title: The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid hemorrhage.
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 CNS. 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 CNS 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 CNS was evident, enabling rescue hemoglobin scavenging by the systemic circulation. Therefore, the CNS 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 hemoglobin efflux from the brain.
authors.affiliation: Brain Injury Research Group, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Manchester, UK. i.galea@soton.ac.uk
authors.forename: James
authors.initials: J
authors.lastname: Galea
authors.forename: Garth
authors.initials: G
authors.lastname: Cruickshank
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Teeling
authors.forename: Delphine
authors.initials: D
authors.lastname: Boche
authors.forename: Patrick
authors.initials: P
authors.lastname: Garland
authors.forename: V Hugh
authors.initials: VH
authors.lastname: Perry
authors.forename: Ian
authors.initials: I
authors.lastname: Galea
mesh_terms: D015703:Antigens, CD / Q000134:cerebrospinal fluid*; D015214:Antigens, Differentiation, Myelomonocytic / Q000134:cerebrospinal fluid*; D002545:Brain Ischemia / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006242:Haptoglobins / Q000134:cerebrospinal fluid*; D006454:Hemoglobins / Q000134:cerebrospinal fluid*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000150:complications / Q000276:immunology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface