Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in Ischemic Stroke
Journal
Scientific Reports
Journal Volume
8
Journal Issue
1
Pages
743
Date Issued
2018
Author(s)
Abstract
Ischemic stroke is a devastating disease with limited therapeutic options. It is very urgent to find a new target for drug development. Here we found that the blood level of MIF in ischemic stroke patients is upregulated. To figure out the pathological role of MIF in ischemic stroke, both in vitro and in vivo studies were conducted. For in vitro studies, primary cortical neuron cultures and adult rat brain endothelial cells (ARBECs) were subjected to oxygen-glucose deprivation (OGD)/reoxygenation. Middle cerebral artery occlusion (MCAo) rodent models were used for in vivo studies. The results show that MIF exerts no direct neuronal toxicity in primary culture but disrupts tight junction in ARBECs. Furthermore, administration of MIF following MCAo shows the deleterious influence on stroke-induced injury by destroying the tight junction of blood-brain barrier and increasing the infarct size. In contrast, administration of MIF antagonist ISO-1 has the profound neuroprotective effect. Our results demonstrate that MIF might be a good drug target for the therapy of stroke. ? 2018 The Author(s).
Other Subjects
isomerase; macrophage migration inhibition factor; Mif protein, rat; animal; blood brain barrier; cell culture; cerebrovascular accident; disease model; endothelium cell; human; metabolism; nerve cell; pathology; permeability; rat; Animals; Blood-Brain Barrier; Cells, Cultured; Disease Models, Animal; Endothelial Cells; Humans; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Neurons; Permeability; Rats; Stroke
Type
journal article