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The heme-hemopexin scavenging system is active in the brain, and associates with outcome after subarachnoid hemorrhage

The heme-hemopexin scavenging system is active in the brain, and associates with outcome after subarachnoid hemorrhage
The heme-hemopexin scavenging system is active in the brain, and associates with outcome after subarachnoid hemorrhage
Background and Purpose – Long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Free heme is bound by hemopexin (Hpx) and rapidly scavenged by CD91. We hypothesized that heme scavenging in the brain would be associated with outcome after haemorrhage.

Methods - Using cerebrospinal fluid (CSF) and tissue from SAH patients and control individuals, the activity of the intracranial CD91-Hpx system was examined using enzyme-linked immunoassays, ultra-high performance liquid chromatography and immunohistochemistry.

Results - In control individuals, CSF Hpx was mainly synthesized intrathecally. After SAH, CSF Hpx was high in one-third of cases, and these patients had a higher probability of delayed cerebral ischaemia and poorer neurological outcome. The intracranial CD91-Hpx system was active after SAH since CD91 positively correlated with iron deposition in brain tissue. Heme-Hpx uptake saturated rapidly after SAH, since bound heme accumulated early in the CSF. When the blood-brain barrier was compromised following SAH, serum Hpx level was lower, suggesting heme transfer to the circulation for peripheral CD91 scavenging.

Conclusions - The CD91-heme-Hpx scavenging system is important after SAH and merits further study as a potential prognostic marker and therapeutic target.
subarachnoid hemorrhage, hemoglobin, heme, hemopexin, CD91, brain, outcome
0039-2499
872-876
Garland, Patrick
1d24a0cc-81f2-4ef1-82bd-77d2510e59d6
Durnford, Andrew J.
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Okemefuna, Azubuike I.
6d830dcf-dccf-4917-a4e9-81370cbdd9d6
Dunbar, John
890f787e-a65b-4525-b8df-5bba9d82eff4
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Galea, James
b4b41adb-980d-41f0-be40-976a6aa2dab7
Boche, Delphine
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Bulters, Diederik O.
0c95cdf0-4ef7-48d5-afae-85af33b1123f
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Garland, Patrick
1d24a0cc-81f2-4ef1-82bd-77d2510e59d6
Durnford, Andrew J.
5b49b848-cf34-4024-9399-c342d71b09b6
Okemefuna, Azubuike I.
6d830dcf-dccf-4917-a4e9-81370cbdd9d6
Dunbar, John
890f787e-a65b-4525-b8df-5bba9d82eff4
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Galea, James
b4b41adb-980d-41f0-be40-976a6aa2dab7
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Bulters, Diederik O.
0c95cdf0-4ef7-48d5-afae-85af33b1123f
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b

Garland, Patrick, Durnford, Andrew J., Okemefuna, Azubuike I., Dunbar, John, Nicoll, James A.R., Galea, James, Boche, Delphine, Bulters, Diederik O. and Galea, Ian (2016) The heme-hemopexin scavenging system is active in the brain, and associates with outcome after subarachnoid hemorrhage. Stroke, 47 (3), 872-876. (doi:10.1161/STROKEAHA.115.011956). (PMID:26768209)

Record type: Article

Abstract

Background and Purpose – Long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Free heme is bound by hemopexin (Hpx) and rapidly scavenged by CD91. We hypothesized that heme scavenging in the brain would be associated with outcome after haemorrhage.

Methods - Using cerebrospinal fluid (CSF) and tissue from SAH patients and control individuals, the activity of the intracranial CD91-Hpx system was examined using enzyme-linked immunoassays, ultra-high performance liquid chromatography and immunohistochemistry.

Results - In control individuals, CSF Hpx was mainly synthesized intrathecally. After SAH, CSF Hpx was high in one-third of cases, and these patients had a higher probability of delayed cerebral ischaemia and poorer neurological outcome. The intracranial CD91-Hpx system was active after SAH since CD91 positively correlated with iron deposition in brain tissue. Heme-Hpx uptake saturated rapidly after SAH, since bound heme accumulated early in the CSF. When the blood-brain barrier was compromised following SAH, serum Hpx level was lower, suggesting heme transfer to the circulation for peripheral CD91 scavenging.

Conclusions - The CD91-heme-Hpx scavenging system is important after SAH and merits further study as a potential prognostic marker and therapeutic target.

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Accepted/In Press date: 15 November 2015
e-pub ahead of print date: 14 January 2016
Published date: March 2016
Keywords: subarachnoid hemorrhage, hemoglobin, heme, hemopexin, CD91, brain, outcome
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 384573
URI: https://eprints.soton.ac.uk/id/eprint/384573
ISSN: 0039-2499
PURE UUID: 9aafc97b-fcb7-40a6-9b3e-df080caa84e8
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 02 Dec 2015 17:10
Last modified: 10 Dec 2019 01:49

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Contributors

Author: Patrick Garland
Author: Andrew J. Durnford
Author: Azubuike I. Okemefuna
Author: John Dunbar
Author: James Galea
Author: Delphine Boche ORCID iD
Author: Diederik O. Bulters
Author: Ian Galea ORCID iD

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