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

Stephanie M. Davis; Lisa A. Collier; Sarah Goodwin; Douglas E. Lukins; David K. Powell; Keith R. Pennypacker

doi:10.1016/j.brainres.2018.11.017

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

Stephanie M. Davis, Lisa A. Collier, Sarah Goodwin, Douglas E. Lukins, David K. Powell, Keith R. Pennypacker

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English
Pages (from-to)	62-73
Number of pages	12
Journal	Brain Research
Volume	1707
DOIs	https://doi.org/10.1016/j.brainres.2018.11.017
State	Published - Mar 15 2019

Bibliographical note

Funding Information:
The authors would like to acknowledge Dr. Justin F. Fraser for providing his expertise in cerebrovascular disease and endovascular procedures. This work was supported by the National Institute of Neurological Disorders and Stroke [Grant Number 5R01NS091146-04 , 2016] and the University of Kentucky .

Publisher Copyright:
© 2018 The Authors

Keywords

Aging
Cytokine
Ischemia
Neuroprotection
Stroke

ASJC Scopus subject areas

Neuroscience (all)
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/j.brainres.2018.11.017

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

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.",

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note = "Funding Information: The authors would like to acknowledge Dr. Justin F. Fraser for providing his expertise in cerebrovascular disease and endovascular procedures. This work was supported by the National Institute of Neurological Disorders and Stroke [Grant Number 5R01NS091146-04 , 2016] and the University of Kentucky . Publisher Copyright: {\textcopyright} 2018 The Authors",

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AU - Lukins, Douglas E.

AU - Powell, David K.

AU - Pennypacker, Keith R.

N1 - Funding Information: The authors would like to acknowledge Dr. Justin F. Fraser for providing his expertise in cerebrovascular disease and endovascular procedures. This work was supported by the National Institute of Neurological Disorders and Stroke [Grant Number 5R01NS091146-04 , 2016] and the University of Kentucky . Publisher Copyright: © 2018 The Authors

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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