Department of Medical Sciences and Public Health, University of Cagliari, Electron Microscopy Laboratory, Division Pathological Anatomy, Cagliari, Italy.
Eur Rev Med Pharmacol Sci. 2022 Apr;26(8):3025-3029. doi: 10.26355/eurrev_202204_28633.
Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2. The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses.
Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (H&E) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution.
We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries.
Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells.
先前的研究已经证实了 SARS-CoV-2 进入人体细胞的关键机制。众所周知，ACE2 是可以标记感染开始的受体。有鉴于此，一般认为表达 ACE2 水平较高的器官风险更高，而表达 ACE2 水平较低的器官则应受到某种程度的保护。这一点——如果与大脑中 ACE2 表达细胞的稀缺性有关——似乎与感染 ACE2 后出现多种神经症状相矛盾。本研究旨在分析人类大脑中 ACE2 的表达，重点关注脉络丛。
从十名胎儿和十名成人的尸检中获得了二十个脑组织样本。所有样本均选择包含脉络丛。标本用 10%福尔马林固定，常规处理并石蜡包埋。用苏木精和伊红（H&E）染色和商业抗人 ACE2 兔单克隆抗体（稀释度为 1:100）进行免疫组织化学染色。
我们通过免疫组织化学分析了 20 个样本，结果表明，就胎儿样本而言，脉络丛的黏液基质和胎儿内皮细胞中检测到 ACE2 强烈反应。在胎儿和成人的上皮细胞、皮质神经元和神经胶质细胞中均未检测到 ACE2 标志物。而在成人脉络丛中也检测到 ACE2 的强烈但选择性反应，主要定位于脉络丛毛细血管的内皮细胞中。
我们的研究表明 ACE2 在胎儿和成人脑脉络丛中表达强烈。这一新的组织病理学发现可能阐明了人类大脑对 SARS-COV-2 感染的易感性。我们的数据表明脉络丛是病毒进入人脑的入口；因此，SARS-CoV-2 通过脉络丛进入脑脊液可能代表了这种冠状病毒对脑细胞造成直接损伤的机制。
