title: Macrophage-Inducible C-Type Lectin/Spleen Tyrosine Kinase Signaling Pathway Contributes to Neuroinflammation After Subarachnoid Hemorrhage in Rats.
abstract: OBJECTIVE
  Macrophage-inducible C-type lectin (Mincle, CLEC4E) receptor is reported involved in neuroinflammation in cerebral ischemia and traumatic brain injury. This study was designed to investigate the role of Mincle and its downstream spleen tyrosine kinase (Syk) signal pathway in early brain injury after subarachnoid hemorrhage (SAH) in a rat model.
  
  
  METHODS
  Two hundred fifteen male Sprague-Dawley rats (280-320 g) were subjected to endovascular perforation model of SAH. SAH grade, neurological score, and brain water content were measured at 24 hours after SAH. Mincle/Syk, as well as CARD9 (a member of the caspase-associated recruitment domain [CARD], involved in innate immune response), interleukin-1β,and myeloperoxidase expressions were analyzed by Western blot at 24 hours after SAH. Specific cell types that expressed Mincle were detected with double immunofluorescence staining. Mincle small interfering RNA, recombinant SAP130, and a selective Syk phosphorylation inhibitor piceatannol were used for intervention.
  
  
  RESULTS
  Brain water content increased and neurological functions decreased in rats after SAH. The expression of SAP130, Mincle, Syk, and p-Syk increased at 12 hours and peaked at 24 hours after SAH. Mincle small interfering RNA reduced interleukin-1β and infiltration of myeloperoxidase positive cells, decreased brain water content, and improved neurological functions at 24 hours after SAH. Recombinant SAP130 upregulated the expression of p-Syk and CARD9 and increased the levels of interleukin-1β and myeloperoxidase, even though it did not increase brain water content nor it deteriorated neurological function at 24 hours after SAH. Syk inhibitor piceatannol reduced brain edema at 24 hours after SAH.
  
  
  CONCLUSIONS
  Mincle/Syk is involved in early brain injury after SAH, and they may serve as new targets for therapeutic intervention.
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Yue
authors.initials: Y
authors.lastname: He
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Zhen-Ni
authors.initials: ZN
authors.lastname: Guo
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Zongduo
authors.initials: Z
authors.lastname: Guo
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Junjia
authors.initials: J
authors.lastname: Tang
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.).
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: From the Departments of Anesthesiology and Basic Sciences, Loma Linda University School of Medicine, CA (Y.H., L.X., B.L., Z-N.G., Q.H., Z.G., Junjia Tang, Y.C., Y.Z., Jiping Tang, J.H.Z.); Department of Neurosurgery, Tong-ji Hospital, Wuhan, PR China (Y.H.); Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China (L.X., J.T.); Department of Neurosurgery, Jinan General Military Hospital, Jinan, PR China (B.L.); and Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China (Y.C.). johnzhang3910@yahoo.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology*; D000072377:Syk Kinase
chemical_list: C113583:Clecsf8 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C000606898:Syk protein, rat
keywords: Mincle; Syk kinase; brain injuries; subarachnoid hemorrhage