Department of Histology, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
'Mina Minovici' National Institute for Legal Medicine, Bucharest, Romania.
Eur J Neurol. 2022 Dec;29(12):3676-3692. doi: 10.1111/ene.15545. Epub 2022 Oct 1.
In the central nervous system, a multitude of changes have been described associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, such as microglial activation, perivascular lymphocyte cuffing, hypoxic-ischaemic changes, microthrombosis, infarcts or haemorrhages. It was sought here to assess the vascular basement membranes (vBMs) and surrounding perivascular astrocytes for any morphological changes in acute respiratory syndrome (coronavirus disease 2019, COVID-19) patients.
The light microscopy morphology of the vBMs and perivascular astrocytes from brains of 14 patients with confirmed SARS-CoV-2 infection was analysed and compared to four control patients utilizing fluorescent immunohistochemistry for collagen IV and astrocytes (GFAP), endothelia (CD31), tight junction 1 (TJ1) adhesion protein, as well as the aquaporin 4 (AQP4) water channel. On 2D and 3D deconvoluted images from the cortex and white matter, vessel densities, diameters, degree of gliosis, collagen IV/GFAP and GFAP/AQP4 colocalizations were calculated, as well as the fractal dimension of astrocytes and vBMs viewed in tangential planes.
Fractal dimension analysis of the GFAP-stained astrocytes revealed lower branching complexities and decreased GFAP/collagen IV colocalization for COVID-19 patients. Interestingly, vBMs showed significantly increased irregularities (fractal dimension values) compared to controls. Vessel diameters were increased in COVID-19 cases, especially for the white matter, TJ1 protein decreased its colocalization with the endothelia, and AQP4 reduced its co-expression in astrocytes.
Our data on the irregularity of the basement membranes, loss of endothelial tight junction, reduction of the astrocyte end-feet and decrease of AQP4 suggest subtle morphological changes of the blood-brain barrier in COVID-19 brains that could be linked with indirect inflammatory signalling or hypoxia/hypercapnia.
在中枢神经系统中，已经描述了与严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染相关的多种变化，如小胶质细胞激活、血管周围淋巴细胞袖套、缺氧缺血性改变、微血栓形成、梗死或出血。在这里，我们试图评估急性呼吸综合征（冠状病毒病 2019，COVID-19）患者血管基底膜（vBM）和周围血管周星形胶质细胞是否有任何形态变化。
利用荧光免疫组织化学法对 14 例确诊 SARS-CoV-2 感染患者的 vBM 和血管周星形胶质细胞的光镜形态进行分析，并与 4 例对照患者进行比较，检测胶原 IV 和星形胶质细胞（GFAP）、内皮细胞（CD31）、紧密连接蛋白 1（TJ1）、水通道蛋白 4（AQP4）。对皮质和白质的 2D 和 3D 去卷积图像进行分析，计算血管密度、直径、胶质增生程度、胶原 IV/GFAP 和 GFAP/AQP4 共定位以及在切向平面观察的星形胶质细胞和 vBM 的分形维数。
COVID-19 患者 GFAP 染色星形胶质细胞的分形维数分析显示分支复杂性降低，GFAP/胶原 IV 共定位减少。有趣的是，与对照组相比，vBM 显示出明显增加的不规则性（分形维数值）。COVID-19 病例的血管直径增加，尤其是白质，TJ1 蛋白与其内皮细胞的共定位减少，AQP4 在星形胶质细胞中的共表达减少。
我们关于基底膜不规则、内皮紧密连接丧失、星形胶质细胞终足减少和 AQP4 减少的研究数据表明，COVID-19 大脑中的血脑屏障存在细微的形态变化，这些变化可能与间接炎症信号或缺氧/高碳酸血症有关。
