title: Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice.
abstract: BACKGROUND
  Microglia/macrophages are known to play important roles in initiating brain inflammation after spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) have been proven to play a critical part in several inflammatory diseases through regulation of both adaptive and innate immune responses. Tim-3 can be expressed by microglia/macrophages and regulates their function in the innate immune response. However, the effect of Tim-3 on inflammatory responses following ICH is unclear.
  
  
  METHODS
  In this study, we investigated Tim-3 expression, the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and brain water content in peri-hematomal brain tissue at 12 hours and at 1, 3, 5, and 7 days post-ICH in wild type (WT) ICH and Tim-3-/- ICH mice. The numbers of Tim-3 positive cells,astrocytes, neutrophils and microglia/macrophages were detected using immunofluorescence staining. Cytokines were measured by ELISA. Double immunofluorescence labeling was performed to identify the cellular source of Tim-3 expression. Mouse neurological deficit scores were assessed through animal behavior.
  
  
  RESULTS
  Expression of Tim-3 increased early in mouse peri-hematomal brain tissue after autologous blood injection, peaked at day 1, and was positively correlated with the concentrations of TNF-α, IL-1β, and brain water content. Tim-3 was predominantly expressed in microglia/macrophages. Compared with WT mice, Tim-3-/- mice had reduced ICH-induced brain inflammation with decreased TNF-α and IL-1β, cerebral edema and neurological deficit scores. Moreover, Tim-/- inhibited activation of microglia/macrophages. The number of activated microglia/macrophages in Tim-3-/- ICH mice was much lower than that in WT ICH mice.
  
  
  CONCLUSIONS
  Our findings demonstrate that Tim-3 plays an important role in brain inflammation after ICH, and may be a potential treatment target.
authors.forename: ChangJun
authors.initials: C
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Si
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, No,107 Wenhuaxi road, Jinan, Shandong 250012, PR China. liuyuguang3000@163.com.
authors.forename: YuGuang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D000072597:Hepatitis A Virus Cellular Receptor 2; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus