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Updated: Sep 16, 2025
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Microglia interact with dendritic spines and regulate spine numbers after brain injury following resuscitation from a
Jacob M Basak1, Macy Falk1, Andra L Dingman2
1Department of Anesthesiology, University of Colorado Anschutz School of Medicine, Aurora, CO 80045, USA; Neuronal Injury and Plasticity Program, University of Colorado Anschutz School of Medicine, Aurora, CO 80045, USA.
Abstract:
Cognitive dysfunction is common after global cerebral ischemic injury caused by a cardiac arrest and is likely due in part to changes in synaptic function. Increasing evidence suggests microglial cells regulate synapse architecture and activity in various pathophysiologic conditions. However, the role of microglia in mediating synaptic injury after global cerebral ischemia has not been addressed. In this study, we use a mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR) to evaluate changes that occur in the numbers and morphology of both dendritic spines and microglia in the hippocampus after global cerebral ischemia. We also directly evaluate the interaction between dendritic spines and microglia after CA/CPR and assess how altering microglial numbers after the injury affects spine numbers. Our findings highlight that CA/CPR results in hippocampal spine loss that occurs in parallel with an increase in microglia numbers. Morphologic analysis of microglial cells demonstrates that CA/CPR leads to acute changes in cellular structure consistent with reactivity to the ischemic injury. We also show that microglia-spine contacts increase in the period following a CA/CPR injury along with co-localization between spines and phagocytic vesicles within microglia, suggesting a potential role for microglial engulfment in mediating spine loss. Finally, we demonstrate that pharmacologic depletion of microglia with PLX5622 after CA/CPR restores spine numbers in the injured brain. Collectively, these results emphasize the important role microglia exhibit in regulating synapse numbers in the setting of a CA/CPR injury and suggest targeting microglia-synapse interactions may improve cognitive outcomes following global ischemic brain injury.
Insights
Following cardiac arrest and resuscitation, microglia increase and contribute to synaptic loss in the hippocampus. Depleting microglia after injury restores synaptic density, suggesting a therapeutic target for cognitive dysfunction.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Cognitive dysfunction is a frequent outcome of global cerebral ischemic injury post-cardiac arrest.
- Microglial cells are increasingly recognized for their role in regulating synaptic structure and function.
- The specific involvement of microglia in synaptic injury following global cerebral ischemia remains unclear.
Purpose of the Study:
- To investigate the role of microglia in synaptic alterations after global cerebral ischemia.
- To examine microglial activation and their interaction with dendritic spines post-cardiac arrest and cardiopulmonary resuscitation (CA/CPR).
- To determine if modulating microglial populations impacts synaptic density after CA/CPR.
Main Methods:
- Utilized a mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR).
- Quantified dendritic spine and microglial numbers and morphology in the hippocampus.
- Assessed microglia-spine interactions and microglial phagocytosis.
- Employed pharmacologic depletion of microglia using PLX5622 post-CA/CPR.
Main Results:
- CA/CPR induced significant hippocampal spine loss concurrent with increased microglial numbers.
- Microglial cells exhibited morphological changes indicative of reactivity to ischemic injury.
- Increased microglia-spine contacts and co-localization with phagocytic vesicles suggested microglial engulfment of spines.
- Pharmacologic depletion of microglia post-CA/CPR led to the restoration of hippocampal spine density.
Conclusions:
- Microglia play a critical role in regulating synapse number following CA/CPR-induced global cerebral ischemia.
- Microglia-mediated synaptic changes, potentially through phagocytosis, contribute to cognitive deficits.
- Targeting microglia-synapse interactions presents a promising therapeutic strategy for improving cognitive outcomes after ischemic brain injury.
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