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Updated: May 8, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Early morphofunctional plasticity of microglia in response to acute lipopolysaccharide
C Madore1, C Joffre, J C Delpech
1INRA, Nutrition and Integrative Neurobiology, UMR 1286, F-33000 Bordeaux, France; Univ. Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, F-33000 Bordeaux, France.
Abstract:
Within the central nervous system (CNS) the traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression. This led to the concept of "resting" versus "activated" microglia. However, this is misleading because multiple phenotypic and morphological stages of microglia can influence neuronal structure and function in any condition and recent evidence extends their role to healthy brain homeostasis. The present work was thus aimed at reappraising the concept of morphofunctional activity of microglia in a context of peripheral acute immune challenge, where microglial activity is known to be modified, using the new state-of-the-art techniques available. To do so, mice were injected peripherally with lipopolysaccharide, a potent inducer of cerebral inflammation, and we assessed early cytokines production, phenotype, motility and morphology of microglial cells. Our results showed that LPS induced a widespread inflammatory response both peripherally and centrally, as revealed by the quantification of cytokines levels. We also found an alteration of microglial motility that was confirmed by in vivo studies showing an overall reduction of microglial processes length in the hippocampus of LPS-treated animals. Finally, analysis of various surface receptors expression revealed that LPS did not significantly impact microglial phenotype 2h after the injection but rather induced an increase of CD11b(+)/CD45(high) cells. These latter may be at the vasculature, at the CNS vicinity, or may have invaded the CNS.
Insights
Acute peripheral inflammation alters microglia in the brain, impacting their movement and morphology. This study reveals changes in microglial cells following lipopolysaccharide challenge, affecting brain homeostasis.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the central nervous system's immune cells, traditionally viewed as "resting" or "activated," have diverse roles in brain homeostasis and disease.
- Recent evidence highlights microglia's dynamic functions beyond infection, influencing neuronal structure and function in healthy brains.
Purpose of the Study:
- To re-evaluate microglial morphofunctional activity during acute peripheral immune challenges.
- To investigate the impact of peripheral lipopolysaccharide (LPS) administration on microglial cells within the central nervous system (CNS).
Main Methods:
- Mice were injected peripherally with lipopolysaccharide (LPS).
- Assessed early cytokine production, microglial phenotype, motility, and morphology using advanced techniques.
- In vivo studies quantified microglial process length in the hippocampus.
Main Results:
- LPS induced a widespread inflammatory response, evidenced by increased peripheral and central cytokine levels.
- Microglial motility was altered, with reduced microglial processes length observed in the hippocampus of LPS-treated mice.
- While microglial phenotype remained largely unchanged at 2 hours post-injection, an increase in CD11b(+)/CD45(high) cells was noted.
Conclusions:
- Peripheral immune challenges significantly modify microglial cell behavior and morphology within the CNS.
- The study challenges the simplistic "resting" vs. "activated" dichotomy, emphasizing microglia's complex roles in neuroinflammation.
- Increased CD11b(+)/CD45(high) cells suggest potential roles in immune surveillance at the CNS borders or infiltration.
