title: Detrimental effects of leptin on intracerebral hemorrhage via the STAT3 signal pathway.
abstract: 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.
authors: Laboratory for Innovative Biotechnology, Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
authors: Chi Kyung
authors: CK
authors: Kim
authors: Wi-Sun
authors: WS
authors: Ryu
authors: In-Young
authors: IY
authors: Choi
authors: Young-Ju
authors: YJ
authors: Kim
authors: Doeun
authors: D
authors: Rim
authors: Beom Joon
authors: BJ
authors: Kim
authors: Hyunduk
authors: H
authors: Jang
authors: Byung-Woo
authors: BW
authors: Yoon
authors: Seung-Hoon
authors: SH
authors: Lee
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001929:Brain Edema / Q000276:immunology; D002543:Cerebral Hemorrhage / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D020738:Leptin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000008:administration & dosage / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D014867:Water / Q000032:analysis
chemical_list: D020738:Leptin; D050796:STAT3 Transcription Factor; D014867:Water