Table 5.

The role of MIF in stroke.

Authors	Study design	Results
Wang et al. 2009 [55]	AIS patients: mean age (years) = 68.61, gender (m/f) = 61/41 Control: mean age (years) = 68.12, gender (m/f) = 32/25 12-week-old male and female Wistar rats subjected to MCAO	MIF protein and mRNA were increased in stroke patients and rat models, and positively correlated to the disease severity.
Zis et al. 2015 [56]	Human ischemic brain HEK293 cells Primary cortical neurons of rat brain subjected to OGD	MIF was increased in human ischemic brain. MIF promoter activity was upregulated under hypoxia. MIF overexpression reduced OGD-induced cell death.
Yang et al. 2017 [60]	AIS patients: mean age (years) = 66.60, gender (m/f) = 13/7 Control: mean age (years) = 63.71, gender (m/f) = 8/6	MIF and CD74 levels were increased in PBMCs of ischemic stroke patients.
Li et al. 2017 [57]	First episode of AIS patients within 24 h of symptom onset: mean age (years) = 65.35, gender (m/f) = 83/63 Control: mean age (years) = 66.33, gender (m/f) = 26/19	MIF serum levels were increased and positively associated with infarct volume, and NIHSS score.
Liu et al. 2018 [59]	AIS patients: n=39 Control: n=14 13-15-week-old male Wistar rats and SHRs subjected to MCAO ARBECs subjected to OGD	MIF blood levels were upregulated both in stroke patients and MCAO rats. MIF showed a deleterious influence on stroke by destroying the tight junction of blood-brain barrier both in vitro and in vivo. ISO-1 showed a neuroprotective effect in stroke.
Xu et al. 2018 [42]	AIS patients: mean age (years) = 64, gender (m/f) = 181/152	Elevated plasma levels of MIF were associated with an increased risk of post-stroke depression.
Wang et al. 2019 [58]	AIS patients: mean age (years) = 61, gender (m/f) = 155/134	MIF serum levels were upregulated and independently related to clinical severity and poor outcome.
Inácio et al. 2011 [69]	8-36-week-old WT and MIF−/− male mice subjected to MCAO	MIF deletion did not affect the inflammatory/immune response during the first week after the stroke.
Zhang et al. 2014 [61]	10-12-week-old WT and MIF−/− male mice subjected to transient distal MCAl Cell of HEK293, BV-2 and human neuroblastoma N2A	MIF knockout resulted in caspase-3 activation, neuronal loss, and increased infarct development via NF-kB signaling. Overexpression of MIF reduced the cell death induced by H2O2.
Turtzo et al. 2013 [70]	8-10-week-old male and female WT and MIF−/− mice subjected to MCAO	Female MIF KO mice showed larger strokes compared to WT females as well as in ovariectomized female mice.
Bae et al. 2020 [62]	SH-SY5Y cells subjected to OGD/R MIF recombinant and ISO-1	MIF increased the levels of BDNF, Bcl2, and MAP2, and decreased the levels of Caspase-3 and Bax under OGD, which could be reversed by ISO-1.
Chang et al. 2019 [64]	8-week-old male Sprague-Dawley rats subjected to MCAO	Exercise could improve motor dysfunction and neuronal recovery after I/R in rats by increasing the levels of MIF and BDNF.
Kim et al. 2022 [63]	10-12-week-old adult male c57/BL6 mice subjected to MCAO	ICV of MIF exhibited better performance on the rotarod test and lower total infarct volume by increasing the levels of BDNF and MAP2.
Jung et al. 2021 [65]	SH-SY5Y cells subjected to OGD/R	60 ng/mL of MIF showed the best protective effect but have no significant difference in administration time.
Hu et al. 2022 [66]	2-3-month-old male HDAC6 mutant mice and MIF K78Q mice subjected to photothrombotic ischemia	HDAC6 inhibitor or aspirin protected cortical neuronal death by promoting MIF acetylation on the K78 residue.
Li et al. 2020 [67]	Male rats subjected to MCAO SH-SY5Y cells subjected to OGD	Baicalein decreased cerebral infarct volume and neurological scores by inhibiting MIF.
Li et al. 2016 [68]	Male rats subjected to MCAO RBMECs subjected to OGD/R	Protective effect of miR-493 inhibition in angiogenesis was attenuated by knocking down MIF after MCAO.
Inácio et al. 2011 [71]	8-36-week-old WT and MIF−/− male mice subjected to MCAO Primary neuronal cells subjected to OGD	MIF-KO mice decreased infarct volume and promoted recovery of neurologic function after MCAO.