Cellular and molecular mechanisms of sterile inflammation in ischemic stroke.

Cerebral inflammation is a promising therapeutic target for ischemic stroke. After ischemic stroke, inflammatogenic self molecules, which originate from damaged brain tissue due to ischemia, activate infiltrating immune cells (neutrophils, macrophages, and lymphocytes) and thereby trigger sterile inflammation. Innate immunity plays the central role in sterile inflammation at the acute phase of brain ischemia, although immune response by T lymphocytes (innate or acquired immunity) is also implicated in inflammation at the subacute phase, which sustains ischemic brain damage. In the recovery phase, infiltrating macrophages remove the damage-associated molecular patterns (DAMPs) from the ischemic brain. These pro-resolving myeloid cells also produce neurotrophic factors involved in neural repair. Through a series of inflammatory mechanisms activated by ischemic stroke, various immune cells change their functions from inflammation to repair in a precise process. In order to establish therapeutic strategies for the improvement of neurological deficits after ischemic stroke, it is necessary to clarify the detailed molecular and cellular mechanisms of sterile inflammation after ischemic brain injury.