Chen Yang, Lin Lin, Bhuiyan Mohammad Iqbal H, He Kai, Jha Roshani, Song Shanshan, Fiesler Victoria M, Begum Gulnaz, Yin Yan, Sun Dandan
Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States.
Front Cell Neurosci. 2023 Dec 1;17:1279385. doi: 10.3389/fncel.2023.1279385. eCollection 2023.
Neuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by recruiting immune cells and maintaining an immune microenvironment in the brain. Despite these critical roles, the exact structural and functional changes to the ChP over post-stroke time remain to be elucidated. We induced ischemic stroke in C57BL/6J mice via transient middle cerebral artery occlusion which led to reduction of cerebral blood flow and infarct stroke. At 1-7 days post-stroke, we detected time-dependent increase in the ChP blood-CSF barrier permeability to albumin, tight-junction damage, and dynamic changes of SPAK-NKCC1 protein complex, a key ion transport regulatory system for CSF production and clearance. A transient loss of SPAK protein complex but increased phosphorylation of the SPAK-NKCC1 complex was observed in both lateral ventricle ChPs. Most interestingly, stroke also triggered elevation of proinflammatory mRNA and its protein as well as infiltration of anti-inflammatory myeloid cells in ChP at day 5 post-stroke. These findings demonstrate that ischemic strokes cause significant damage to the ChP blood-CSF barrier, contributing to neuroinflammation in the subacute stage.
神经炎症是一种与许多神经系统疾病相关的病理事件，包括痴呆和中风。脉络丛（ChP）是脑室中的一个关键结构，它分泌脑脊液（CSF），形成血脑屏障，并通过招募免疫细胞和维持大脑中的免疫微环境来应对疾病状况。尽管具有这些关键作用，但中风后脉络丛的确切结构和功能变化仍有待阐明。我们通过短暂性大脑中动脉闭塞在C57BL/6J小鼠中诱导缺血性中风，这导致脑血流量减少和梗死性中风。在中风后1 - 7天，我们检测到脉络丛血脑屏障对白蛋白的通透性随时间增加、紧密连接受损以及SPAK-NKCC1蛋白复合物（脑脊液产生和清除的关键离子转运调节系统）的动态变化。在双侧脑室脉络丛中均观察到SPAK蛋白复合物短暂缺失，但SPAK-NKCC1复合物的磷酸化增加。最有趣的是，中风还在中风后第5天引发了脉络丛中促炎mRNA及其蛋白的升高以及抗炎髓样细胞的浸润。这些发现表明，缺血性中风会对脉络丛血脑屏障造成显著损伤，导致亚急性期的神经炎症。
