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Updated: Nov 9, 2025
Modeling Stroke in Mice - Middle Cerebral Artery Occlusion with the Filament Model
Published on: January 6, 2011
Hypothermia Protects Mice Against Ischemic Stroke by Modulating Macrophage Polarization Through Upregulation of
Xinyuan Yu1, Yanping Feng1, Renzhong Liu1
1Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People's Republic of China.
Background:
Therapeutic hypothermia (TH) has been proven to be protective in ischemic stroke (IS) due to its anti-inflammatory capacity. Recently, the interferon regulatory factor 4 (IRF4) has been characterized as a central regulator of neuroinflammation in IS. Here we aim to determine whether IFR4 contributes to the neuroprotective effects of TH in IS.
Methods:
In the present study, IRF4 knockout (IRF4-/-) and wild-type (IRF4+/+) mice were treated with or without TH after IS. Cerebral IRF4 expression, the production of pro-inflammatory and anti-inflammatory cytokines and macrophage polarization were determined at 8 hours after reperfusion. In addition, cerebral infarct volume and neurological function were evaluated at 7 days after IS.
Results:
TH attenuates IS together with enhanced IRF4 expression as well as reduced production of pro-inflammatory cytokines. In addition, TH increased M2 macrophage polarization while inhibited M1 macrophage polarization. However, IRF4 knockout worsens neurological outcomes of stoke mice. The expression of pro-inflammatory cytokines were markedly increased in IRF4-/- mice as compared with IRF4+/+ mice at 8 h after stroke. Moreover, IRF4 knockout driven the macrophage polarization toward M1phenotype at 8 h after stroke. Most importantly, IRF4 knockout abolished the neuroprotective and anti-inflammatory effects of TH in IS.
Conclusion:
Together, we report for the first time that TH attenuates neuroinflammation following IS by modulating M1/M2 macrophage polarization through the upregulation of IRF4 expression.
