Iron Deposition in the Brain After Aneurysmal Subarachnoid Hemorrhage
Iron Deposition in the Brain After Aneurysmal Subarachnoid Hemorrhage
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DOI：
10.1161/strokeaha.121.036645
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发表时间：
2022-05-01
期刊：
影响因子：
8.3
通讯作者：
Boche, Delphine
中科院分区：
文献类型：
--
作者：
Galea, Ian;Durnford, Andrew;Boche, Delphine
背景：动脉瘤性蛛网膜下腔出血（SAH）后，大脑皮层形成血栓并释放血红蛋白。当在细胞外时，血红蛋白对神经元有毒。高局部血红蛋白浓度压倒了表达血红蛋白-触珠蛋白清道夫受体 CD163 的巨噬细胞的清除能力。我们假设 SAH 后铁沉积在皮质中，并与结果相关。方法：进行了两项互补的横断面研究。使用 Perls 铁染色和 CD163、ADAM17（解整合素和金属肽酶结构域 17）、CD68 和 Iba1（离子钙结合接头分子 1）免疫标记对 39 例 SAH（平均发作后间隔为 9 天）和 22 例对照病例的死后脑组织进行研究。与此同时，为了研究皮质铁的持久性及其与临床结果的关系，我们对 21 名 SAH 患者术后 6 个月和 10 名对照个体进行了磁敏感加权成像研究。结果：在蛛网膜下腔出血后不久死亡的患者的脑组织中，铁沉积的分布遵循随着距脑表面距离的增加而减小的梯度。铁位于细胞内（主要在巨噬细胞中，偶尔在小胶质细胞、神经元和神经胶质细胞中）和细胞外。 SAH 后小胶质细胞活化和运动标记物增加，并具有类似的向内递减梯度。在对照组中，CD163 与铁呈正相关，但 SAH 后该相关性消失。在 SAH 幸存者中，SAH 后 6 个月的铁敏感成像证实皮质铁的持续存在，与 SAH 后血栓的大小和位置有关，并与认知结果相关。结论：SAH 后，铁沉积在皮质灰质中的模式反映了与大脑表面和血栓的接近程度，并且与认知结果相关。这些观察结果支持了 SAH 后防止血红蛋白渗透到皮质的治疗策略。
Background: After aneurysmal subarachnoid hemorrhage (SAH), thrombus forms over the cerebral cortex and releases hemoglobin. When extracellular, hemoglobin is toxic to neurones. High local hemoglobin concentration overwhelms the clearance capacity of macrophages expressing the hemoglobin-haptoglobin scavenger receptor CD163. We hypothesized that iron is deposited in the cortex after SAH and would associate with outcome. Methods: Two complementary cross-sectional studies were conducted. Postmortem brain tissue from 39 SAH (mean postictal interval of 9 days) and 22 control cases was studied with Perls' staining for iron and immunolabeling for CD163, ADAM17 (a disintegrin and metallopeptidase domain 17), CD68, and Iba1 (ionized calcium binding adaptor molecule 1). In parallel, to study the persistence of cortical iron and its relationship to clinical outcome, we conducted a susceptibility-weighted imaging study of 21 SAH patients 6 months postictus and 10 control individuals. Results: In brain tissue from patients dying soon after SAH, the distribution of iron deposition followed a gradient that diminished with distance from the brain surface. Iron was located intracellularly (mainly in macrophages, and occasionally in microglia, neurones, and glial cells) and extracellularly. Microglial activation and motility markers were increased after SAH, with a similar inward diminishing gradient. In controls, there was a positive correlation between CD163 and iron, which was lost after SAH. In SAH survivors, iron-sensitive imaging 6 months post-SAH confirmed persistence of cortical iron, related to the size and location of the blood clot immediately after SAH, and associated with cognitive outcome. Conclusions: After SAH, iron deposits in the cortical gray matter in a pattern that reflects proximity to the brain surface and thrombus and is related to cognitive outcome. These observations support therapeutic manoeuvres which prevent the permeation of hemoglobin into the cortex after SAH.