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Dexamethasone inhibits ICAM-1 and MMP-9 expression and reduces brain edema in intracerebral hemorrhagic rats

  • Experimental research
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Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

The molecular mechanism of hemorrhagic stroke is unclear, and the identification of therapeutic agents for attenuating post-stroke brain damage remains an unresolved challenge. Dexamethasone (DEX) is used clinically to treat spinal cord injury and brain tumor patients by reducing edema formation, but has produced conflicting results in stroke management.

Methods

In this study, intracerebral hemorrhage (ICH) was induced in rats by intracranial stereotactic injection of collagenase into the caudate nucleus. DEX was given immediately and 3 days after ICH. The expression of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), nuclear factor (NF)-κB, and IκB were analyzed by Western blotting, and perihematomal edema formation was evaluated by magnetic resonance imaging.

Results

The results showed that ICH caused an increase of ICAM-1 and MMP-9 expression from 4 h to 7 days, which was inhibited following the administration of DEX. The perihematomal edema volume in ICH rats was high, with two peak periods at 12 h and 3 days, which was also reduced in DEX-treated groups. Furthermore, the administration of DEX not only maintained IκB in cytoplasm, but also decreased NF-κB elevation in the nucleus at 3 and 5 days in ICH rats.

Conclusions

In conclusion, these data show that DEX successfully reduced post-stroke brain edema by decreasing MMP-9 and ICAM-1 levels, partially through the IκB/NF-κB signaling pathway. The timing of DEX administration in relation to the onset of brain injury may be critical.

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Acknowledgments

This work was supported by grant NSC 96-2314-B-182A-013 from the National Science Council and grant CMRPG 690501 from the Chang Gung Medical Research Council, Taiwan, ROC.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Chang Gung Memorial Hospital at Chia-Yi, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan

    Jen-Tsung Yang & I-Neng Lee

  2. Department of Neurology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan

    Tsong-Hai Lee

  3. Molecular Medicine Research Center, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan

    I-Neng Lee

  4. Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan

    Chiu-Yen Chung

  5. Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

    Chia-Hui Kuo

  6. Department of Radiology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan

    Hsu-Huei Weng

  7. Department of Neurosurgery, Chang Gung Memorial Hospital, 6, sec. West, Chia Pu Rd., Pu Tz City, Chia-Yi, Taiwan

    Jen-Tsung Yang

Authors
  1. Jen-Tsung Yang
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  2. Tsong-Hai Lee
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Corresponding author

Correspondence to Jen-Tsung Yang.

Additional information

Comment

This is an elegantly performed experimental investigation, utilising state-of-the art methodologies to assess the neuroprotective effect of DEX in a well-established rat model of ICH. The results are sound and convincingly discussed. Differently from blood-injection techniques, the collagenase method produces ICH mimicking a more human-like evolving bleeding. There is a more pronounced interindividual variability of size and time course of the resulting ICHs. In this respect, including MRI images used for edema assessment is a useful adjunct, adding value to this paper. The dosing and time course of DEX administration are critical issues. Expression of ICAM-1 was significantly affected by DEX at all experimental time points, expression of MPP-9 only at the very early and very late stages of ICH production. Edema formation was reduced at 12 h and 3–5 days thereafter. It could be that a different dose-response curve could be obtained wiht another dosing. In conclusion, this is an interesting investigation proposing the reassessment of the pharmacodynamics of an old and controversial drug in a modern and sophisticated experimental setting. Translation of these results in the clinical field is still far away.

Domenico d'Avella

Padova, Italy

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Yang, JT., Lee, TH., Lee, IN. et al. Dexamethasone inhibits ICAM-1 and MMP-9 expression and reduces brain edema in intracerebral hemorrhagic rats. Acta Neurochir 153, 2197–2203 (2011). https://doi.org/10.1007/s00701-011-1122-2

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  • DOI: https://doi.org/10.1007/s00701-011-1122-2

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