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Updated: Aug 11, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Targeting microglial PPARα ameliorates the outcome of ischemic stroke by enhancing interaction with infiltrating
Tong Ren1, Maoshu Zhu2, Xilin Jiang1
1Xiamen Cardiovascular Hospital of Xiamen University, Fujian Branch of National Clinical Research Center for Cardiovascular Diseases, School of Medicine, Xiamen University, Xiamen 361002, P.R. China.
Abstract:
The interaction between infiltrating immune cells and brain-resident cells is critical for inducing an inflammatory response to ischemic stroke. However, the direct effects of CD11b+CD45int microglia in the brain on infiltrating CD11b+CD45highLy6G- monocytes/macrophages (Mos/MΦs) and the precise molecular mechanisms underlying these effects after acute ischemic stroke (AIS) remain unknown. Here, ischemia-induced microglial peroxisome proliferator-activated receptor-alpha (PPARα) downregulation was found to be critical for enhancing the inflammatory response and exacerbating ischemic brain injury by priming peripheral pro-inflammatory Mo/MΦ infiltration. The targeted microglial PPARα signal exerted neuroprotective effects on ischemic stroke by protecting blood-brain barrier (BBB) integrity and inhibiting the infiltration of innate immune cells. Furthermore, overexpression of microglia-specific PPARα exerted neuroprotective effects by enhancing the interleukin (IL)-4 signal-mediated crosstalk of microglia-MΦs. Therefore, our study reveals that ischemia-induced microglial PPARα deficiency expands the inflammatory response and exacerbates ischemic brain injury by enhancing the interaction with infiltrating peripheral Mos/MΦs and suggests that targeting microglial PPARα is a potential therapeutic strategy for improving acute cerebral ischemic injury.
Insights
Microglial peroxisome proliferator-activated receptor-alpha (PPARα) downregulation exacerbates ischemic stroke by promoting inflammatory cell infiltration. Targeting microglial PPARα offers a potential therapeutic strategy for acute cerebral ischemic injury.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Immune cell interactions with brain cells drive inflammation in ischemic stroke.
- The specific role of microglia in modulating infiltrating monocytes/macrophages after stroke is unclear.
Purpose of the Study:
- Investigate the role of microglial peroxisome proliferator-activated receptor-alpha (PPARα) in acute ischemic stroke (AIS).
- Elucidate the molecular mechanisms by which microglia influence peripheral immune cell infiltration and brain injury.
Main Methods:
- Studied ischemia-induced changes in microglial PPARα expression in an AIS model.
- Investigated the impact of microglial PPARα modulation on immune cell infiltration and blood-brain barrier (BBB) integrity.
- Examined the effects of microglia-specific PPARα overexpression on neuroprotection and immune cell crosstalk.
Main Results:
- Ischemia downregulated microglial PPARα, enhancing inflammation and exacerbating brain injury.
- Targeting microglial PPARα protected the BBB and reduced innate immune cell infiltration.
- Overexpressing microglial PPARα promoted neuroprotection via IL-4 signaling-mediated microglia-macrophage crosstalk.
Conclusions:
- Ischemia-induced microglial PPARα deficiency worsens stroke outcomes by increasing peripheral immune cell interaction.
- Microglial PPARα is a potential therapeutic target for acute ischemic stroke.
