Haemoglobin scavenging in intracranial bleeding: Biology and clinical implications

Diederik Bulters, Ben Gaastra, Ardalan Zolnourian, Sheila Alexander, Dianxu Ren, Spiros L. Blackburn, Mark Borsody, Sylvain Doré, James Galea, Koji Iihara, Paul Nyquist, Ian Galea

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)416-432
Number of pages17
JournalNature Reviews Neurology
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2018

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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