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Updated: Jul 18, 2026
Live Imaging and Characterization of Microglia Dynamics and Interactions with Synapses in Diseased Murine Retina
Published on: January 16, 2026
Evidence for synaptic stripping by cortical microglia
Bruce D Trapp1, Jerome R Wujek, Gerson A Criste
1Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA. trappb@ccf.org
Abstract:
Recent studies have described significant demyelination and microglial activation in the cerebral cortex of brains from multiple sclerosis patients. To date, however, experimental models of cortical demyelination or cortical inflammation have not been extensively studied. In this report we describe focal cortical inflammation induced by stereotaxic injection of killed bacteria (BCG), followed 1 month later by subcutaneous injection of the same antigen, a protocol that overcomes the immune privilege of the cortex. Intracerebral BCG injection produced focal microglial activation at the injection site (termed acute lesion). Ten days after peripheral challenge (termed immune-mediated lesion), larger areas and higher densities of activated microglia were found near the injection site. In both paradigms, activated microglia and/or their processes closely apposed neuronal perikarya and apical dendrites. In the immune-mediated lesions, approximately 45% of the axosomatic synapses was displaced by activated microglia. Upon activation, therefore, cortical microglial migrate to and strip synapses from neuronal perikarya. Since neuronal pathology was not a feature of either the acute or immune-mediated lesion, synaptic stripping by activated microglia may have neuroprotective consequences.
Insights
Researchers developed a new model for studying cortical inflammation and demyelination. Activated microglia in the brain cortex were observed to strip synapses, potentially offering neuroprotection in multiple sclerosis models.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) involves demyelination and microglial activation in the cerebral cortex.
- Existing experimental models for cortical demyelination or inflammation are limited.
- The brain cortex's immune privilege poses challenges for studying inflammatory processes.
Purpose of the Study:
- To establish and characterize a novel experimental model of focal cortical inflammation.
- To investigate the behavior and consequences of microglial activation in the cerebral cortex.
- To explore the potential neuroprotective role of microglial synaptic stripping.
Main Methods:
- Stereotaxic injection of killed bacteria (BCG) into the rodent cerebral cortex to induce acute lesions.
- Subcutaneous injection of BCG 1 month later to elicit immune-mediated lesions, overcoming cortical immune privilege.
- Histological analysis to assess microglial activation, density, and proximity to neurons.
- Quantification of synaptic stripping by activated microglia using electron microscopy.
Main Results:
- Intracerebral BCG injection induced focal microglial activation (acute lesions).
- Peripheral BCG challenge led to larger areas and higher densities of activated microglia (immune-mediated lesions).
- Activated microglia closely associated with neuronal structures and displaced approximately 45% of axosomatic synapses in immune-mediated lesions.
- No significant neuronal pathology was observed in either lesion type.
Conclusions:
- Activated cortical microglia migrate to and strip synapses from neuronal perikarya.
- Synaptic stripping by microglia in this model may serve a neuroprotective function.
- This model provides a valuable tool for studying cortical inflammation and its impact on neuronal-microglial interactions in CNS diseases like MS.
