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09:12
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
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Long-Term Microgliosis Driven by Acute Systemic Inflammation.
Alissa Trzeciak1, Yelena V Lerman1, Tae-Hyoun Kim1
1Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642.
Journal of Immunology (Baltimore, Md. : 1950)
|October 18, 2019
Summary
Severe sepsis causes brain immune cell changes. Early monocyte infiltration leads to lasting microglial activation, potentially impacting future brain health and disease.
Area of Science:
- Immunology
- Neuroscience
- Pathology
Background:
- Severe sepsis is a major cause of intensive care unit morbidity, characterized by systemic inflammation and organ injury.
- While sepsis affects multiple organs, its impact on brain immunity and the development of chronic brain dysfunction is poorly understood.
- Understanding sepsis-induced brain changes is crucial for managing long-term neurological consequences.
Purpose of the Study:
- To investigate the immunological consequences of severe sepsis in the brain.
- To determine the long-term effects of sepsis on brain-resident immune cells, specifically microglia.
- To explore the role of monocyte infiltration in sepsis-induced neuroinflammation.
Main Methods:
- Utilized C57BL/6 sepsis mouse models to induce varying degrees of sepsis severity and observe recovery.
- Monitored monocyte infiltration and proinflammatory cytokine levels in the brain during early sepsis.
- Quantified brain-resident microglia populations and assessed their activation state in recovered septic mice.
- Investigated the proliferation of microglia and the role of CCR2 in knockout mouse models.
Main Results:
- Sepsis induced significant monocyte infiltration into the brain with elevated proinflammatory cytokines in early stages.
- In recovered mice, while monocyte levels normalized, there was a significant increase in activated microglia in the cortex.
- Microglial proliferation was identified as the primary driver for the increased microglia numbers, a process dependent on CCR2.
- Early monocyte infiltration during sepsis leads to persistent alterations in microglia.
Conclusions:
- Sepsis causes lasting changes to brain microglia, driven by early monocyte infiltration and subsequent proliferation.
- These persistent microglial alterations may influence the brain's response to subsequent infections and neuropathological conditions.
- The findings highlight a potential mechanism for sepsis-associated chronic brain dysfunction.
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