title: Red blood cell lysis and brain tissue-type transglutaminase upregulation in a hippocampal model of intracerebral hemorrhage.
abstract: Red blood cell (RBC) lysis and iron release contribute to intracerebral hemorrhage (ICH)-induced brain injury. Tissue-type transglutaminase (tTG), which has a role in neurodegeneration, is upregulated after ICH. The current study investigated the effect of RBC lysis and iron release on brain tTG levels and neuronal death in a rat model of ICH. This study had three parts: (1) Male Sprague-Dawley rats received an intrahippocampal injection of 10 μL of either packed RBCs or lysed RBCs; (2) rats had a 10 μL injection of either saline, hemoglobin or FeCl2; (3) rats received a 10 μL injection of hemoglobin and were treated with an iron chelator, deferoxamine or vehicle. All rats were killed 24 h later, and the brains were sectioned for tTG and Fluoro-Jade C staining. Lysed but not packed RBCs caused marked tTG upregulation (p<0.05) and neuronal death (p<0.05) in the ipsilateral hippocampus CA-1 region. Both hemoglobin and iron mimicked the effects of lysed RBCs, resulting in tTG expression and neuronal death (p<0.05). Hemoglobin-induced tTG upreglution and neuronal death were reduced by deferoxamine (p<0.05). These results indicate that RBC lysis and iron toxicity contribute to neurodegeneration after ICH.
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.
authors: Fan
authors: F
authors: Zhao
authors: Shuijiang
authors: S
authors: Song
authors: Wenquan
authors: W
authors: Liu
authors: Richard F
authors: RF
authors: Keep
authors: Guohua
authors: G
authors: Xi
authors: Ya
authors: Y
authors: Hua
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000473:pathology / Q000502:physiology; D007839:Functional Laterality; D006454:Hemoglobins / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007501:Iron / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013266:Stilbamidines; D011503:Transglutaminases / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D006454:Hemoglobins; D013266:Stilbamidines; D007501:Iron; D011503:Transglutaminases