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Brain Res. 2019 Mar 15;1707:62-73. doi: 10.1016/j.brainres.2018.11.017. Epub 2018 Nov 13.

Efficacy of leukemia inhibitory factor as a therapeutic for permanent large vessel stroke differs among aged male and female rats.

Author information

1
Department of Neurology, University of Kentucky, 741 S. Limestone, Lexington, KY 40536, United States. Electronic address: stephanie.davis@uky.edu.
2
Department of Neurology, University of Kentucky, 741 S. Limestone, Lexington, KY 40536, United States. Electronic address: lisa.collier1@uky.edu.
3
Department of Neurology, University of Kentucky, 741 S. Limestone, Lexington, KY 40536, United States. Electronic address: sarah.goodwin2@uky.edu.
4
Department of Radiology, University of Kentucky, 800 Rose St., Lexington, KY 40536, United States. Electronic address: douglas.lukins@uky.edu.
5
Spinal Cord and Brain Injury Research Center, 741 S. Limestone, Lexington, KY 40536, United States. Electronic address: david.k.powell@uky.edu.
6
Department of Neurology, University of Kentucky, 741 S. Limestone, Lexington, KY 40536, United States; Department of Neuroscience, University of Kentucky, 800 Rose St., Lexington, KY 40536, United States. Electronic address: keith.pennypacker@uky.edu.

Abstract

Preclinical studies using rodent models of stroke have had difficulty in translating their results to human patients. One possible factor behind this inability is the lack of studies utilizing aged rodents of both sexes. Previously, this lab showed that leukemia inhibitory factor (LIF) promoted recovery after stroke through antioxidant enzyme upregulation. This study examined whether LIF promotes neuroprotection in aged rats of both sexes. LIF did not reduce tissue damage in aged animals, but LIF-treated female rats showed partial motor skill recovery. The LIF receptor (LIFR) showed membrane localization in young male and aged rats of both sexes after stroke. Although LIF increased neuronal LIFR expression in vitro, it did not increase LIFR in the aged brain. Levels of LIFR protein in brain tissue were significantly downregulated between young males and aged males/females at 72 h after stroke. These results demonstrated that low LIFR expression reduces the neuroprotective efficacy of LIF in aged rodents of both sexes. Furthermore, the ability of LIF to promote motor improvement is dependent upon sex in aged rodents.

KEYWORDS:

Aging; Cytokine; Ischemia; Neuroprotection; Stroke

PMID:
30445025
DOI:
10.1016/j.brainres.2018.11.017
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