Pramipexole Protects Against Traumatic Brain Injury-Induced Blood-Brain Barrier (BBB) Dysfunction.

Abstract

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 μM 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 μM 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.

• Authors: Junping Huang, Huan Lan, Changji Xie, Chengcong Wei, Zhen Liu, Zhixi Huang, Zhiyu Zhou, Lei Chen
• Journal: Neurotoxicity research (Neurotox Res) Vol. 40 Issue 4 Pg. 1020-1028 (Aug 2022) ISSN: 1476-3524 [Electronic] United States
• PMID: 35524855 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Occludin
• Pramipexole

Topics

• Animals
• Blood-Brain Barrier (metabolism)
• Brain Injuries, Traumatic (drug therapy)
• Endothelial Cells (metabolism)
• Mice
• Mice, Inbred C57BL
• Occludin (metabolism)
• Pramipexole