Activation of cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 attenuates ischemic brain injury in rats

Shigeaki Suzuki, Toru Yamashita, Kortaro Tanaka, Hidenori Hattori, Kazunobu Sawamoto, Hideyuki Okano, Norihiro Suzuki

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 is known to exert a neurotrophic action in the central nervous system, although the role of this signaling in cerebral ischemia remains unknown. We examined the effect of intracerebral injection of LIF after focal cerebral ischemia in rats. The animals underwent a sham operation (sham group) or middle cerebral artery occlusion (MCAO) followed by direct injection of either vehicle (phosphate-buffered saline, the PBS group) or recombinant LIF (10 ng in the low-LIF group and 100 ng in the high-LIF group) into the cerebral cortex adjacent to the inner boundary zone of the infarct area, and neurologic and histologic evaluations were conducted 24 h later. Expression of LIFR, gp130, and phosphorylated Stat3, Akt, and ERK1/2 was investigated by Western blot analysis and immunohistochemistry. The neurologic deficits and ischemic damage were significantly less severe in the high-LIF group than in the PBS group and the low-LIF group. Leukemia inhibitory factor receptor and gp130 were expressed in neurons, and the ischemic damage of these proteins was rescued in the high-LIF group. Early induction of phosphorylated Stat3 was significantly detected on the ischemic side in the high-LIF group after LIF injection. Exogenous LIF attenuates ischemic brain injury by activating cytokine signaling through LIFR/gp130.

Original languageEnglish
Pages (from-to)685-693
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume25
Issue number6
DOIs
Publication statusPublished - 2005 Jun

Fingerprint

OSM-LIF Receptors
Brain Injuries
Cytokines
Brain Ischemia
Injections
Middle Cerebral Artery Infarction
Neurologic Manifestations
Cerebral Cortex
Nervous System
Central Nervous System
Western Blotting
Immunohistochemistry
Phosphates
Neurons
Proteins

Keywords

  • Gp130
  • Ischemia
  • Leukemia inhibitory factor
  • Neuroprotection
  • Stat3

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Activation of cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 attenuates ischemic brain injury in rats. / Suzuki, Shigeaki; Yamashita, Toru; Tanaka, Kortaro; Hattori, Hidenori; Sawamoto, Kazunobu; Okano, Hideyuki; Suzuki, Norihiro.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 25, No. 6, 06.2005, p. 685-693.

Research output: Contribution to journalArticle

Suzuki, Shigeaki ; Yamashita, Toru ; Tanaka, Kortaro ; Hattori, Hidenori ; Sawamoto, Kazunobu ; Okano, Hideyuki ; Suzuki, Norihiro. / Activation of cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 attenuates ischemic brain injury in rats. In: Journal of Cerebral Blood Flow and Metabolism. 2005 ; Vol. 25, No. 6. pp. 685-693.
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