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Haemoglobin scavenging in intracranial bleeding: biology and clinical implications

Haemoglobin scavenging in intracranial bleeding: biology and clinical implications
Haemoglobin scavenging in intracranial bleeding: biology and clinical implications
Haemoglobin is released into the CNS during the breakdown of red blood cells after intracranial bleeding. Extracellular free haemoglobin is directly neurotoxic. Haemoglobin scavenging mechanisms clear haemoglobin and reduce toxicity; these mechanisms include erythrophagocytosis, haptoglobin binding of haemoglobin, haemopexin binding of haem and haem oxygenase breakdown of haem. However, the capacity of these mechanisms is limited in the CNS, and they easily become overwhelmed. Targeting of haemoglobin toxicity and scavenging is, therefore, a rational therapeutic strategy. In this Review, we summarize the neurotoxic mechanisms of extracellular haemoglobin and the peculiarities of haemoglobin scavenging pathways in the brain. Evidence for a role of haemoglobin toxicity in neurological disorders is discussed, with a focus on subarachnoid haemorrhage and intracerebral haemorrhage, and emerging treatment strategies based on the molecular pathways involved are considered. By focusing on a fundamental biological commonality between diverse neurological conditions, we aim to encourage the application of knowledge of haemoglobin toxicity and scavenging across various conditions. We also hope that the principles highlighted will stimulate research to explore the potential of the pathways discussed. Finally, we present a consensus opinion on the research priorities that will help to bring about clinical benefits.
1759-4758
416-432
Bulters, Diederik
d6f9644a-a32f-45d8-b5ed-be54486ec21d
Gaastra, Ben
c6a69fe5-84a6-4a41-990c-8999afb00822
Zolnourian, Ardalan
5e8d4881-cdfd-4cb1-8eae-b98b13104648
Alexander, Sheila
47c15a44-3ab4-431a-9b9c-71a36feec7fc
Ren, Dianxu
6786b499-ff89-479d-a3a8-38fba114188a
Blackburn, Spiros L.
dbf01e31-f361-458f-bca7-9bc11b8a19a0
Borsody, Mark
cf4b59a9-b150-4c86-91eb-c8cba15ac622
Doré, Sylvain
35207796-1991-4247-bd28-e73a3b6de60a
Galea, James
b4b41adb-980d-41f0-be40-976a6aa2dab7
Iihara, Koji
802c351a-5e2b-4425-9f4e-78d215569b03
Nyquist, Paul
e63d5518-c139-45fa-8694-74a202acd63e
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Bulters, Diederik
d6f9644a-a32f-45d8-b5ed-be54486ec21d
Gaastra, Ben
c6a69fe5-84a6-4a41-990c-8999afb00822
Zolnourian, Ardalan
5e8d4881-cdfd-4cb1-8eae-b98b13104648
Alexander, Sheila
47c15a44-3ab4-431a-9b9c-71a36feec7fc
Ren, Dianxu
6786b499-ff89-479d-a3a8-38fba114188a
Blackburn, Spiros L.
dbf01e31-f361-458f-bca7-9bc11b8a19a0
Borsody, Mark
cf4b59a9-b150-4c86-91eb-c8cba15ac622
Doré, Sylvain
35207796-1991-4247-bd28-e73a3b6de60a
Galea, James
b4b41adb-980d-41f0-be40-976a6aa2dab7
Iihara, Koji
802c351a-5e2b-4425-9f4e-78d215569b03
Nyquist, Paul
e63d5518-c139-45fa-8694-74a202acd63e
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b

Bulters, Diederik, Gaastra, Ben, Zolnourian, Ardalan, Alexander, Sheila, Ren, Dianxu, Blackburn, Spiros L., Borsody, Mark, Doré, Sylvain, Galea, James, Iihara, Koji, Nyquist, Paul and Galea, Ian (2018) Haemoglobin scavenging in intracranial bleeding: biology and clinical implications. Nature Reviews Neurology, 14 (7), 416-432. (doi:10.1038/s41582-018-0020-0).

Record type: Article

Abstract

Haemoglobin is released into the CNS during the breakdown of red blood cells after intracranial bleeding. Extracellular free haemoglobin is directly neurotoxic. Haemoglobin scavenging mechanisms clear haemoglobin and reduce toxicity; these mechanisms include erythrophagocytosis, haptoglobin binding of haemoglobin, haemopexin binding of haem and haem oxygenase breakdown of haem. However, the capacity of these mechanisms is limited in the CNS, and they easily become overwhelmed. Targeting of haemoglobin toxicity and scavenging is, therefore, a rational therapeutic strategy. In this Review, we summarize the neurotoxic mechanisms of extracellular haemoglobin and the peculiarities of haemoglobin scavenging pathways in the brain. Evidence for a role of haemoglobin toxicity in neurological disorders is discussed, with a focus on subarachnoid haemorrhage and intracerebral haemorrhage, and emerging treatment strategies based on the molecular pathways involved are considered. By focusing on a fundamental biological commonality between diverse neurological conditions, we aim to encourage the application of knowledge of haemoglobin toxicity and scavenging across various conditions. We also hope that the principles highlighted will stimulate research to explore the potential of the pathways discussed. Finally, we present a consensus opinion on the research priorities that will help to bring about clinical benefits.

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More information

e-pub ahead of print date: 20 June 2018
Published date: 20 June 2018

Identifiers

Local EPrints ID: 421927
URI: https://eprints.soton.ac.uk/id/eprint/421927
ISSN: 1759-4758
PURE UUID: 74369c57-ef6c-4bfa-81e8-46b3d58e8e83
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 11 Jul 2018 16:30
Last modified: 14 Mar 2019 01:44

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