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Molecular Medicine

, Volume 17, Issue 9–10, pp 1075–1083 | Cite as

Peripheral Administration of Human Adrenomedullin and Its Binding Protein Attenuates Stroke-Induced Apoptosis and Brain Injury in Rats

  • Wayne W. Chaung
  • Rongqian Wu
  • Youxin Ji
  • Zhimin Wang
  • Weifeng Dong
  • Cletus Cheyuo
  • Lei Qi
  • Xiaoling Qiang
  • Haichao Wang
  • Ping Wang
Research Article

Abstract

Stroke is a leading cause of death and the primary medical cause of acquired adult disability worldwide. The progressive brain injury after acute stroke is partly mediated by ischemia-elicited inflammatory responses. The vasoactive hormone adrenomedullin (AM), upregulated under various inflammatory conditions, counterbalances inflammatory responses. However, regulation of AM activity in ischemic stroke remains largely unknown. Recent studies have demonstrated the presence of a specific AM binding protein (that is, AMBP-1) in mammalian blood. AMBP-1 potentiates AM biological activities. Using a rat model of focal cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO), we found that plasma levels of AM increased significantly, whereas plasma levels of AMBP-1 decreased significantly after stroke. When given peripherally early after MCAO, exogenous human AM in combination with human AMBP-1 reduced brain infarct volume 24 and 72 h after MCAO, an effect not observed after the treatment by human AM or human AMBP-1 alone. Furthermore, treatment of human AM/AMBP-1 reduced neuron apoptosis and morphological damage, inhibited neutrophil infiltration in the brain and decreased serum levels of S100B and lactate. Thus, human AM/AMBP-1 has the ability to reduce stroke-induced brain injury in rats. AM/AMBP-1 can be developed as a novel therapeutic agent for patients with ischemic stroke.

Notes

Acknowledgments

This study was supported by NIH grants R01 HL076179, R01 GM057468 and R01 GM053008 (to P Wang).

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Copyright information

© The Feinstein Institute for Medical Research 2011
www.feinsteininstitute.org

Authors and Affiliations

  • Wayne W. Chaung
    • 1
    • 2
  • Rongqian Wu
    • 1
    • 2
  • Youxin Ji
    • 1
    • 2
  • Zhimin Wang
    • 1
    • 2
  • Weifeng Dong
    • 1
    • 2
  • Cletus Cheyuo
    • 1
    • 2
  • Lei Qi
    • 1
    • 2
  • Xiaoling Qiang
    • 1
    • 2
  • Haichao Wang
    • 1
    • 2
  • Ping Wang
    • 1
    • 2
  1. 1.Laboratory of Surgical ResearchThe Feinstein Institute for Medical ResearchManhassetUSA
  2. 2.Department of SurgeryNorth Shore University Hospital and Long Island Jewish Medical CenterManhassetUSA

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