title: Cytoprotective role of haptoglobin in brain after experimental intracerebral hemorrhage.
abstract: After intracerebral hemorrhage (ICH), hemoglobin (Hb) that is released from erythrocytes within the brain hematoma is highly cytotoxic and leads to severe brain edema and direct neuronal damage. Therefore, neutralization of Hb could represent an important target for reducing the secondary injury after ICH. Haptoglobin (Hp), an endogenous Hb-binding protein in blood plasma, is found in this study to be upregulated in the hematoma-affected brain after ICH. Both in vivo and in vitro studies indicate that Hp upregulation is primarily mediated by oligodendrocytes. Hp acts as a secretory protein capable of neutralizing the cell-free Hb. We also found in an "ICH-like" injury that Hp-KO mice show the most severe brain injury and neurological deficits, whereas Hp-Tg mice are the most resistant to ICH injury, suggesting that a higher Hp level is associated with the increased resistance of animals to hemolytic product-mediated brain injury after ICH. We conclude that brain-derived Hp plays a cytoprotective role after ICH, and Hp may represent a new potential therapeutic target for management of ICH.
authors: Stroke Program-Department of Neurology, University of Texas Health Science Center, Medical School at Houston, Houston, TX 77030, USA.
authors: Xiurong
authors: X
authors: Zhao
authors: Shen
authors: S
authors: Song
authors: Guanghua
authors: G
authors: Sun
authors: Jie
authors: J
authors: Zhang
authors: Roger
authors: R
authors: Strong
authors: Lihua
authors: L
authors: Zhang
authors: James C
authors: JC
authors: Grotta
authors: Jaroslaw
authors: J
authors: Aronowski
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000473:pathology; D019610:Cytoprotection; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000502:physiology; D006242:Haptoglobins / Q000172:deficiency / Q000378:metabolism / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009460:Neurologic Examination; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006242:Haptoglobins; D004676:Myelin Basic Protein; D007770:L-Lactate Dehydrogenase