Durnford A, Dunbar J, Galea J, Bulters D, Nicoll J A R, Boche D, Galea I
Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK,
Acta Neurochir Suppl. 2015;120:51-4. doi: 10.1007/978-3-319-04981-6_9.
Rapid and effective clearance of cell-free haemoglobin after subarachnoid haemorrhage (SAH) is important to prevent vasospasm and neurotoxicity and improve long-term outcome. Haemoglobin is avidly bound by haptoglobin, and the complex is cleared by CD163 expressed on the membrane surface of macrophages. We studied the kinetics of haemoglobin and haptoglobin in cerebrospinal fluid after SAH. We show that haemoglobin levels rise gradually after SAH. Haptoglobin levels rise acutely with aneurysmal rupture as a result of injection of blood into the subarachnoid space. Although levels decline as haemoglobin scavenging occurs, complete depletion of haptoglobin does not occur and levels start rising again, indicating saturation of CD163 sites available for haptoglobin-haemoglobin clearance. In a preliminary neuropathological study we demonstrate that meningeal CD163 expression is upregulated after SAH, in keeping with a proinflammatory state. However, loss of CD163 occurs in meningeal areas with overlying blood compared with areas without overlying blood. Becauses ADAM17 is the enzyme responsible for shedding membrane-bound CD163, its inhibition may be a potential therapeutic strategy after SAH.
蛛网膜下腔出血（SAH）后迅速有效地清除游离血红蛋白对于预防血管痉挛和神经毒性以及改善长期预后至关重要。血红蛋白与触珠蛋白紧密结合，该复合物由巨噬细胞膜表面表达的CD163清除。我们研究了SAH后脑脊液中血红蛋白和触珠蛋白的动力学。我们发现SAH后血红蛋白水平逐渐升高。由于血液注入蛛网膜下腔，触珠蛋白水平在动脉瘤破裂时急剧升高。尽管随着血红蛋白清除，其水平下降，但触珠蛋白并未完全耗尽，且水平再次开始上升，这表明可用于触珠蛋白 - 血红蛋白清除的CD163位点已饱和。在一项初步神经病理学研究中，我们证明SAH后脑膜CD163表达上调，这与促炎状态一致。然而，与无血液覆盖的区域相比，有血液覆盖的脑膜区域出现CD163缺失。由于ADAM17是负责脱落膜结合型CD163的酶，抑制该酶可能是SAH后的一种潜在治疗策略。
