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Detrimental effects of leptin on intracerebral hemorrhage via the STAT3 signal pathway.
MedLine Citation:
PMID:  23462572     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Leptin, one of the most important adipokines, is not only an energy regulator but also a regulator of innate immunity. Inflammation plays a key role in the tissue damage after intracerebral hemorrhage (ICH), and we sought to investigate whether leptin has a detrimental effect on ICH. After the injection of a high replacement dose (0.04 mg/kg) and two pharmacologic doses (4 and 8 mg/kg) of leptin, brain water contents increased significantly compared with that of control mice (P<0.05), which was confirmed when comparing the results with leptin-deficient ob/ob and wild-type (WT) mice (78.8%±0.6% versus 79.7%±0.6%, P<0.05). The number of Ox6-positive microglia/macrophages was increased in the leptin-injected group and decreased in ob/ob compared with WT mice. Among the candidate signal transducers, an increase in signal transduction and activator of transcription 3 (STAT3) levels was found after leptin injection. When we administered NSC74859, a specific inhibitor of phosphorylated STAT3 (pSTAT3), the water content became normalized. Activity of pSTAT3 was found mainly in Ox6-positive microglia/macrophages, but not in either neurons or astrocytes. We demonstrate that leptin plays a critical role in the secondary brain injury around a hematoma and is a novel mediator of the inflammation. This detrimental effect of leptin on ICH is mediated by the STAT3 signaling pathway in inflammatory cells.Journal of Cerebral Blood Flow & Metabolism advance online publication, 6 March 2013; doi:10.1038/jcbfm.2013.35.
Authors:
Chi Kyung Kim; Wi-Sun Ryu; In-Young Choi; Young-Ju Kim; Doeun Rim; Beom Joon Kim; Hyunduk Jang; Byung-Woo Yoon; Seung-Hoon Lee
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-3-06
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  -     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-3-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Laboratory for Innovative Biotechnology, Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea [2] Department of Neurology, College of Medicine and Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
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