Adiponectin protects against cerebral ischemia-reperfusion injury through anti-inflammatory action.

Abstract

Adiponectin (APN), a circulating adipose-derived hormone regulating inflammation and energy metabolism, has beneficial actions on cardio- and cerebrovascular disorders. Hypoadiponectinemia is associated with ischemic cerebrovascular disease, however, little is known about the cerebroprotective action of APN as well as its molecular mechanisms. In the present study, the role of APN in the pathogenesis of acute cerebral injury was investigated. Rats were divided into three groups: (i) a sham operation group; (ii) an ischemia/reperfusion (I/R) group, rats were subjected to 1 h middle cerebral artery occlusion followed by 23 h reperfusion (I/R); (iii) a APN-treated group, two bolus of 5 microg APN was administered through jugular vein before and after operation. I/R resulted in obvious cerebral infarct size, neurological deficits, and increased expression of endogenous immunoglobin G and matrix metalloproteinase 9, which can be significantly diminished by administration of APN. We also found that APN can significantly inhibited cerebral expression of myeloperoxidase, a distinct indicator of inflammatory cell infiltration, and inflammatory cytokines, interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-8 in response to I/R, suggesting that APN exerts potent anti-inflammatory actions. Furthermore, nuclear factor (NF)-kappaB (p65), a critical transcription factor involved in inflammatory reactions, was observed predominantly located in the nucleus after I/R, whereas APN can obviously inhibit its translocation from cytoplasm into the nucleus. Results of this study demonstrate that APN exerts a potent cerebroprotective function through its anti-inflammatory action, and NF-kappaB (p65) is a key component in this process. APN might be potential molecular targets for ischemic stroke therapy.

• Authors: Bi Chen, Wen-Qiang Liao, Ning Xu, Hao Xu, Jian-Yan Wen, Chang-An Yu, Xiang-Yuan Liu, Chang-Ling Li, Shu-Min Zhao, William Campbell
• Journal: Brain research (Brain Res) Vol. 1273 Pg. 129-37 (Jun 01 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19362080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Anti-Inflammatory Agents
• Cytokines
• Immunoglobulin G
• Neuroprotective Agents
• Transcription Factor RelA
• Peroxidase
• Matrix Metalloproteinase 9

Topics

• Active Transport, Cell Nucleus (drug effects, physiology)
• Adiponectin (metabolism, pharmacology)
• Animals
• Anti-Inflammatory Agents (metabolism, pharmacology)
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Cytokines (drug effects, metabolism)
• Cytoprotection (drug effects, physiology)
• Disease Models, Animal
• Encephalitis (drug therapy, metabolism, physiopathology)
• Immunoglobulin G (drug effects, metabolism)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, physiopathology)
• Injections, Intravenous
• Male
• Matrix Metalloproteinase 9 (drug effects, metabolism)
• Neuroprotective Agents (metabolism, pharmacology)
• Peroxidase (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism, physiopathology)
• Transcription Factor RelA (drug effects, metabolism)