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Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage

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Abstract

Intracerebral hemorrhage (ICH) leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage (ICH). The results showed that fingolimod decreased the numbers of circulating CD4+ T, CD8+ T, CD19+ B, NK, and NKT cells and they recovered quickly after the drug was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.

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Authors and Affiliations

  1. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Yu-Jing Li, Guo-Qiang Chang, Yuanchu Liu, Ye Gong, Chunsheng Yang, Fu-Dong Shi, Ying Fu & Yaping Yan

  2. Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an, 710062, China

    Yuanchu Liu & Ye Gong

  3. Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, 85013, USA

    Kristofer Wood & Fu-Dong Shi

Authors
  1. Yu-Jing Li
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  2. Guo-Qiang Chang
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  3. Yuanchu Liu
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  4. Ye Gong
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  5. Chunsheng Yang
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  6. Kristofer Wood
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  7. Fu-Dong Shi
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  8. Ying Fu
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  9. Yaping Yan
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Correspondence to Ying Fu or Yaping Yan.

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Li, YJ., Chang, GQ., Liu, Y. et al. Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage. Neurosci. Bull. 31, 755–762 (2015). https://doi.org/10.1007/s12264-015-1532-2

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  • DOI: https://doi.org/10.1007/s12264-015-1532-2

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