Related Experiment Video
Updated: Jun 8, 2026
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Severity of Peripheral Infection Differentially Affects Brain Functions in Mice via Microglia-Dependent and
Yen-Phung Le1,2, Kozo Saito1,2, Bijay Parajuli1,2
1Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, Japan.
Abstract:
Peripheral infection induces inflammation in peripheral tissues and the brain, impacting brain function. Glial cells are key players in this process. However, the effects of peripheral infection on glial activation and brain function remain unknown. Here, we showed that varying degrees of peripheral infection had different effects on the regulation of brain functions by microglia-dependent and -independent mechanisms. Acute mild infection (one-day LPS challenge: 1LPS) exacerbated middle cerebral artery occlusion (MCAO) injury, and severe infection (four-day LPS challenge: 4LPS) for one week suppressed it. MCAO injury was assessed by triphenyltetrazolium chloride staining. We observed early activation of microglia in the 1LPS and 4LPS groups. Depleting microglia with a colony-stimulating factor-1 receptor (CSF1R) antagonist had no effect on 1LPS-induced brain injury exacerbation but abolished 4LPS-induced protection, indicating microglial independence and dependence, respectively. Microglia-independent exacerbation caused by 1LPS involved peripheral immune cells including macrophages. RNA sequencing analysis of 4LPS-treated microglia revealed increased factors related to anti-inflammatory and neuronal tissue repair, suggesting their association with the protective effect. In conclusion, varying degrees of peripheral inflammation had contradictory effects (exacerbation vs. protection) on MCAO, which may be attributed to microglial dependence. Our findings highlight the significant impact of peripheral infection on brain function, particularly in relation to glial cells.
Insights
Peripheral infection impacts brain function differently based on severity. Mild infection worsens stroke injury, while severe infection protects it, involving distinct glial cell mechanisms.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Peripheral infection and inflammation affect brain function.
- Glial cells, particularly microglia, are implicated in neuroinflammation.
- The precise role of peripheral infection severity on glial activation and brain injury is unclear.
Purpose of the Study:
- To investigate the differential effects of varying peripheral infection severities on brain function and injury.
- To elucidate the roles of microglia-dependent and -independent mechanisms in these effects.
Main Methods:
- Induction of peripheral infection using lipopolysaccharide (LPS) challenges of varying durations (1-day and 4-day).
- Middle cerebral artery occlusion (MCAO) model to assess brain injury.
- Microglia depletion using a colony-stimulating factor-1 receptor (CSF1R) antagonist.
- Analysis of peripheral immune cells and RNA sequencing of microglia.
Main Results:
- Acute mild infection (1-day LPS) exacerbated MCAO injury via microglia-independent mechanisms involving peripheral immune cells.
- Severe infection (4-day LPS) protected against MCAO injury through microglia-dependent mechanisms.
- Microglia activation was observed in both infection groups.
- RNA sequencing revealed anti-inflammatory and neuroprotective factors in microglia from the 4-day LPS group.
Conclusions:
- Peripheral infection severity dictates its impact on brain injury, causing exacerbation or protection.
- Microglial involvement is crucial for the protective effects of severe peripheral infection but not for the exacerbation by mild infection.
- Findings underscore the complex interplay between peripheral inflammation, glial cells, and brain injury outcomes.
Related Concept Videos
01:26Bacterial Meningitis II: Pathophysiology
01:26Encephalitis ll: Pathophysiology