Cyclosporine A alleviated matrix metalloproteinase 9 associated blood-brain barrier disruption after subarachnoid hemorrhage in mice

Pengyu Pan, Xuan Zhang, Qiang Li, Hengli Zhao, Jie Qu, John H. Zhang, Xin Liu, Hua Feng, Yujie Chen

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to investigate whether Cyclosporine A (CsA) attenuates early brain injury by alleviating matrix metalloproteinase 9 (MMP-9) associated blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in C57B6J mice. Dosages of 5 mg/kg, 10 mg/kg and 15 mg/kg CsA were evaluated for effects on neurological score, brain water content, Evans blue extravasation and fluorescence, P-p65, MMP-9 and BBB components’ alterations after SAH. We found that CsA 15 mg/kg is effective in attenuating BBB disruption, lowering edema, and improving neurological outcomes. In addition, Collagen IV, ZO-1, Occludin and Claudin 5 expressions in ipsilateral/left hemisphere were downregulated after SAH, but increased after CsA treatment. Our results suggest that CsA exert a neuroprotective role in SAH pathophysiology, possibly by alleviating MMP-9 associated BBB disruption.

Original languageEnglish
Pages (from-to)7-13
Number of pages7
JournalNeuroscience Letters
Volume649
DOIs
StatePublished - May 10 2017

ASJC Scopus Subject Areas

  • General Neuroscience

Keywords

  • Blood-brain barrier
  • Cyclosporine A
  • Early brain injury
  • Matrix metalloproteinase 9
  • Subarachnoid hemorrhage
  • Neuroprotective Agents/administration & dosage
  • Occludin/metabolism
  • Matrix Metalloproteinase 9/metabolism
  • Mice, Inbred C57BL
  • Male
  • Subarachnoid Hemorrhage/metabolism
  • Claudin-5/metabolism
  • Animals
  • Zonula Occludens-1 Protein/metabolism
  • Blood-Brain Barrier/drug effects
  • Brain Edema/prevention & control
  • Cyclosporine/administration & dosage

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