Research Paper Volume 12, Issue 12 pp 11768—11780

L-3-n-butylphthalide attenuates inflammation response and brain edema in rat intracerebral hemorrhage model

Zhou Zeng1, , Xiyu Gong1, , Zhiping Hu1, ,

  • 1 Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China

Received: January 11, 2020       Accepted: May 18, 2020       Published: June 21, 2020
How to Cite

Copyright © 2020 Zeng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


L-3-n-butylphthalide(NBP), a compound found in Apium graveolens Linn seed extracts, has a therapeutic effect on acute ischemic stroke. The pathological inflammatory pathways and consequent brain edema in intracerebral hemorrhage (ICH) share some similar characteristics with ischemic stroke. We hypothesized that NBP has anti-inflammatory and therapeutic effects on rats with ICH. ICH was induced by an infusion of bacterial collagenase type IV into the unilateral striatum of anesthetized rats. The therapeutic effect of NBP was measured by assessing neurological function, brain water content, blood-brain barrier permeability, and expression of tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) around the hematoma 48 hours after surgery. Magnetic resonance imaging was performed 4 and 48 hours after ICH induction, and ICH-induced injured area volumes were measured using T2-weighted images. The NBP treatment group performed better in the neurological function test than the vehicle group. Moreover, in comparison with the vehicle group, NBP group showed a lower expanded hematoma volume, brain water content, blood-brain barrier permeability, and TNF-α/ MMP-9 expression level. Our results indicate that NBP attenuates inflammation and brain edema in rat ICH model. Therefore, our findings also provide a potential therapeutic strategy for the treatment of ICH with NBP.


NBP: L-3-n-butylphthalide; ICH: intracerebral hemorrhage; TNF-α: tumor necrosis factor-alpha; MMP-9: matrix metalloproteinase-9; BBB: blood-brain barrier; BID: twice-daily; i.p.: intraperitoneal; MRI: magnetic resonance imaging; CNS: central nervous system; ROS: reactive oxygen species; SOD: Super oxide dismutase; MDA: Malondialdehyde.