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 language | English |
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Pages (from-to) | 7-13 |
Number of pages | 7 |
Journal | Neuroscience Letters |
Volume | 649 |
DOIs | |
State | Published - 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