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Updated: Jun 24, 2026

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Cortical microinfarcts potentiate recurrent ischemic injury through NLRP3-dependent trained immunity
Yiwei Feng1,2,3, Lishan Lin1,2, Tengteng Wu1,2,4
1Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Abstract:
Microinfarcts are common among the elderly and patients with microinfarcts are more vulnerable to another stroke. However, the impact of microinfarcts on recurrent stroke has yet to be fully understood. The purpose of this study was to explore the negative effects of microinfarcts on recurrent stroke. To achieve this, two-photon laser was used to induce microinfarcts, while photothrombotic stroke was induced on the opposite side. The results showed that microinfarcts led to trained immunity in microglia, which worsened the pro-inflammatory response and ischemic injury in the secondary photothrombotic stroke. Additionally, the study clarified the role of NLRP3 in microglial nuclei, indicating that it interacts with the MLL1 complex through NACHT domain and increases H3K4 methylation, which suggests that NLRP3 is critical in the formation of innate immune memory caused by microinfarcts. Furthermore, the knockout of NLRP3 in microglia alleviated the trained immunity and reduced the harmful effects of microinfarcts on recurrent stroke. This study emphasizes the detrimental effect of trained immunity on recurrent stroke and highlights the critical role of NLRP3 in mediating the formation of this memory, which may offer a potential therapeutic target for mitigating recurrent strokes.
Insights
Microinfarcts worsen recurrent stroke by causing trained immunity in microglia. Targeting NLRP3 in microglia may prevent this harmful immune memory and reduce stroke recurrence.
Area of Science:
- Neuroscience
- Immunology
- Stroke Research
Background:
- Microinfarcts are prevalent in the elderly and increase stroke vulnerability.
- The precise impact of microinfarcts on recurrent stroke remains unclear.
Purpose of the Study:
- To investigate the detrimental effects of microinfarcts on recurrent stroke.
- To elucidate the underlying mechanisms of microinfarct-induced exacerbation of stroke.
Main Methods:
- Induction of microinfarcts using two-photon laser and secondary photothrombotic stroke.
- Analysis of microglial activation, inflammatory responses, and molecular pathways.
- Utilizing NLRP3 knockout in microglia for mechanistic studies.
Main Results:
- Microinfarcts induced trained immunity in microglia, enhancing pro-inflammatory responses and ischemic injury in secondary strokes.
- NLRP3 in microglia was identified to interact with the MLL1 complex, increasing H3K4 methylation and mediating innate immune memory.
- NLRP3 knockout in microglia attenuated trained immunity and mitigated the adverse effects of microinfarcts on recurrent stroke.
Conclusions:
- Trained immunity plays a significant role in the detrimental effects of microinfarcts on recurrent stroke.
- NLRP3 is crucial for the formation of microinfarct-induced innate immune memory.
- Targeting NLRP3 in microglia presents a potential therapeutic strategy for recurrent stroke prevention.
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