title: Role of Lipocalin-2 in Thrombin-Induced Brain Injury.
abstract: OBJECTIVE
  Thrombin and lipocalin-2 (LCN2) contribute to intracerebral hemorrhage-induced brain injury. Thrombin-induced brain damage is partially through a thrombin receptor, protease-activated receptor-1. LCN2 is involved in cellular iron transport and neuroinflammation. This study investigated the role of LCN2 in thrombin-induced brain injury.
  
  
  METHODS
  There were 3 parts in this study. First, male adult C57BL/6 wild-type or LCN2 knockout (LCN2 KO) mice had an intracaudate injection of thrombin (0.4 U) or saline. Second, LCN2 KO mice had an injection of thrombin (0.4 U) with recombinant mouse LCN2 protein (1 μg) into the right caudate. Third, protease-activated receptor-1 KO or wild-type mice had an intracaudate injection of thrombin or saline. All mice had T2-weighted magnetic resonance imaging and behavioral tests. Brains were used for histology, immunohistochemistry, and Western blotting.
  
  
  RESULTS
  Intracerebral thrombin injection caused LCN2 upregulation and brain injury in mice. Thrombin-induced brain swelling, blood-brain barrier disruption, neuronal death, and neurological deficits were markedly less in LCN2 KO mice (P<0.05) and were exacerbated by exogenous LCN2 coinjection. In addition, thrombin injection resulted in less LCN2 expression and brain injury in protease-activated receptor-1 KO mice.
  
  
  CONCLUSIONS
  Thrombin upregulates LCN2 through protease-activated receptor-1 activation and causes brain damage.
authors: From the Department of Neurosurgery, University of Michigan, Ann Arbor.
authors: Shanshan
authors: S
authors: Mao
authors: From the Department of Neurosurgery, University of Michigan, Ann Arbor.
authors: Guohua
authors: G
authors: Xi
authors: From the Department of Neurosurgery, University of Michigan, Ann Arbor.
authors: Richard F
authors: RF
authors: Keep
authors: From the Department of Neurosurgery, University of Michigan, Ann Arbor. yahua@umich.edu.
authors: Ya
authors: Y
authors: Hua
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000378:metabolism; D013917:Thrombin; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D044463:Receptor, PAR-1; C071332:Lcn2 protein, mouse; D013917:Thrombin
keywords: brain edema; lipocalin 2 protein, mouse; magnetic resonance imaging; protease-activated receptor 1; thrombin