Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model

Macrophage migration inhibitory factor (MIF) exerts neuroprotective effects against cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis and inducing the expression of brain-derived neurotrophic factor (BDNF). However, the optimal administration conditions of MIF are currently unkno...

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Main Authors: Chul Jung, Mi Hee Kim, Ye Yeong Kim, Ji Ae Kim, Eun Jae Ko, Seung Hak Lee, Dae Yul Kim
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/11/2/280
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author Chul Jung
Mi Hee Kim
Ye Yeong Kim
Ji Ae Kim
Eun Jae Ko
Seung Hak Lee
Dae Yul Kim
author_facet Chul Jung
Mi Hee Kim
Ye Yeong Kim
Ji Ae Kim
Eun Jae Ko
Seung Hak Lee
Dae Yul Kim
author_sort Chul Jung
collection DOAJ
description Macrophage migration inhibitory factor (MIF) exerts neuroprotective effects against cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis and inducing the expression of brain-derived neurotrophic factor (BDNF). However, the optimal administration conditions of MIF are currently unknown. Here, we aimed to identify these conditions in an in vitro model. To determine the optimal concentration of MIF, human neuroblastoma cells were assigned to one of seven groups: control, oxygen and glucose deprivation/reperfusion (OGD/R), and OGD/R with different concentrations (1, 10, 30, 60, and 100 ng/mL) of MIF. Six groups were studied to investigate the optimal administration time: control, OGD/R, and OGD/R with MIF administered at different times (pre-OGD, OGD-treat, post-OGD, and whole-processing). Water-soluble tetrazolium salt-1 assay, Western blot analysis, and immunocytochemistry were used to analyze cell viability and protein expression. We found that 60 ng/mL was the optimal concentration of MIF. However, the effects of administration time were not significant; MIF elicited similar neuroprotective effects regardless of administration time. These findings correlated with the expression of BDNF and apoptosis-related proteins. This study provides detailed information on MIF administration, which offers a foundation for future in vivo studies and translation into novel therapeutic strategies for ischemic stroke.
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spelling doaj.art-f7fcba5b5c5041b1bdd739b3b437e6722023-12-11T18:10:15ZengMDPI AGBrain Sciences2076-34252021-02-0111228010.3390/brainsci11020280Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke ModelChul Jung0Mi Hee Kim1Ye Yeong Kim2Ji Ae Kim3Eun Jae Ko4Seung Hak Lee5Dae Yul Kim6Asan Medical Center, Department of Rehabilitation Medicine, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan Medical Center, Department of Rehabilitation Medicine, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan Medical Center, Department of Rehabilitation Medicine, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan Medical Center, Department of Rehabilitation Medicine, University of Ulsan College of Medicine, Seoul 05505, KoreaAsan Medical Center, Department of Rehabilitation Medicine, University of Ulsan College of Medicine, Seoul 05505, KoreaMacrophage migration inhibitory factor (MIF) exerts neuroprotective effects against cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis and inducing the expression of brain-derived neurotrophic factor (BDNF). However, the optimal administration conditions of MIF are currently unknown. Here, we aimed to identify these conditions in an in vitro model. To determine the optimal concentration of MIF, human neuroblastoma cells were assigned to one of seven groups: control, oxygen and glucose deprivation/reperfusion (OGD/R), and OGD/R with different concentrations (1, 10, 30, 60, and 100 ng/mL) of MIF. Six groups were studied to investigate the optimal administration time: control, OGD/R, and OGD/R with MIF administered at different times (pre-OGD, OGD-treat, post-OGD, and whole-processing). Water-soluble tetrazolium salt-1 assay, Western blot analysis, and immunocytochemistry were used to analyze cell viability and protein expression. We found that 60 ng/mL was the optimal concentration of MIF. However, the effects of administration time were not significant; MIF elicited similar neuroprotective effects regardless of administration time. These findings correlated with the expression of BDNF and apoptosis-related proteins. This study provides detailed information on MIF administration, which offers a foundation for future in vivo studies and translation into novel therapeutic strategies for ischemic stroke.https://www.mdpi.com/2076-3425/11/2/280macrophage migration inhibitory factorneuroprotectionbrain-derived neurotrophic factorapoptosisischemic stroke
spellingShingle Chul Jung
Mi Hee Kim
Ye Yeong Kim
Ji Ae Kim
Eun Jae Ko
Seung Hak Lee
Dae Yul Kim
Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model
Brain Sciences
macrophage migration inhibitory factor
neuroprotection
brain-derived neurotrophic factor
apoptosis
ischemic stroke
title Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model
title_full Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model
title_fullStr Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model
title_full_unstemmed Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model
title_short Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model
title_sort determining the optimal administration conditions under which mif exerts neuroprotective effects by inducing bdnf expression and inhibiting apoptosis in an in vitro stroke model
topic macrophage migration inhibitory factor
neuroprotection
brain-derived neurotrophic factor
apoptosis
ischemic stroke
url https://www.mdpi.com/2076-3425/11/2/280
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