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Poloxamer-188 Can Attenuate Blood–Brain Barrier Damage to Exert Neuroprotective Effect in Mice Intracerebral Hemorrhage Model

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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.

Author Disclosure Statement

No competing financial interests exist.

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Authors and Affiliations

  1. Department of Forensic Pathology, Institute of Forensic Sciences, Ministry of Justice, 200063, Shanghai, People’s Republic of China

    Tao Wang & Yijiu Chen

  2. Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China

    Tao Wang, Xiping Chen, Zufeng Wang, Mingyang Zhang, Huanhuan Meng, Yuan Gao, Bin Luo & Luyang Tao

  3. Department of Forensic Science, Medical School of Nantong University, 226001, Nantong, China

    Mingyang Zhang

Authors
  1. Tao Wang
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  2. Xiping Chen
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  3. Zufeng Wang
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  4. Mingyang Zhang
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  5. Huanhuan Meng
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  6. Yuan Gao
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  7. Bin Luo
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  8. Luyang Tao
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  9. Yijiu Chen
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Corresponding authors

Correspondence to Luyang Tao or Yijiu Chen.

Additional information

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

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