The heme-hemopexin scavenging system is active in the brain, and associates with outcome after subarachnoid hemorrhage

• Main Authors: Garland, Patrick (Author), Durnford, Andrew J. (Author), Okemefuna, Azubuike I. (Author), Dunbar, John (Author), Nicoll, James A.R (Author), Galea, James (Author), Boche, Delphine (Author), Bulters, Diederik O. (Author), Galea, Ian (Author)
• Format: Article
• Language: English
• Published: 2016-03.
• Subjects: Article
• Online Access: Get fulltext; Get fulltext

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.