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Published on: July 31, 2017
A likely protective effect of dimethyl itaconate on cerebral ischemia/reperfusion injury
Di Zhang1, Zhengfang Lu1, Zhen Zhang1
1Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Abstract:
As a membrane-permeable derivative of itaconate, dimethyl itaconate (DMI) was recently showed to limit inflammatory response of activated macrophages, and to decrease the generation of reactive oxygen species and reduce cardiac ischemia/reperfusion injury. However, the effect of DMI in the context of cerebral ischemia/reperfusion injury remains unclear. Here, we treated the transient middle cerebral artery occlusion (tMCAO) mice with DMI or saline at the beginning of occlusion, and allowed them to recover for 3 days. We found that DMI obviously decreased the neurologic deficit score. Further, DMI significantly inhibited the toxic conversion of the peri-infarct microglia, and decreased the protein level of interleukin 1β. The present findings suggest that DMI might be recognized as a promising candidate for the treatment of ischemic stroke.
Insights
Dimethyl itaconate (DMI) shows promise for treating ischemic stroke by reducing neurological deficits and inhibiting harmful inflammation in the brain following a stroke. This derivative of itaconate offers a potential new therapeutic avenue.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Dimethyl itaconate (DMI), a derivative of itaconate, is known to reduce inflammation and oxidative stress.
- Previous studies show DMI mitigates cardiac ischemia/reperfusion injury.
- The therapeutic potential of DMI in cerebral ischemia/reperfusion injury is currently unknown.
Purpose of the Study:
- To investigate the efficacy of dimethyl itaconate (DMI) in a mouse model of ischemic stroke.
- To determine if DMI can reduce neurological deficits and brain inflammation after cerebral ischemia/reperfusion injury.
Main Methods:
- Transient middle cerebral artery occlusion (tMCAO) model was used in mice.
- Mice were treated with DMI or saline at the onset of occlusion.
- Neurological deficit scores were assessed after 3 days of recovery.
Main Results:
- DMI treatment significantly decreased neurological deficit scores in tMCAO mice.
- DMI inhibited the detrimental transformation of peri-infarct microglia.
- DMI reduced the protein levels of pro-inflammatory interleukin 1β.
Conclusions:
- Dimethyl itaconate (DMI) demonstrates a neuroprotective effect against cerebral ischemia/reperfusion injury.
- DMI may serve as a potential therapeutic agent for ischemic stroke treatment.
- Inhibition of microglial activation and reduction of IL-1β are key mechanisms of DMI's action.
