Related Experiment Video
Updated: Jul 17, 2026
The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse
Published on: July 25, 2011
TREM2-IGF1 Mediated Glucometabolic Enhancement Underlies Microglial Neuroprotective Properties During Ischemic Stroke
Sheng Yang1,2, Chuan Qin1,2, Man Chen1,2
1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Abstract:
Microglia, the major resident immune cells in the central nervous system, serve as the frontline soldiers against cerebral ischemic injuries, possibly along with metabolic alterations. However, signaling pathways involved in the regulation of microglial immunometabolism in ischemic stroke remain to be further elucidated. In this study, using single-nuclei RNA sequencing, a microglial subcluster up-regulated in ischemic brain tissues is identified, with high expression of Igf1 and Trem2, neuroprotective transcriptional signature and enhanced oxidative phosphorylation. Microglial depletion by PLX3397 exacerbates ischemic brain damage, which is reversed by repopulating the microglia with high Igf1 and Trem2 phenotype. Mechanistically, Igf1 serves as one of the major down-stream molecules of Trem2, and Trem2-Igf1 signaling axis regulates microglial functional and metabolic profiles, exerting neuroprotective effects on ischemic stroke. Overexpression of Igf1 and supplementation of cyclocreatine restore microglial glucometabolic levels and cellular functions even in the absence of Trem2. These findings suggest that Trem2-Igf1 signaling axis reprograms microglial immunometabolic profiles and shifts microglia toward a neuroprotective phenotype, which has promising therapeutic potential in treating ischemic stroke.
Insights
Microglia play a key role in ischemic stroke by reprogramming their metabolism. The Trem2-Igf1 signaling pathway enhances microglial neuroprotection, offering potential therapeutic strategies for stroke.
Area of Science:
- Neuroscience
- Immunology
- Metabolism
Background:
- Microglia are crucial immune cells in the central nervous system, responding to cerebral ischemic injuries.
- Understanding microglial immunometabolism in ischemic stroke is essential for developing effective treatments.
Purpose of the Study:
- To elucidate the signaling pathways regulating microglial immunometabolism in ischemic stroke.
- To identify specific microglial phenotypes and their roles in neuroprotection.
Main Methods:
- Single-nuclei RNA sequencing was employed to identify microglial subclusters in ischemic brain tissues.
- Microglial depletion and repopulation experiments using PLX3397 were conducted.
- Mechanistic studies investigated the role of Trem2-Igf1 signaling and the effects of Igf1 overexpression and cyclocreatine supplementation.
Main Results:
- A specific microglial subcluster with high Igf1 and Trem2 expression, neuroprotective signature, and enhanced oxidative phosphorylation was identified in ischemic brains.
- Microglial depletion worsened ischemic brain damage, while repopulation with the identified phenotype reversed this effect.
- The Trem2-Igf1 signaling axis was found to regulate microglial function and metabolism, conferring neuroprotection. Igf1 and cyclocreatine restored function independently of Trem2.
Conclusions:
- The Trem2-Igf1 signaling axis reprograms microglial immunometabolism towards a neuroprotective phenotype in ischemic stroke.
- Targeting this pathway presents a promising therapeutic strategy for treating ischemic stroke.
More Related Videos
Related Concept Videos
01:15Ischemic Stroke l: Introduction
01:15Ischemic Stroke ll: Pathophysiology