Neuroinflammation is involved in the onset or progression of various neurodegenerative diseases. Initiation of neuroinflammation is triggered by endogenous substances (damage-associated molecular patterns) and/or exogenous pathogens. Activation of glial cells (microglia and astrocytes) is widely recognized as a hallmark of neuroinflammation and triggers the release of proinflammatory cytokines, leading to neurotoxicity and neuronal dysfunction. Another feature associated with neuroinflammatory diseases is impairment of the blood-brain barrier (BBB). The BBB, which is composed of brain endothelial cells connected by tight junctions, maintains brain homeostasis and protects neurons. Impairment of this barrier allows trafficking of immune cells or plasma proteins into the brain parenchyma and subsequent inflammatory processes in the brain. Besides neurons, activated glial cells also affect BBB integrity. Therefore, BBB dysfunction can amplify neuroinflammation and act as a key process in the development of neuroinflammation. BBB integrity is determined by the integration of multiple signaling pathways within brain endothelial cells through intercellular communication between brain endothelial cells and brain perivascular cells (pericytes, astrocytes, microglia, and oligodendrocytes). For prevention of BBB disruption, both cellular components, such as signaling molecules in brain endothelial cells, and non-cellular components, such as inflammatory mediators released by perivascular cells, should be considered. Thus, understanding of intracellular signaling pathways that disrupt the BBB can provide novel treatments for neurological diseases associated with neuroinflammation. In this review, we discuss current knowledge regarding the underlying mechanisms involved in BBB impairment by inflammatory mediators released by perivascular cells.

神经炎症与各种神经退行性疾病的发生或进展有关。神经炎症的启动由内源性物质（损伤相关分子模式）和/或外源性病原体触发。神经胶质细胞（小胶质细胞和星形胶质细胞）的激活被广泛认为是神经炎症的标志，并触发促炎细胞因子的释放，导致神经毒性和神经元功能障碍。与神经炎性疾病相关的另一个特征是血脑屏障 (BBB) 受损。BBB 由紧密连接的脑内皮细胞组成，维持脑内稳态并保护神经元。这种屏障的受损允许免疫细胞或血浆蛋白运输到脑实质和随后的大脑炎症过程。除了神经元，活化的神经胶质细胞也会影响 BBB 的完整性。因此，BBB 功能障碍可以放大神经炎症并作为神经炎症发展的关键过程。BBB 的完整性是由脑内皮细胞内的多个信号通路通过脑内皮细胞和脑血管周围细胞（周细胞、星形胶质细胞、小胶质细胞和少突胶质细胞）之间的细胞间通讯整合决定的。为防止 BBB 破坏，应考虑细胞成分（如脑内皮细胞中的信号分子）和非细胞成分（如血管周围细胞释放的炎症介质）。因此，了解破坏 BBB 的细胞内信号通路可以为与神经炎症相关的神经系统疾病提供新的治疗方法。