Protective effects of Ephedra sinica extract on blood-brain barrier integrity and neurological function correlate with complement C3 reduction after subarachnoid hemorrhage in rats

Shilun Zuo, Wenyan Li, Qiang Li, Hengli Zhao, Jun Tang, Qianwei Chen, Xin Liu, John H. Zhang, Yujie Chen, Hua Feng

Research output: Contribution to journalArticlepeer-review

Abstract

Early brain injury, which is associated with brain cell death, blood-brain barrier disruption, brain edema, and other pathophysiological events, is thought to be the main target in the prevention of poor outcomes after subarachnoid hemorrhage (SAH). Emerging evidences indicates that complement system, especially complement C3 is detrimental to neurological outcomes of SAH patients. Recently, Ephedra sinica extract was extracted and purified, which exhibits ability to block the activity of the classical and alternative pathways of complement, and improve neurological outcomes after spinal cord injury and ischemic brain injury. However, it is still unclear whether Ephedra sinica extract could attenuate early brain injury after SAH. In the present study, a standard endovascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. Ephedra sinica extract (15. mg/kg) was orally administrated daily and evaluated for effects on modified Garcia score, brain water content, Evans blue extravasation and fluorescence, cortex cell death by TUNEL staining, and the expressions of complement C3/C3b, activated C3, sonic hedgehog, osteopontin and matrix metalloproteinase-9 by western bolt and immunofluorescence staining. We founded that the Ephedra sinica extract alleviated the blood-brain barrier disruption and brain edema, eventually improved neurological functions after SAH in rats. These neuroprotective effects was associated with the inhibition of complement C3, possibly via upregulating sonic hedgehog and osteopontin signal, and reducing the expressions of matrix metalloproteinase-9. Taking together, these observations suggested complement C3 inhibition by the Ephedra sinica extract may be a protective factor against early brain injury after SAH.

Original languageEnglish
Pages (from-to)216-222
Number of pages7
JournalNeuroscience Letters
Volume609
DOIs
StatePublished - Nov 16 2015

ASJC Scopus Subject Areas

  • General Neuroscience

Keywords

  • Blood-brain barrier
  • Complement C3
  • Early brain injury
  • Ephedra sinica
  • Subarachnoid hemorrhage
  • Matrix Metalloproteinase 9/metabolism
  • Hedgehog Proteins/metabolism
  • Male
  • Brain Edema/drug therapy
  • Permeability
  • Neuroprotective Agents/pharmacology
  • Rats, Sprague-Dawley
  • Osteopontin/metabolism
  • Animals
  • Blood-Brain Barrier/drug effects
  • Complement C3/metabolism
  • Ephedra sinica/chemistry
  • Cell Death
  • Cerebral Cortex/drug effects
  • Plant Extracts/pharmacology
  • Subarachnoid Hemorrhage/drug therapy

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