Leukemia Inhibitory Factor Protects Neurons from Ischemic Damage via Upregulation of Superoxide Dismutase 3

Stephanie M. Davis, Lisa A. Collier, Christopher C. Leonardo, Hilary A. Seifert, Craig T. Ajmo, Keith R. Pennypacker

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Leukemia inhibitory factor (LIF) has been shown to protect oligodendrocytes from ischemia by upregulating endogenous antioxidants. The goal of this study was to determine whether LIF protects neurons during stroke by upregulating superoxide dismutase 3 (SOD3). Animals were administered phosphate-buffered saline (PBS) or 125 μg/kg LIF at 6, 24, and 48 h after middle cerebral artery occlusion or sham surgery. Neurons were isolated from rat pups on embryonic day 18 and used between 7 and 15 days in culture. Cells were treated with LIF and/or 10 μM Akt inhibitor IV with PBS and 0.1 % DMSO acting as vehicle controls. Neurons transfected with scrambled or SOD3 small interfering RNA (siRNA) were subjected to 24-h ischemia after PBS or LIF treatment. LIF significantly increased superoxide dismutase activity and SOD3 expression in ipsilateral brain tissue compared to PBS. Following 24-h ischemia, LIF reduced cell death and increased SOD3 messenger RNA (mRNA) in vitro compared to PBS. Adding Akt inhibitor IV with LIF counteracted the decrease in cell death. Partially silencing the expression of SOD3 using siRNA prior to LIF treatment counteracted the protective effect of LIF-alone PBS treatment. These results indicate that LIF protects neurons in vivo and in vitro via upregulation of SOD3.

Original languageEnglish
Pages (from-to)608-622
Number of pages15
JournalMolecular Neurobiology
Issue number1
StatePublished - Jan 1 2017

Bibliographical note

Funding Information:
This laboratory would like to acknowledge Dr. Chris Katnik and Dr. Byeong “Jake” Cha for technical assistance regarding neuronal culture and tissue imaging, Dr. Jerome Breslin for the use of Lonza Nucleofection equipment, and the USF College of Medicine vivarium staff for their dedication to quality animal care. Funding was provided by grants from the National Institute of Neurological Disorders and Stroke (1R56NS091146-01 and 5R21NS078517-02).

Publisher Copyright:
© 2016, The Author(s).


  • Neuroprotection
  • Oxidative stress
  • Stroke
  • Superoxide dismutase

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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