Heme–Hemopexin Scavenging Is Active in the Brain and Associates With Outcome After Subarachnoid Hemorrhage

Background and Purpose—Long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Free heme is bound by hemopexin and rapidly scavenged by CD91. We hypothesized that heme scavenging in the brain would be associated with outcome after hemorrhage. Methods—Using cerebrospinal fluid and tissue from patients with SAH and control individuals, the activity of the intracranial CD91–hemopexin system was examined using ELISA, ultrahigh performance liquid chromatography, and immunohistochemistry. Results—In control individuals, cerebrospinal fluid hemopexin was mainly synthesized intrathecally. After SAH, cerebrospinal fluid hemopexin was high in one third of cases, and these patients had a higher probability of delayed cerebral ischemia and poorer neurological outcome. The intracranial CD91–hemopexin system was active after SAH because CD91 positively correlated with iron deposition in brain tissue. Heme–hemopexin uptake saturated rapidly after SAH because bound heme accumulated ...