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Updated: Aug 15, 2026
Triggering Reactive Gliosis In Vivo by a Forebrain Stab Injury
Published on: June 29, 2015
Reactive microgliosis engages distinct responses by microglial subpopulations after minor central nervous system
Martin Wirenfeldt1, Alicia Anne Babcock, Rune Ladeby
1Medical Biotechnology Center, University of Southern Denmark, Odense. mwnielsen@health.sdu.dk
Abstract:
Microglia are bone marrow-derived cells that constitute a facultative macrophage population when activated by trauma or pathology in the CNS. Endogenous CNS-resident microglia as well as exogenous (immigrant) bone marrow-derived cells contribute to reactive microgliosis, raising fundamental questions about the cellular composition, kinetics, and functional characteristics of the reactive microglial cell population. Bone marrow chimeric mice reconstituted with green fluorescent protein-expressing (GFP(+)) donor bone marrow cells were subjected to entorhinal cortex lesion, resulting in selective axonal degeneration and a localized microglial reaction in the hippocampus. Flow cytometric evaluation of individually dissected hippocampi differentiated immigrant GFP(+) microglia from resident GFP(-) microglia (CD11b(+)CD45(dim)) and identified a subset of mainly resident CD11b(+) microglia that was induced to express CD34. The proportion of immigrant GFP(+) microglia (CD11b(+)CD45(dim)) increased signficantly by 3 and 5 days postlesion and reached a maximum of 13% by 7 days. These cells expressed lower CD11b levels than resident microglia, forming a distinct subpopulation on CD11b/CD45 profiles. The proportion of CD34(+)CD11b(+) microglia was significantly increased at 3 days postlesion but had normalized by 5 and 7 days, when the microglial reaction is known to be at its maximum. Our results show that distinct subpopulations of microglia respond to minor CNS injury. The heterogeneity in microglial response may have functional consequences for repair and possibly therapy.
Insights
In CNS injury, both resident and immigrant microglia respond. Distinct microglial subpopulations show varied responses to central nervous system (CNS) damage, impacting repair and therapy.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells of the central nervous system (CNS).
- Reactive microgliosis, the microglial response to CNS injury, involves both resident and immigrant cells.
- The cellular dynamics and heterogeneity of reactive microglia remain incompletely understood.
Purpose of the Study:
- To investigate the cellular composition and kinetics of reactive microglia following CNS injury.
- To differentiate between resident and immigrant microglia and characterize their activation states.
- To explore the heterogeneity of microglial responses to axonal degeneration.
Main Methods:
- Utilized bone marrow chimeric mice reconstituted with green fluorescent protein (GFP)-expressing donor cells.
- Induced entorhinal cortex lesions to model CNS injury and axonal degeneration.
- Employed flow cytometry on dissected hippocampi to analyze microglial populations (CD11b, CD45, CD34 markers).
Main Results:
- Identified distinct subpopulations of resident (GFP-) and immigrant (GFP+) microglia.
- Immigrant microglia increased significantly post-lesion, reaching 13% by 7 days.
- A subset of resident microglia transiently expressed CD34, indicating a specific activation state.
Conclusions:
- CNS injury elicits heterogeneous microglial responses involving distinct resident and immigrant cell populations.
- The observed heterogeneity in microglial subpopulations may influence CNS repair mechanisms.
- Understanding microglial heterogeneity is crucial for developing effective CNS therapies.
