Garland Patrick, Durnford Andrew J, Okemefuna Azubuike I, Dunbar John, Nicoll James A R, Galea James, Boche Delphine, Bulters Diederik O, Galea Ian
From the Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (P.G., J.D., J.A.R.N., D.B., D.O.B., I.G.); Neurosurgery, Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom (A.J.D., D.O.B., I.G.); R&D, Bio Products Laboratory Limited, Hertfordshire, United Kingdom (A.I.O.); and the Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom (J.G.).
Stroke. 2016 Mar;47(3):872-6. doi: 10.1161/STROKEAHA.115.011956. Epub 2016 Jan 14.
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.
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.
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 early in the cerebrospinal fluid. When the blood-brain barrier was compromised after SAH, serum hemopexin level was lower, suggesting heme transfer to the circulation for peripheral CD91 scavenging.
The CD91-heme-hemopexin scavenging system is important after SAH and merits further study as a potential prognostic marker and therapeutic target.
蛛网膜下腔出血（SAH）后的长期预后可能与细胞毒性血红素有关。游离血红素与血红素结合蛋白结合，并被CD91迅速清除。我们推测大脑中的血红素清除可能与出血后的预后相关。
使用SAH患者和对照个体的脑脊液和组织，采用酶联免疫吸附测定（ELISA）、超高效液相色谱法和免疫组织化学检查颅内CD91-血红素结合蛋白系统的活性。
在对照个体中，脑脊液中的血红素结合蛋白主要在鞘内合成。SAH后，三分之一的病例脑脊液中的血红素结合蛋白水平较高，这些患者发生迟发性脑缺血的可能性更高，神经功能预后更差。SAH后颅内CD91-血红素结合蛋白系统活跃，因为CD91与脑组织中的铁沉积呈正相关。SAH后血红素-血红素结合蛋白的摄取迅速饱和，因为结合的血红素在脑脊液中早期积聚。SAH后血脑屏障受损时，血清血红素结合蛋白水平较低，提示血红素转移至循环系统以便外周CD91清除。
SAH后CD91-血红素-血红素结合蛋白清除系统很重要，作为一种潜在的预后标志物和治疗靶点值得进一步研究。
