The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid hemorrhage
The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid hemorrhage
Delayed cerebral ischemia resulting from extracellular hemoglobin is an important determinant of outcome in subarachnoid hemorrhage. Hemoglobin is scavenged by the CD163-haptoglobin system in the circulation, but little is known about this scavenging pathway in the human central nervous system. The components of this system were analyzed in normal cerebrospinal fluid and after subarachnoid hemorrhage. The intrathecal presence of the CD163-haptoglobin-hemoglobin scavenging system was unequivocally demonstrated. The resting capacity of the CD163-haptoglobin-hemoglobin system in the normal central nervous system was 50,000 fold lower than that of the circulation. After subarachnoid hemorrhage, the intrathecal CD163-haptoglobin-hemoglobin system was saturated, as shown by the presence of extracellular hemoglobin despite detectable haptoglobin. Hemoglobin efflux from the central nervous system was evident, enabling rescue hemoglobin scavenging by the systemic circulation. Therefore, the central nervous system is not capable of dealing with significant intrathecal hemolysis. Potential therapeutic options to prevent delayed cerebral ischemia ought to concentrate on augmenting the capacity of the intrathecal CD163-haptoglobin-hemoglobin scavenging system and strategies to encourage Hb efflux from the brain.
subarachnoid hemorrhage, hemoglobin scavenging, CD163, haptoglobin, vasospasm, perivascular macrophage
785-792
Galea, James
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Cruickshank, Garth
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Teeling, Jessica L.
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Boche, Delphine
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Garland, Patrick
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Perry, V. Hugh
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Galea, Ian
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June 2012
Galea, James
b4b41adb-980d-41f0-be40-976a6aa2dab7
Cruickshank, Garth
f7656619-ab1d-4cea-be4e-f6bc097736d2
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Garland, Patrick
1d24a0cc-81f2-4ef1-82bd-77d2510e59d6
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Galea, James, Cruickshank, Garth, Teeling, Jessica L., Boche, Delphine, Garland, Patrick, Perry, V. Hugh and Galea, Ian
(2012)
The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid hemorrhage.
Journal of Neurochemistry, 121 (5), .
(doi:10.1111/j.1471-4159.2012.07716.x).
(PMID:22380637)
Abstract
Delayed cerebral ischemia resulting from extracellular hemoglobin is an important determinant of outcome in subarachnoid hemorrhage. Hemoglobin is scavenged by the CD163-haptoglobin system in the circulation, but little is known about this scavenging pathway in the human central nervous system. The components of this system were analyzed in normal cerebrospinal fluid and after subarachnoid hemorrhage. The intrathecal presence of the CD163-haptoglobin-hemoglobin scavenging system was unequivocally demonstrated. The resting capacity of the CD163-haptoglobin-hemoglobin system in the normal central nervous system was 50,000 fold lower than that of the circulation. After subarachnoid hemorrhage, the intrathecal CD163-haptoglobin-hemoglobin system was saturated, as shown by the presence of extracellular hemoglobin despite detectable haptoglobin. Hemoglobin efflux from the central nervous system was evident, enabling rescue hemoglobin scavenging by the systemic circulation. Therefore, the central nervous system is not capable of dealing with significant intrathecal hemolysis. Potential therapeutic options to prevent delayed cerebral ischemia ought to concentrate on augmenting the capacity of the intrathecal CD163-haptoglobin-hemoglobin scavenging system and strategies to encourage Hb efflux from the brain.
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e-pub ahead of print date: 1 March 2012
Published date: June 2012
Keywords:
subarachnoid hemorrhage, hemoglobin scavenging, CD163, haptoglobin, vasospasm, perivascular macrophage
Organisations:
Centre for Biological Sciences, Clinical & Experimental Sciences
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Local EPrints ID: 336195
URI: http://eprints.soton.ac.uk/id/eprint/336195
ISSN: 0022-3042
PURE UUID: aa8a16ef-da13-4a8a-bb65-f389efaedb80
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Date deposited: 19 Mar 2012 12:28
Last modified: 10 Dec 2019 01:49
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Author:
James Galea
Author:
Garth Cruickshank
University divisions
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