Neuroprotective Effect of Macrophage Migration Inhibitory Factor (MIF) in a Mouse Model of Ischemic Stroke

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jul 9

PMID 35805977

Authors

Ji Ae Kim

Ye Young Kim

Seung Hak Lee

Chul Jung

Mi Hee Kim

Dae Yul Kim

Affiliations

Soon will be listed here.

Abstract

The mechanism of the neuroprotective effect of the macrophage migration inhibitory factor (MIF) in vivo is unclear. We investigated whether the MIF promotes neurological recovery in an in vivo mouse model of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) surgery was performed to make ischemic stroke mouse model. Male mice were allocated to a sham vehicle, a sham MIF, a middle cerebral artery occlusion (MCAO) vehicle, and MCAO+MIF groups. Transient MCAO (tMCAO) was performed in the MCAO groups, and the vehicle and the MIF were administered via the intracerebroventricular route. We evaluated the neurological functional scale, the rotarod test, and T2-weighted magnetic resonance imaging. The expression level of the microtubule-associated protein 2 (MAP2), Bcl2, and the brain-derived neurotrophic factor (BDNF) were further measured by Western blot assay. The Garcia test was significantly higher in the MCAO+MIF group than in the MCAO+vehicle group. The MCAO+MIF group exhibited significantly better performance on the rotarod test than the MCAO+vehicle group, which further had a significantly reduced total infarct volume on T2-weighted MRI imaging than the MCAO vehicle group. Expression levels of BDNF, and MAP2 tended to be higher in the MCAO+MIF group than in the MCAO+vehicle group. The MIF exerts a neuroprotective effect in an in vivo ischemic stroke model. The MIF facilitates neurological recovery and protects brain tissue from ischemic injury, indicating a possibility of future novel therapeutic agents for stroke patients.

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References

Rudilosso S, Rodriguez-Vazquez A, Urra X, Arboix A . The Potential Impact of Neuroimaging and Translational Research on the Clinical Management of Lacunar Stroke. Int J Mol Sci. 2022; 23(3). PMC: 8835925. DOI: 10.3390/ijms23031497. View

Deacon R . Measuring motor coordination in mice. J Vis Exp. 2013; (75):e2609. PMC: 3724562. DOI: 10.3791/2609. View

Martinez A, Alcantara S, Borrell V, Del Rio J, Blasi J, Otal R . TrkB and TrkC signaling are required for maturation and synaptogenesis of hippocampal connections. J Neurosci. 1998; 18(18):7336-50. PMC: 6793248. View

Mang C, Campbell K, Ross C, Boyd L . Promoting neuroplasticity for motor rehabilitation after stroke: considering the effects of aerobic exercise and genetic variation on brain-derived neurotrophic factor. Phys Ther. 2013; 93(12):1707-16. PMC: 3870490. DOI: 10.2522/ptj.20130053. View

Wang C, Ma P, Wang Y, Yang M, Su L, Wang S . Serum level of macrophage migration inhibitory factor predicts severity and prognosis in patients with ischemic stroke. Cytokine. 2019; 115:8-12. DOI: 10.1016/j.cyto.2018.11.029. View

Kuts R, Frank D, Gruenbaum B, Grinshpun J, Melamed I, Knyazer B . A Novel Method for Assessing Cerebral Edema, Infarcted Zone and Blood-Brain Barrier Breakdown in a Single Post-stroke Rodent Brain. Front Neurosci. 2019; 13:1105. PMC: 6805703. DOI: 10.3389/fnins.2019.01105. View

Macrez R, Ali C, Toutirais O, Le Mauff B, Defer G, Dirnagl U . Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol. 2011; 10(5):471-80. DOI: 10.1016/S1474-4422(11)70066-7. View

Inacio A, Ruscher K, Leng L, Bucala R, Deierborg T . Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke. J Cereb Blood Flow Metab. 2010; 31(4):1093-106. PMC: 3070968. DOI: 10.1038/jcbfm.2010.194. View

Benedek G, Meza-Romero R, Andrew S, Leng L, Burrows G, Bourdette D . Partial MHC class II constructs inhibit MIF/CD74 binding and downstream effects. Eur J Immunol. 2013; 43(5):1309-21. PMC: 3788583. DOI: 10.1002/eji.201243162. View

10.

Leng L, Metz C, Fang Y, Xu J, Donnelly S, Baugh J . MIF signal transduction initiated by binding to CD74. J Exp Med. 2003; 197(11):1467-76. PMC: 2193907. DOI: 10.1084/jem.20030286. View

11.

Gao M, Zhang W, Liu Q, Hu J, Liu G, Du G . Pinocembrin prevents glutamate-induced apoptosis in SH-SY5Y neuronal cells via decrease of bax/bcl-2 ratio. Eur J Pharmacol. 2008; 591(1-3):73-9. DOI: 10.1016/j.ejphar.2008.06.071. View

12.

Kawabori M, Yenari M . Inflammatory responses in brain ischemia. Curr Med Chem. 2015; 22(10):1258-77. PMC: 5568039. DOI: 10.2174/0929867322666150209154036. View

13.

Garcia J, Liu K, Ho K . Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke. 1995; 26(4):636-42; discussion 643. DOI: 10.1161/01.str.26.4.636. View

14.

Czabotar P, Lessene G, Strasser A, Adams J . Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2013; 15(1):49-63. DOI: 10.1038/nrm3722. View

15.

Chang M, Park C, Rhie S, Shim W, Kim D . Early treadmill exercise increases macrophage migration inhibitory factor expression after cerebral ischemia/reperfusion. Neural Regen Res. 2019; 14(7):1230-1236. PMC: 6425847. DOI: 10.4103/1673-5374.251330. View

16.

Inacio A, Bucala R, Deierborg T . Lack of macrophage migration inhibitory factor in mice does not affect hallmarks of the inflammatory/immune response during the first week after stroke. J Neuroinflammation. 2011; 8:75. PMC: 3152909. DOI: 10.1186/1742-2094-8-75. View

17.

Shi X, Leng L, Wang T, Wang W, Du X, Li J . CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity. 2006; 25(4):595-606. PMC: 3707630. DOI: 10.1016/j.immuni.2006.08.020. View

18.

Yang L, Kong Y, Ren H, Li M, Wei C, Shi E . Upregulation of CD74 and its potential association with disease severity in subjects with ischemic stroke. Neurochem Int. 2016; 107:148-155. PMC: 5438911. DOI: 10.1016/j.neuint.2016.11.007. View

19.

Dorr A, Lerch J, Spring S, Kabani N, Henkelman R . High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice. Neuroimage. 2008; 42(1):60-9. DOI: 10.1016/j.neuroimage.2008.03.037. View

20.

Zis O, Zhang S, Dorovini-Zis K, Wang L, Song W . Hypoxia signaling regulates macrophage migration inhibitory factor (MIF) expression in stroke. Mol Neurobiol. 2014; 51(1):155-67. DOI: 10.1007/s12035-014-8727-4. View