Detrimental effects of leptin on intracerebral hemorrhage via the STAT3 signal pathway

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)944-953
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume33
Issue number6
DOIs
Publication statusPublished - 2013 Jun 1
Externally publishedYes

Fingerprint

Cerebral Hemorrhage
Leptin
Signal Transduction
Microglia
NSC 74859
Macrophages
Inflammation Mediators
Injections
Adipokines
Water
Transducers
Innate Immunity
Astrocytes
Hematoma
Brain Injuries
Inflammation
Neurons
Brain

Keywords

  • Acute stroke
  • Adipokine
  • Brain edema
  • Inflammation
  • Intracerebral hemorrhage
  • Leptin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Detrimental effects of leptin on intracerebral hemorrhage via the STAT3 signal pathway. / Kim, Chi Kyung; Ryu, Wi Sun; Choi, In Young; Kim, Young Ju; Rim, Doeun; Kim, Beom Joon; Jang, Hyunduk; Yoon, Byung Woo; Lee, Seung Hoon.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 33, No. 6, 01.06.2013, p. 944-953.

Research output: Contribution to journalArticle

Kim, Chi Kyung ; Ryu, Wi Sun ; Choi, In Young ; Kim, Young Ju ; Rim, Doeun ; Kim, Beom Joon ; Jang, Hyunduk ; Yoon, Byung Woo ; Lee, Seung Hoon. / Detrimental effects of leptin on intracerebral hemorrhage via the STAT3 signal pathway. In: Journal of Cerebral Blood Flow and Metabolism. 2013 ; Vol. 33, No. 6. pp. 944-953.
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