroke

Neuromolecular Med. 2019 Dec;21(4):467-473. doi: 10.1007/s12017-019-08545-7. Epub 2019 May 17.


The complement system is a key regulator of the innate immune response against diseased tissue that functions across multiple organ systems. Dysregulation of complement contributes to the pathogenesis of a number of neurological diseases including stroke. The C3a anaphylatoxin, via its cognate C3a receptor (C3aR), mediates inflammation by promoting breakdown of the blood-brain barrier and the massive infiltration of leukocytes into ischemic brain in experimental stroke models. Studies utilizing complement deficient mice as well as pharmacologic C3aR antagonists have shown a reduction in tissue injury and mortality in murine stroke models. The development of tissue-specific C3aR knockout mice and more specific C3aR antagonists is warranted to facilitate our understanding of the role of the C3aR in brain ischemia with the ultimate goal of clinical translation of therapies targeting C3aR in stroke patients.

Keywords: C3a receptor; C3a receptor antagonist; Central nervous system; Complement cascade; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / therapeutic use
  • Benzhydryl Compounds / therapeutic use
  • Blood-Brain Barrier
  • Complement Activation
  • Complement C3a / physiology*
  • Complement Inactivating Agents / therapeutic use
  • Disease Models, Animal
  • Humans
  • Immunity, Innate
  • Mice
  • Mice, Knockout
  • Neuroimmunomodulation*
  • Neuroprotective Agents / therapeutic use
  • Receptors, Complement / antagonists & inhibitors
  • Receptors, Complement / deficiency
  • Receptors, Complement / physiology*
  • Stroke / drug therapy
  • Stroke / epidemiology
  • Stroke / immunology*
  • Stroke / physiopathology
  • Translational Research, Biomedical


  • Benzhydryl Compounds
  • Complement Inactivating Agents
  • Neuroprotective Agents
  • Receptors, Complement
  • SB 290157
  • complement C3a receptor
  • Complement C3a
  • Arginine