title: Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation.
abstract: Intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes and is associated with high mortality and morbidity. Currently, no effective medical treatment is available to improve functional outcomes in patients with ICH. Potential therapies targeting secondary brain injury are arousing a great deal of interest in translational studies. Increasing evidence has shown that inflammation is the key contributor of ICH-induced secondary brain injury. Inflammation progresses in response to various stimuli produced after ICH. Hematoma components initiate inflammatory signaling via activation of microglia, subsequently releasing proinflammatory cytokines and chemokines to attract peripheral inflammatory infiltration. Hemoglobin (Hb), heme, and iron released after red blood cell lysis aggravate ICH-induced inflammatory injury. Danger associated molecular patterns such as high mobility group box 1 protein, released from damaged or dead cells, trigger inflammation in the late stage of ICH. Preclinical studies have identified inflammatory signaling pathways that are involved in microglial activation, leukocyte infiltration, toll-like receptor (TLR) activation, and danger associated molecular pattern regulation in ICH. Recent advances in understanding the pathogenesis of ICH-induced inflammatory injury have facilitated the identification of several novel therapeutic targets for the treatment of ICH. This review summarizes recent progress concerning the mechanisms underlying ICH-induced inflammation. We focus on the inflammatory signaling pathways involved in microglial activation and TLR signaling, and explore potential therapeutic interventions by targeting the removal of hematoma components and inhibition of TLR signaling.
authors.affiliation: Department of Neurology, Xinqiao Hospital & The Second Affiliated Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Xinqiao Hospital & The Second Affiliated Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: R
authors.initials: R
authors.lastname: Anne Stetler
authors.affiliation: Department of Neurology, Xinqiao Hospital & The Second Affiliated Hospital, The Third Military Medical University, Chongqing, China. Electronic address: yangqwmlys@hotmail.com.
authors.forename: Qing-Wu
authors.initials: QW
authors.lastname: Yang
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D057170:Translational Research, Biomedical
keywords: Hematoma resolution; Hemoglobin; Inflammation; Intracerebral hemorrhage; Microglia; Toll-like receptor