Pramipexole Protects Against Traumatic Brain Injury-Induced Blood-Brain Barrier (BBB) Dysfunction
Pramipexole Protects Against Traumatic Brain Injury-Induced Blood-Brain Barrier (BBB) Dysfunction
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DOI：
10.1007/s12640-022-00495-6
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发表时间：
2022-05-07
影响因子：
3.7
通讯作者：
Chen, Lei
中科院分区：
文献类型：
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作者：
Huang, Junping;Lan, Huan;Chen, Lei
创伤性脑损伤（TBI）是一种伴有血脑屏障（BBB）功能障碍的严重脑损伤疾病。 BBB 由脑微血管内皮细胞 (BMEC)、星形胶质细胞末端、周细胞和基底膜组成。 BMEC 表达的紧密连接蛋白在保持 BBB 完整性方面发挥着重要作用。普拉克索是一种选择性多巴胺激动剂，用于治疗帕金森病，最近被声称具有神经保护能力。本研究将进一步探讨普拉克索对紧密连接和血脑屏障完整性的影响，为 TBI 引起的血脑屏障损伤提供潜在的治疗策略。建立小鼠TBI模型，表现为脑含水量升高、Garcia评分下降、转棒试验潜伏期缩短、脑皮质病理改变加剧、炎症因子过度释放等。普拉克索治疗后，神经功能缺陷、行为障碍和加重的病理变化均得到显着逆转，同时血脑屏障通透性减轻，重要的紧密连接蛋白occludin上调。采用bEnd.3细胞划痕法建立TBI模型细胞。用10和20μM普拉克索刺激细胞，然后暴露于TBI。在暴露于TBI的细胞中观察到FITC-葡聚糖荧光强度增加、TEER值降低以及occludin和KLF2下调，所有这些都被10和20μM普拉克索大大逆转。此外，在KLF2沉默的bEnd.3细胞中，普拉克索对内皮通透性的保护能力和occludin的表达水平都被显着消除。总的来说，我们的结果表明普拉克索通过介导 KLF2 来预防 TBI 诱导的 BBB 功能障碍。
Traumatic brain injury (TBI) is a severe disease of brain damage accompanied by blood-brain barrier (BBB) dysfunction. The BBB is composed of brain microvascular endothelial cells (BMECs), astrocyte terminus, pericytes, and a basement membrane. Tight junction proteins expressed by BMECs play important roles in preserving BBB integrity. Pramipexole is a selective dopamine agonist applied for treating Parkinson's disease and has been recently claimed with neuroprotective capacity. This study will further explore the impact of Pramipexole on tight junctions and BBB integrity to provide the potential treatment strategy for TBI-induced BBB damage. The TBI model was established in mice and was identified by the promoted brain water content, declined Garcia scores, reduced latency of the rotarod test, aggravated pathological changes in the brain cortex, and excessively released inflammatory factors. After treatment with Pramipexole, the neurofunctional deficits, behavioral disability, and aggravated pathological changes were dramatically reversed, accompanied by the alleviated BBB permeability, and upregulated occludin, an important tight junction protein. TBI model cells were established by the scratching bEnd.3 cells method. Cells were stimulated with 10 and 20 mu M Pramipexole, followed by exposure to TBI. Increased fluorescence intensity of FITC-dextran, reduced value of TEER, and downregulated occludin and KLF2 were observed in TBI-exposed cells, all of which were greatly reversed by 10 and 20 mu M Pramipexole. Furthermore, in KLF2-silenced bEnd.3 cells, the protective ability of Pramipexole against endothelial permeability and the expression level of occludin were dramatically abolished. Collectively, our results suggest that Pramipexole protected against TBI-induced BBB dysfunction by mediating KLF2.