title: Neuroprotective role of haptoglobin after intracerebral hemorrhage.
abstract: After intracerebral hemorrhage (ICH), the brain parenchyma is exposed to blood containing red blood cells (RBCs) and consequently to its lysis products. Iron-rich hemoglobin (Hb) is the most abundant protein in RBCs. When released into the brain parenchyma during hemolysis, Hb becomes a central mediator of cytotoxicity. Our study indicates that haptoglobin (Hp), an acute-phase response protein primarily synthesized in the liver and known to bind and neutralize Hb in the bloodstream, is also expressed in brain in which it plays an important role in defending neurons from damage induced by hemolytic products after ICH. We demonstrate that the Hb-induced hypohaptoglobinemia aggravates ICH-induced brain damage while pharmacologic intervention with sulforaphane to induce brain Hp is linked to a reduction in brain damage. In agreement with these findings, Hp deficiency worsens whereas Hp overexpression alleviates ICH-mediated brain injury. We also identified that oligodendroglia are the primary source of brain-derived Hp among brain cells and that oligodendroglia-released Hp plays protective roles against Hb-mediated toxicity to neurons and oligodendrocytes. We conclude that Hp, particularly the brain-derived Hp, plays cytoprotective roles and represents a potential therapeutic target for ICH treatment.
authors.affiliation: Stroke Program, Department of Neurology, University of Texas Health Science Center, Medical School at Houston, Houston, Texas 77030, USA.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Zhao
authors.forename: Shen
authors.initials: S
authors.lastname: Song
authors.forename: Guanghua
authors.initials: G
authors.lastname: Sun
authors.forename: Roger
authors.initials: R
authors.lastname: Strong
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: James C
authors.initials: JC
authors.lastname: Grotta
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Aronowski
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D018920:Coculture Techniques; D005260:Female; D006242:Haptoglobins / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018696:Neuroprotective Agents; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D006242:Haptoglobins; D018696:Neuroprotective Agents