Heme-Hemopexin Scavenging Is Active in the Brain and Associates With Outcome After Subarachnoid Hemorrhage

Stroke; a Journal of Cerebral Circulation
Patrick GarlandIan Galea

Abstract

Long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Free heme is bound by hemopexin and rapidly scavenged by CD91. We hypothesized that heme scavenging in the brain would be associated with outcome after hemorrhage. Using cerebrospinal fluid and tissue from patients with SAH and control individuals, the activity of the intracranial CD91-hemopexin system was examined using ELISA, ultrahigh performance liquid chromatography, and immunohistochemistry. In control individuals, cerebrospinal fluid hemopexin was mainly synthesized intrathecally. After SAH, cerebrospinal fluid hemopexin was high in one third of cases, and these patients had a higher probability of delayed cerebral ischemia and poorer neurological outcome. The intracranial CD91-hemopexin system was active after SAH because CD91 positively correlated with iron deposition in brain tissue. Heme-hemopexin uptake saturated rapidly after SAH because bound heme accumulated early in the cerebrospinal fluid. When the blood-brain barrier was compromised after SAH, serum hemopexin level was lower, suggesting heme transfer to the circulation for peripheral CD91 scavenging. The CD91-heme-hemopexin scavenging system is important after SAH an...Continue Reading

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Citations

Jul 22, 2018·Journal of Neurosurgery·Ajith J ThomasKhalid A Hanafy
Jan 20, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·D Andrew WilkinsonGuohua Xi
May 14, 2020·Stroke; a Journal of Cerebral Circulation·Kelly B MahaneyJennifer M Strahle
Jun 22, 2018·Nature Reviews. Neurology·Diederik BultersIan Galea
Nov 30, 2016·Translational Stroke Research·Dewei GuoYa Hua
Nov 20, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jenna L LeclercSylvain Doré
Jun 19, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Gaiqing WangJiping Tang
Sep 30, 2017·Stroke and Vascular Neurology·Thomas GartonGuohua Xi
Jun 10, 2017·The Journal of Biological Chemistry·Peter HahlAnn Smith
Apr 30, 2020·Brain Communications·Patrick GarlandIan Galea
Dec 27, 2017·Journal of Cellular and Molecular Medicine·Gaiqing WangJiping Tang
Mar 27, 2019·Annals of Clinical and Translational Neurology·Nicci CampbellIan Galea
Aug 14, 2019·Frontiers in Immunology·Ghee Rye LeeLeo E Otterbein
Aug 1, 2020·Frontiers in Neuroscience·Pengjie PanJiang Wu
Oct 4, 2019·CNS Neuroscience & Therapeutics·Yi-Bin JiangRong Hu
Jun 24, 2020·Nature Communications·Jinman ChenYongjun Wang
Oct 17, 2019·Molecular Neurobiology·Steven A RobicsekSylvain Doré
Apr 14, 2018·American Journal of Respiratory Cell and Molecular Biology·Olga RafikovaRuslan Rafikov
Apr 9, 2021·Stroke; a Journal of Cerebral Circulation·Luiz Ricardo C VasconcellosPedro Moreno Pimentel-Coelho
Jul 3, 2021·International Journal of Molecular Sciences·Rezan Ashayeri AhmadabadMaryam Khaleghi Ghadiri

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