Division of Neurosurgery, St. Michael's Hospital, Toronto, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
J Cereb Blood Flow Metab. 2021 Aug;41(8):1842-1857. doi: 10.1177/0271678X20980296. Epub 2021 Jan 14.
The distribution and clearance of erythrocytes after subarachnoid hemorrhage (SAH) is poorly understood. We aimed to characterize the distribution of erythrocytes after SAH and the cells involved in their clearance. To visualize erythrocyte distribution, we injected fluorescently-labelled erythrocytes into the prechiasmatic cistern of mice. 10 minutes after injection, we found labelled erythrocytes in the subarachnoid space and ventricular system, and also in the perivascular spaces surrounding large penetrating arterioles. 2 and 5 days after SAH, fluorescence was confined within leptomeningeal and perivascular cells. We identified the perivascular cells as perivascular macrophages based on their morphology, location, Iba-1 immunoreactivity and preferential uptake of FITC-dextran. We subsequently depleted meningeal and perivascular macrophages 2 days before or 3 hours after SAH with clodronate liposomes. At day 5 after SAH, we found increased blood deposition in mice treated prior to SAH, but not those treated after. Treatment post-SAH improved neurological scoring, reduced neuronal cell death and perivascular inflammation, whereas pre-treatment only reduced perivascular inflammation. Our data indicate that after SAH, erythrocytes are distributed throughout the subarachnoid space extending into the perivascular spaces of parenchymal arterioles. Furthermore, meningeal and perivascular macrophages are involved in erythrocyte uptake and play an important role in outcome after SAH.
蛛网膜下腔出血（SAH）后红细胞的分布和清除机制尚不清楚。本研究旨在明确 SAH 后红细胞的分布特征，以及参与清除的细胞。为了可视化红细胞的分布，我们将荧光标记的红细胞注入小鼠视交叉前池。注血后 10 分钟，我们发现标记的红细胞分布在蛛网膜下腔和脑室系统，也存在于大穿透性动脉周围的血管周围间隙。SAH 后 2 天和 5 天，荧光局限于软脑膜和血管周围细胞。基于形态学、位置、Iba-1 免疫反应性和 FITC-葡聚糖的优先摄取，我们将这些血管周围细胞鉴定为血管周巨噬细胞。随后，我们在 SAH 前 2 天或后 3 小时用氯膦酸盐脂质体耗竭脑膜和血管周围巨噬细胞。在 SAH 后 5 天，我们发现预先治疗的小鼠的血液沉积增加，但在 SAH 后治疗的小鼠中没有这种情况。SAH 后治疗可改善神经评分，减少神经元细胞死亡和血管周围炎症，而预先治疗仅能减少血管周围炎症。我们的数据表明，SAH 后，红细胞分布在整个蛛网膜下腔，并延伸到脑实质动脉的血管周围间隙。此外，脑膜和血管周围巨噬细胞参与了红细胞的摄取，在 SAH 后的转归中发挥了重要作用。
