Abstract：
Bezafibrate (BEZ) has displayed a wide range of neuroprotective effects in different types of neurological diseases. However, its pharmacological function in traumatic brain injury (TBI) is still unknown. In the current study, a TBI model was constructed in mice to examine the potential beneficial roles of BEZ. After TBI, mice were daily dieted with BEZ or vehicle solution. The motor function, learning and memory, brain edema, vascular inflammatory factors, the integrity of the blood-brain barrier (BBB), and the expression of the tight junction zona occludens 1 (ZO-1) were assessed. The findings demonstrate that after TBI, BEZ treatment significantly promoted the recovery of motor function and cognitive function deficits. Moreover, BEZ attenuated brain edema by reducing the levels of brain water content. We also found that administration of BEZ alleviated cerebral vascular pro-inflammation by suppressing the expression of ICAM-1, VCAM-1, and E-selectin. Notably, BEZ improved the impaired BBB integrity in TBI mice by restoring the expression of the tight junction (TJ) protein ZO-1. Further in vitro experiments show that treatment with BEZ prevented the aggravation of endothelial permeability and restored the reduction of trans-epithelial electrical resistance (TEER) as well as the expression of ZO-1 in TBI-exposed brain bEnd.3 cells. Mechanistically, we prove that the protective effects of BEZ are mediated by AMPK. Based on these findings, we conclude that BEZ improves TBI-induced BBB injury and it might be considered for the treatment or management of TBI.
摘要：
苯扎贝特（BEZ）在不同类型的神经系统疾病中显示出广泛的神经保护作用。然而,其在创伤性脑损伤（TBI）中的药理功能尚不清楚。在目前的研究中,在小鼠中构建TBI模型以检查BEZ的潜在有益作用。在TBI之后,每天用BEZ或媒介物溶液对小鼠进行节食。电机功能，学习和记忆，脑水肿,血管炎症因子,血脑屏障（BBB）的完整性，并评估了紧密连接带闭塞1（ZO-1）的表达。研究结果表明，在TBI之后，BEZ治疗显著促进运动功能和认知功能缺损的恢复。此外，BEZ通过降低脑含水量来减轻脑水肿。我们还发现，BEZ的给药通过抑制ICAM-1，VCAM-1和E-选择素的表达来减轻脑血管炎症。值得注意的是,BEZ通过恢复紧密连接（TJ）蛋白ZO-1的表达改善了TBI小鼠受损的BBB完整性。进一步的体外实验表明，用BEZ处理可以防止内皮通透性的恶化，并恢复TBI暴露的脑bEnd.3细胞中跨上皮电阻（TEER）的降低以及ZO-1的表达。机械上,我们证明BEZ的保护作用是由AMPK介导的。基于这些发现,我们得出的结论是，BEZ可以改善TBI引起的BBB损伤，可以考虑将其用于TBI的治疗或管理。
