Pivotal role of innate myeloid cells in cerebral post-ischemic sterile inflammation

Abstract

Inflammatory responses play a multifaceted role in regulating both disability and recovery after ischemic brain injury. In the acute phase of ischemic stroke, resident microglia elicit rapid inflammatory responses by the ischemic milieu. After disruption of the blood-brain barrier, peripheral-derived neutrophils and mononuclear phagocytes infiltrate into the ischemic brain. These infiltrating myeloid cells are activated by the endogenous alarming molecules released from dying brain cells. Inflammation after ischemic stroke thus typically consists of sterile inflammation triggered by innate immunity, which exacerbates the pathologies of ischemic stroke and worsens neurological prognosis. Infiltrating immune cells sustain the post-ischemic inflammation for several days; after this period, however, these cells take on a repairing function, phagocytosing inflammatory mediators and cellular debris. This time-specific polarization of immune cells in the ischemic brain is a potential novel therapeutic target. In this review, we summarize the current understanding of the phase-dependent role of innate myeloid cells in ischemic stroke and discuss the cellular and molecular mechanisms of their inflammatory or repairing polarization from a therapeutic perspective.

<p>Plasma Interleukin-37 is Elevated in Acute Ischemic Stroke Patients and Probably Associated With 3-month Functional Prognosis </p>

“…It is well accepted that immunity and inflammation play critical roles in the pathogenesis of stroke and are implicated in the primary and secondary progression of ischemic lesions, as well as in the recovery, and overall outcome after a stroke. 6 – 10 The brain responds to ischemic injury with an acute and prolonged inflammation process triggered by both resident and peripheral innate immunity, 10 and characterized by rapid activation of resident cells, production of pro-inflammatory mediators and infiltration of different types of inflammatory cells in the ischemic area of the brain. New biomarkers in immune reaction might be of great value in predicting the prognosis of acute ischemic stroke (AIS).…”

Early increased neutrophil-to-lymphocyte ratio is associated with poor 3-month outcomes in spontaneous intracerebral hemorrhage

“…The developing systemic inflammatory response is characterized by elevated numbers and activation of inflammatory-related cells, such as neutrophils, monocytes; decreased lymphocyte counts; and the release of various inflammatory cytokines and mediators [8–10]. After local brain injury, a cascade of pro-inflammatory cytokines and chemokines, such as TNF-α and IL-1β, are released by activated microglia, epithelium, and other cells in brain [8, 11]. These mediators attract peripheral neutrophils and lymphocytes, which gradually migrate and aggregate around the hematoma within a few hours; and then release various pro-inflammatory or anti-inflammatory cytokines, for recognized examples of nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9 [12].…”

Meningeal Mast Cells as Key Effectors of Stroke Pathology

“…Monocytes follow neutrophils in parenchymal infiltration after a stroke, starting to infiltrate around 6–48 h after stroke onset and staying in the brain weeks thereafter (Lambertsen et al, 2005; Perego et al, 2011). The CCR2 + Ly6C high monocytes/macrophages are thought to be involved with the acute inflammation, thus worsening the damage, whereas CX3CR1 + Ly6C low macrophages are considered as the immune cells involved in the repair process (Garcia-Bonilla et al, 2016; Tsuyama et al, 2018). However, monocyte response after stroke is very complicated.…”