Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Mediators Inflamm. 2020 Aug 1;2020:1921826. doi: 10.1155/2020/1921826. eCollection 2020.
Neuroinflammation plays a key role in the occurrence and development of neurodegenerative diseases. Microglia, the resident immune cells in the brain, have been recognized to contribute to neuroinflammation. Previous studies have shown that activated mast cells may be involved in surgery-induced neuroinflammation and neuronal apoptosis by using pharmacological methods. This study is aimed at ascertaining the exactly role of mast cells on neuroinflammation with the mast cell-deficient mice. Adult male C57BL6/J wild-type (WT) and mast cell-deficient (C57BL6/J KitWsh/Wsh (Wsh)) mice underwent tibial fracture surgery. Blood-brain barrier (BBB) breakdown, microglial activation, and neuroinflammatory levels were examined at 1 day after surgery. Surgery-induced BBB breakdown, microglial activation, and neuroinflammatory levels were significantly, pharmacologically reduced using a mast cell stabilizer, cromolyn sodium in WT mice ( < 0.05). These results were reproduced with mast cell deficiency. WT mice administered intraventricularly with cromolyn exhibited reduced BBB breakdown, microglial activation, and neuroinflammatory levels versus vehicle ( < 0.05). But there was no effect of cromolyn versus vehicle in Wsh mice, clarifying the specificity of cromolyn on brain mast cells. These findings demonstrated that activated mast cells promote surgery-induced BBB breakdown and neuroinflammation in mice, and open up a new therapeutic target for neuroinflammation-related diseases.
神经炎症在神经退行性疾病的发生和发展中起着关键作用。小胶质细胞是大脑中的固有免疫细胞，已被认为有助于神经炎症。先前的研究表明，通过药理学方法，激活的肥大细胞可能参与手术诱导的神经炎症和神经元凋亡。本研究旨在通过肥大细胞缺陷小鼠确定肥大细胞在神经炎症中的确切作用。成年雄性 C57BL6/J 野生型 (WT) 和肥大细胞缺陷型 (C57BL6/J KitWsh/Wsh (Wsh)) 小鼠接受胫骨骨折手术。手术后 1 天检查血脑屏障 (BBB) 破裂、小胶质细胞激活和神经炎症水平。在 WT 小鼠中，使用肥大细胞稳定剂色甘酸钠可显著（<0.05）降低手术诱导的 BBB 破裂、小胶质细胞激活和神经炎症水平。在肥大细胞缺陷型小鼠中也复制了这些结果。与载体相比，WT 小鼠脑室给予色甘酸钠可降低 BBB 破裂、小胶质细胞激活和神经炎症水平（<0.05）。但是，在 Wsh 小鼠中，色甘酸钠与载体相比没有效果，这阐明了色甘酸钠对脑肥大细胞的特异性。这些发现表明，激活的肥大细胞促进了小鼠手术诱导的 BBB 破裂和神经炎症，并为神经炎症相关疾病开辟了新的治疗靶点。
