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
872-876
Garland, Patrick
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Durnford, Andrew J.
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Okemefuna, Azubuike I.
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Dunbar, John
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Nicoll, James A.R.
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Galea, James
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Boche, Delphine
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Bulters, Diederik O.
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Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
March 2016
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.
d6f9644a-a32f-45d8-b5ed-be54486ec21d
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), .
(doi:10.1161/STROKEAHA.115.011956).
(PMID:26768209)
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: http://eprints.soton.ac.uk/id/eprint/384573
ISSN: 0039-2499
PURE UUID: 9aafc97b-fcb7-40a6-9b3e-df080caa84e8
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Date deposited: 02 Dec 2015 17:10
Last modified: 15 Mar 2024 04:02
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Author:
Andrew J. Durnford
Author:
Azubuike I. Okemefuna
Author:
John Dunbar
Author:
James Galea
Author:
Diederik O. Bulters
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