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Published on: July 25, 2011
Microglial PRMT2IP alleviates ischemia-induced brain injury
Min Zhang1, Jiexun Cai2, Wenting Su3
1Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, China; School of Medicine & Nursing, Huzhou University, Huzhou 313000, China; Laboratory for Clinical Medicine, Capital Medical University, Beijing 100069, China.
Microglial PRMT2IP (Protein arginine methyltransferase 2 interacting protein) is crucial for reducing brain injury after ischemic stroke. Upregulating PRMT2IP may offer a new therapeutic approach for stroke patients.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia are key drivers of neuroinflammation following ischemic stroke.
- PRMT2IP (C15orf39 in humans, 1700017B05Rik in mice) is implicated in microglial responses.
Purpose of the Study:
- To investigate the role of PRMT2IP in microglial activation and its impact on ischemic stroke outcomes.
- To explore the potential of PRMT2IP as a therapeutic target for stroke.
Main Methods:
- Mendelian randomization (MR) analysis to assess the causal link between PRMT2IP expression and stroke risk.
- Experimental models involving PRMT2IP overexpression and knockout in mice subjected to ischemic stroke.
- Investigation of the molecular mechanism involving PRMT2IP, PRMT2, and the NF-κB signaling pathway.
Main Results:
- MR analysis revealed a causal association between lower PRMT2IP expression and increased ischemic stroke risk.
- PRMT2IP expression was reduced in microglia from ischemic brain regions.
- Overexpression of PRMT2IP conferred protection against cerebral ischemia injury, whereas PRMT2IP knockout exacerbated stroke outcomes.
- PRMT2IP was found to interact with PRMT2, inhibiting the NF-κB signaling pathway via the PRMT2-IκBα axis and reducing inflammatory factors IL-6 and TNFα.
Conclusions:
- Microglial PRMT2IP acts as a critical negative regulator of the inflammatory response in ischemic stroke.
- PRMT2IP alleviates ischemia-induced brain injury by suppressing microglial activation and neuroinflammation.
- Enhancing PRMT2IP expression presents a promising therapeutic strategy to mitigate brain damage post-stroke.

