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Original research
Vascular protection and regenerative effects of intranasal DL-3-N-butylphthalide treatment after ischaemic stroke in mice
  1. Mengyao Qu1,2,
  2. Jingjie Zhao3,
  3. Yingying Zhao1,
  4. Jinmei Sun1,
  5. Liping Liu4,5,
  6. Ling Wei2,
  7. Yongbo Zhang1
  1. 1 Neurology, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
  2. 2 Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA
  3. 3 Chinese Traditional Medicine, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
  4. 4 China National Clinical Research Center for Neurological Diseases, Beijing, China
  5. 5 Neurology, Tiantan Clinical Trial and Research Center for Stroke, Beijing, China
  1. Correspondence to Dr Yongbo Zhang; ybzhangcn{at}sina.com

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.

  • stroke
  • blood flow
  • brain
  • drug
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/svn-2020-000364

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    Footnotes

    • Contributors MQ: performed the experiments, data analysis and manuscript writing. JZ, YiZ, JS: performed the experiments and data analysis. LL: conception and experimental design. LW: conception and experimental design, data analysis and manuscript approval. YoZ: conception and financial support.

    • Funding 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).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval All animal experiments were approved by the Institutional Animal Care and Use Committee of Emory University. The protocol met the standards of the National Institute of Health.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data related to the study have been reported in the paper. Additional data are available upon request.