Ischemic preconditioning induces cortical microglial proliferation and a transcriptomic program of robust cell cycle...

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Ischemic preconditioning (IPC) protects the brain from severe ischemic injury.
• Understanding the molecular mechanisms of IPC is crucial for developing stroke therapies.
• Microglia play a key role in brain injury and repair.

Purpose of the Study:

• To investigate the role of microglia in ischemic preconditioning (IPC).
• To identify the signaling pathways involved in IPC-induced microglial responses.
• To explore the potential of targeting microglia for stroke treatment.

Main Methods:

• Transcriptomic analysis of isolated microglia after IPC.
• Ex vivo flow cytometry, immunofluorescent microscopy, and quantitative stereology.
• Assessment of microglial proliferation and activation markers (Iba1, Ki67, BrdU).
• Evaluation of IPC effects in CX3CR1-haploinsufficient and type I interferon signaling deficient mice.

Main Results:

• IPC induced significant upregulation of cell cycle and proliferation genes in cortical microglia.
• Microglia proliferation and activation were observed in the preconditioned hemisphere 72 hours post-IPC, without infarction.
• Microglial proliferation was dependent on fractalkine receptor (CX3CR1) signaling but not type I interferon signaling.

Conclusions:

• IPC stimulates a robust microglial proliferative response in the absence of infarction.
• Fractalkine signaling is a critical mediator of IPC-induced microglial proliferation.
• Targeting CX3CR1-dependent microglial pathways may offer a novel therapeutic strategy for stroke protection.