Microglia-derived interleukin-10 accelerates post-intracerebral hemorrhage hematoma clearance by regulating CD36.

Hematoma size after intracerebral hemorrhage (ICH) significantly affects patient outcome. However, our knowledge of endogenous mechanisms that underlie hematoma clearance and the potential role of the anti-inflammatory cytokine interleukin-10 (IL-10) is limited. Using organotypic hippocampal slice cultures and a collagenase-induced ICH mouse model, we investigated the role of microglial IL-10 in phagocytosis ex vivo and hematoma clearance in vivo. In slice culture, exposure to hemoglobin induced IL-10 expression in microglia and enhanced phagocytosis that depended on IL-10-regulated expression of CD36. Following ICH, IL-10-deficient mice had more severe neuroinflammation, brain edema, iron deposition, and neurologic deficits associated with delayed hematoma clearance. Intranasal administration of recombinant IL-10 accelerated hematoma clearance and improved neurologic function. Additionally, IL-10-deficient mice had weakened in vivo phagocytic ability owing to decreased expression of microglial CD36. Moreover, loss of IL-10 significantly increased monocyte-derived macrophage infiltration and enhanced brain inflammation in vivo. These results indicate that IL-10 regulates microglial phagocytosis and monocyte-derived macrophage infiltration after ICH and that CD36 is a key phagocytosis effector regulated by IL-10. Leveraging the innate immune response to ICH by augmenting IL-10 signaling may provide a useful strategy for accelerating hematoma clearance and improving neurologic outcome in clinical translation studies.

Corrigendum: Ultrastructural characteristics of neuronal death and white matter injury in mouse brain tissues after intracerebral hemorrhage: coexistence of ferroptosis, autophagy, and necrosis.

[This corrects the article DOI: 10.3389/fneur.2018.00581.].

Ferroptosis and Its Role in Diverse Brain Diseases.

Ferroptosis is a recently identified, iron-regulated, non-apoptotic form of cell death. It is characterized by cellular accumulation of lipid reactive oxygen species that ultimately leads to oxidative stress and cell death. Although first identified in cancer cells, ferroptosis has been shown to have significant implications in several neurologic diseases, such as ischemic and hemorrhagic stroke, Alzheimer's disease, and Parkinson's disease. This review summarizes current research on ferroptosis, its underlying mechanisms, and its role in the progression of different neurologic diseases. Understanding the role of ferroptosis could provide valuable information regarding treatment and prevention of these devastating diseases.

Ultrastructural Characteristics of Neuronal Death and White Matter Injury in Mouse Brain Tissues After Intracerebral Hemorrhage: Coexistence of Ferroptosis, Autophagy, and Necrosis.

Although intracerebral hemorrhage (ICH) is a devastating disease worldwide, the pathologic changes in ultrastructure during the acute and chronic phases of ICH are poorly described. In this study, transmission electron microscopy was used to examine the ultrastructure of ICH-induced pathology. ICH was induced in mice by an intrastriatal injection of collagenase. Pathologic changes were observed in the acute (3 days), subacute (6 days), and chronic (28 days) phases. Compared with sham animals, we observed various types of cell death in the injured striatum during the acute phase of ICH, including necrosis, ferroptosis, and autophagy. Different degrees of axon degeneration in the striatum were seen in the acute phase, and axonal demyelination was observed in the ipsilateral striatum and corpus callosum at late time points. In addition, phagocytes, resident microglia, and infiltrating monocyte-macrophages were present around red blood cells and degenerating neurons and were observed to engulf red blood cells and other debris. Many synapses appeared abnormal or were lost. This systematic analysis of the pathologic changes in ultrastructure after ICH in mice provides information that will be valuable for future ICH pathology studies.