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

Aging (Albany NY). 2020 Jun 21;12(12):11768-11780. doi: 10.18632/aging.103342. Epub 2020 Jun 21.

Abstract

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.

Keywords: L-3-n-butylphthalide; anti-inflammation; blood-brain barrier; brain edema; intracerebral hemorrhage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Apium / chemistry
  • Benzofurans / administration & dosage*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / immunology
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Brain Edema / diagnosis
  • Brain Edema / drug therapy*
  • Brain Edema / immunology
  • Brain Edema / pathology
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / immunology
  • Disease Models, Animal
  • Humans
  • Infusions, Intraventricular
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Neuroprotective Agents / administration & dosage*
  • Permeability / drug effects
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Benzofurans
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • 3-n-butylphthalide
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat