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Updated: Feb 28, 2026
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Dissection and Isolation of Murine Glia from Multiple Central Nervous System Regions
Published on: June 4, 2020
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Disentangling neuroimmune landscapes across peripheral activation paradigms resolves divergent glial state programs
Mahesh Chandra Kodali1,2,3,4, Zhengjun Wang3, Geng Lin3
1Department of Neurology, Harvard Medical School, Boston, MA, 02115, USA.
Research Square
|February 27, 2026
Summary
Distinct dosing of lipopolysaccharide (LPS) differentially impacts the brain. High-dose LPS causes neuroinflammation, while repeated low-dose LPS promotes protective microglial phagocytosis without inflammation.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Lipopolysaccharide (LPS) from gram-negative bacteria activates Toll-like receptor 4 (TLR4), modeling systemic inflammation and brain immune signaling.
- High-dose LPS induces acute neuroinflammation, while low-dose LPS may confer neuroprotection via innate immune memory.
Purpose of the Study:
- To compare the central nervous system (CNS) effects of repeated low-dose LPS with single high-dose LPS.
- To characterize the distinct neuroinflammatory and glial responses induced by different LPS dosing paradigms.
Main Methods:
- Utilized high-dose and repeated low-dose LPS models in mice.
- Performed whole-forebrain RNA sequencing (RNA-seq) and flow cytometry.
- Conducted cell-type-resolved transcriptional profiling.
Main Results:
- High-dose LPS triggered forebrain cytokine expression, disrupted glial homeostasis, and activated NF-κB and apoptosis pathways.
- Repeated low-dose LPS maintained glial homeostasis, increased microglial markers (IBA1/F4/80), and enriched phagocytosis pathways.
- Identified an expansion of CD45high CD11b+ myeloid cells with upregulated phagocytic markers (CD206) and suppressed inflammatory/apoptotic pathways under the low-dose regimen.
Conclusions:
- Distinct LPS dosing paradigms elicit differential glial responses in the CNS.
- Repeated low-dose LPS promotes phagocytic myeloid cell expansion and preserves glial homeostasis, contrasting with the neuroinflammatory effects of high-dose LPS.
- These findings clarify how LPS dosage influences neuroinflammation and glial function.
