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dl-3-n-丁基苯酞可保持慢性脑低灌注小鼠的脑白质完整性并减轻认知障碍。

dl-3-n-butylphthalide preserves white matter integrity and alleviates cognitive impairment in mice with chronic cerebral hypoperfusion.

机构信息

Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.

出版信息

CNS Neurosci Ther. 2019 Sep;25(9):1042-1053. doi: 10.1111/cns.13189. Epub 2019 Jul 23.

DOI:10.1111/cns.13189
PMID:31334611
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6698981/
Abstract

AIMS

Effects of dl-3-n-butylphthalide (NBP) on white matter damage and cognitive impairment in vascular cognitive impairment (VCI) have not been well studied. This study aimed to investigate the effects of NBP treatment on chronic cerebral hypoperfusion-induced white matter lesions and cognitive dysfunction in mice.

METHODS

Mice were subjected to bilateral common carotid artery stenosis (BCAS) for over 30 days. The cerebral blood flow was detected using a laser Doppler flowmetry. Cognitive functions were assessed by several behavioral tests. We also evaluated the effects of NBP on the blood-brain barrier (BBB) disruption and reactive astrogliosis, using Evans Blue extravasation, Western blot, CBA, and immunofluorescence in BCAS mice and cultured astrocytes.

RESULTS

The results indicated that NBP treatment attenuated spatial memory dysfunction while promoted cerebral perfusion and white matter integrity in BCAS mice. Moreover, NBP treatment prevented BBB leakage and damage of endothelial cells, as well as disruption of endothelial tight junctions. Furthermore, NBP administration effectively decreased the number of activated astrocytes and pro-inflammatory cytokines, as well as the production of MMPs, in BCAS-induced mice and LPS-stimulated astrocytes.

CONCLUSION

Our results indicated that NBP represents a promising therapy for chronic cerebral hypoperfusion-induced white matter damage and cognitive impairment.

摘要

目的

dl-3-正丁基苯酞（NBP）对血管性认知障碍（VCI）患者的白质损伤和认知障碍的影响尚未得到充分研究。本研究旨在探讨 NBP 治疗对慢性大脑低灌注诱导的小鼠白质病变和认知功能障碍的影响。

方法

通过双侧颈总动脉狭窄（BCAS）模型对小鼠进行处理 30 余天。使用激光多普勒血流仪检测脑血流。通过多种行为测试评估认知功能。我们还通过 Evans Blue 外渗、Western blot、CBA 和免疫荧光等方法，评估了 NBP 对 BCAS 小鼠和培养星形胶质细胞中血脑屏障（BBB）破坏和反应性星形胶质细胞增生的影响。

结果

结果表明，NBP 治疗可改善空间记忆功能障碍，同时促进 BCAS 小鼠的脑灌注和白质完整性。此外，NBP 治疗可防止 BBB 渗漏和内皮细胞损伤，以及内皮紧密连接的破坏。此外，NBP 给药可有效减少 BCAS 诱导的小鼠和 LPS 刺激的星形胶质细胞中活化星形胶质细胞和促炎细胞因子的数量，以及 MMPs 的产生。

结论

我们的结果表明，NBP 可能是治疗慢性大脑低灌注诱导的白质损伤和认知障碍的一种有前途的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/a2dcac2ac2cc/CNS-25-1042-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/9a0b6be3bab6/CNS-25-1042-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/5b9294df9bd3/CNS-25-1042-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/5fe45fc4511a/CNS-25-1042-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/6ca1ffdb2f2d/CNS-25-1042-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/ae0497d1f5af/CNS-25-1042-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/a2dcac2ac2cc/CNS-25-1042-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/9a0b6be3bab6/CNS-25-1042-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/5b9294df9bd3/CNS-25-1042-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/5fe45fc4511a/CNS-25-1042-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/6ca1ffdb2f2d/CNS-25-1042-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/ae0497d1f5af/CNS-25-1042-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6f7/6698981/a2dcac2ac2cc/CNS-25-1042-g006.jpg

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