Traumatic brain injury (TBI) is one of the major health problems worldwide that causes death or permanent disability through primary and secondary damages in the brain. TBI causes primary brain damage and activates glial cells and immune and inflammatory cells, including mast cells in the brain associated with neuroinflammatory responses that cause secondary brain damage. Though the survival rate and the neurological deficiencies have shown significant improvement in many TBI patients with newer therapeutic options, the underlying pathophysiology of TBI-mediated neuroinflammation, neurodegeneration, and cognitive dysfunctions is understudied. In this study, we analyzed mast cells and neuroinflammation in weight drop-induced TBI. We analyzed mast cell activation by toluidine blue staining, serum chemokine C-C motif ligand 2 (CCL2) level by enzyme-linked immunosorbent assay (ELISA), and proteinase-activated receptor-2 (PAR-2), a mast cell and inflammation-associated protein, vascular endothelial growth factor receptor 2 (VEGFR2), and blood-brain barrier tight junction-associated claudin 5 and Zonula occludens-1 (ZO-1) protein expression in the brains of TBI mice. Mast cell activation and its numbers increased in the brains of 24 h and 72 h TBI when compared with sham control brains without TBI. Mouse brains after TBI show increased CCL2, PAR-2, and VEGFR2 expression and derangement of claudin 5 and ZO-1 expression as compared with sham control brains. TBI can cause mast cell activation, neuroinflammation, and derangement of tight junction proteins associated with increased BBB permeability. We suggest that inhibition of mast cell activation can suppress neuroimmune responses and glial cell activation-associated neuroinflammation and neurodegeneration in TBI.

中文翻译：

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急性创伤性脑损伤中的肥大细胞活化，神经炎症和紧密连接蛋白排列异常。

颅脑外伤（TBI）是世界范围内的主要健康问题之一，它通过对大脑的初次和二次损伤而导致死亡或永久性残疾。TBI引起原发性脑损伤并激活神经胶质细胞以及免疫和炎性细胞，包括与引起继发性脑损伤的神经炎症反应相关的大脑肥大细胞。尽管在具有较新治疗选择的许多TBI患者中，生存率和神经系统缺陷已显示出明显的改善，但仍未研究TBI介导的神经炎症，神经退行性变和认知功能障碍的潜在病理生理。在这项研究中，我们分析了体重减轻引起的TBI中的肥大细胞和神经炎症。我们通过甲苯胺蓝染色分析了肥大细胞的活化，酶联免疫吸附测定（ELISA）检测血清趋化因子CC基序配体2（CCL2）的水平，以及蛋白酶激活受体2（PAR-2），肥大细胞和炎症相关蛋白，血管内皮生长因子受体2（VEGFR2） ），以及TBI小鼠大脑中血脑屏障紧密连接相关的claudin 5和Zonula occludens-1（ZO-1）蛋白表达。与没有TBI的假对照组相比，TBI在24小时和72小时的大脑中肥大细胞激活及其数量增加。与假手术对照脑相比，TBI后的小鼠脑显示CCL2，PAR-2和VEGFR2表达增加，claudin 5和ZO-1表达紊乱。TBI可以引起肥大细胞活化，神经炎症和与BBB通透性增加相关的紧密连接蛋白的紊乱。