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A TSPO ligand attenuates brain injury after intracerebral hemorrhage
Author(s) -
Li Minshu,
Ren Honglei,
Sheth Kevin N.,
Shi FuDong,
Liu Qiang
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601377rr
Subject(s) - translocator protein , microglia , neuroprotection , intracerebral hemorrhage , pharmacology , inflammation , collagenase , neuroinflammation , medicine , blood–brain barrier , infiltration (hvac) , striatum , central nervous system , chemistry , immunology , biochemistry , materials science , subarachnoid hemorrhage , composite material , dopamine , enzyme
Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. After ICH, the immediate infiltration of leukocytes and activation of microglia are accompanied by a rapid up‐regulation of the 18‐kDa translocator protein (TSPO). TSPO ligands have shown anti‐inflammatory and neuroprotective properties in models of CNS injury. In this study, we determined the impact of a TSPO ligand, etifoxine, on brain injury and inflammation in 2 mouse models of ICH. TSPO was up‐regulated in Iba1 + cells from brains of patients with ICH and in CD11b + CD45 int cells from mice subjected to collagenase‐induced ICH. Etifoxine significantly reduced neurodeficits and perihematomal brain edema after ICH induction by injection of either autologous blood or collagenase. In collagenase‐induced ICH mice, the protection of etifoxine was associated with reduced leukocyte infiltration into the brain and microglial production of IL‐6 and TNF‐α. Etifoxine improved blood–brain barrier integrity and diminished cell death. Notably, the protective effect of etifoxine was abolished in mice depleted of microglia by using a colony‐stimulating factor 1 receptor inhibitor. These results indicate that the TSPO ligand etifoxine attenuates brain injury and inflammation after ICH. TSPO may be a viable therapeutic target that requires further investigations in ICH.—Li, M., Ren, H., Sheth, K. N., Shi, F.‐D., Liu, Q. A TSPO ligand attenuates brain injury after intracerebral hemorrhage. FASEB J . 31, 3278–3287 (2017). www.fasebj.org