Abstract
Blood–brain barrier (BBB) disruption and brain edema formation play important roles in the secondary neuronal death and neurological dysfunction induced by intracerebral hemorrhage (ICH). Poloxamer 188 (P188), a multiblock copolymer surfactant, has been shown to be capable of sealing damaged cell membranes and decrease neuronal cell death. In this study, we explored whether P188 had a protective effect against ICH and its underlying mechanisms. Male ICR mice were subjected to infusion of type IV collagenase (to induce ICH) of saline (for shams) into the left striatum. The results showed that P188-12 mg post-treatment by tail intravenous injection significantly ameliorated the neurological symptoms and brain edema, attenuated BBB permeability, and decreased cell insults and injury volume at 24 and 72 h after ICH. Furthermore, P188 maintained the protein levels of tight junction (TJ) proteins including claudin-5, occludin, and zonula occludens-1, and reversed the increases of nuclear factor-kappaB (NF-κB), matrix metalloproteinase (MMP)-2, and MMP-9 protein expression at 72 h post ICH. Immunofluorescence showed P188 treatment rearranged the structure of TJ proteins in a continuous and linear pattern. Therefore, the present study concludes that P188 can protect against ICH, and the protective effect was associated with preventing BBB disruption through NF-κB-MMPs-mediated TJ proteins degradation.
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Abbreviations
- ICH:
-
Intracerebral hemorrhage
- BBB:
-
Blood–brain barrier
- P188:
-
Poloxamer 188
- PI:
-
Propidium iodide
- TJ:
-
Tight junction
- MMP:
-
Matrix metalloproteinase
- ZO:
-
Zonula occludens
- BCA:
-
Bicinchoninic acid
- SDS:
-
Sodium dodecyl sulfate
- PVDF:
-
Hybond-polyvinylidene difluoride
- TBST:
-
Tris-buffered saline with tween
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Acknowledgments
This study was supported by grants (nos. 81172911, 81271379, 81273338, 81301039, and 81373251) from the National Natural Science Foundation of China, Key Projects in the National Science & Technology Pillar Program during the Twelfth Five-Year Plan Period (no. 2012BAK16B02), Shanghai Postdoctoral Scientific Program (no. 14R21423000), and the Science and Technology Development Project of Suzhou (no. SZP201304), and conceived and designed the experiments: WT, CX, TL, and CY; performed the experiments: WT and WZ; analyzed the data: WT, ZM, MH, and TL; contributed reagents/materials/analysis tools: CX, GY, LB, and CY; and wrote the manuscript: WT, TL, and CY.
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Tao Wang and Xiping Chen contributed equally to this work.
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Wang, T., Chen, X., Wang, Z. et al. Poloxamer-188 Can Attenuate Blood–Brain Barrier Damage to Exert Neuroprotective Effect in Mice Intracerebral Hemorrhage Model. J Mol Neurosci 55, 240–250 (2015). https://doi.org/10.1007/s12031-014-0313-8
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DOI: https://doi.org/10.1007/s12031-014-0313-8