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Brain Res. 2009 Jun 1;1273:129-37. doi: 10.1016/j.brainres.2009.04.002. Epub 2009 Apr 9.

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

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1
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, China.

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.

PMID:
19362080
DOI:
10.1016/j.brainres.2009.04.002
[Indexed for MEDLINE]
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