Vascular protection and regenerative effects of intranasal DL-3-N-butylphthalide treatment after ischaemic stroke in mice

• Type of Material: Article
• Authors: Mengyao Qu, Capital Medical University; Jingjie Zhao, Capital Medical University; Yingying Zhao, Capital Medical University; Jinmei Sun, Capital Medical University; Ling Liu, China National GeneBank; Ling Wei, Emory University; Yongbo Zhang, Capital Medical University
• Language: English
• Date: 2021-03-01
• Publisher: BMJ Publishing Company
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2021.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/svn-2020-000364
• Title of Journal or Parent Work: Stroke and Vascular Neurology
• Volume: 6
• Issue: 1
• Start Page: 74
• End Page: 79
• Grant/Funding Information: This study was funded by the National Natural Science Foundation of China (81371355 to YZ, 81500989 to YZ, 81671191 to YZ and 81820108012 to LL).
• Keywords: stroke; drug; brain; Science & Technology; Life Sciences & Biomedicine; Neurosciences & Neurology; blood flow; Clinical Neurology

Abstract

Objective To investigate the effects of DL-3-N-butylphthalide (NBP) via intranasal delivery after ischaemic stroke in mice. Methods C57BL/6 mice were divided into three groups: sham, stroke with vehicle and stroke with NBP treatment. Ischaemic stroke was induced by permanent ligation of right middle cerebral artery with 7 min common carotid artery occlusion. NBP (100 mg/kg) or vehicle was intranasally administered at 1 hour after stroke and repeated once a day until sacrifice. Bromodeoxyuridine (BrdU) (50 mg/kg/day) was given from the third day until sacrifice. Sensorimotor function was tested during 1–21 days after stroke. Local cerebral blood flow in the ischaemic and peri-infarct regions was measured using laser Doppler flowmetry before, during and 3 days after ischaemia. Expressions of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase as well as regenerative marker BrdU in the peri-infarct region were analysed by western blotting and immunohistochemical methods. Results Compared with the vehicle group, NBP treatment significantly increased the VEGF expression in the poststroke brain. Stroke mice that received NBP showed significantly less vascular damage after stroke and more new neurons and blood vessels in the peri-infarct region at 21 days after stroke. In the adhesive removal test, the sensorimotor function of stroke mice treated with NBP performed significantly better at 1, 3 and 7 days after stroke compared with vehicle controls. Conclusion Daily intranasal NBP treatment provides protective and neurogenic/angiogenic effects in the poststroke brain, accompanied with functional improvements after a focal ischaemic stroke in mice.