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Updated: Apr 19, 2026
Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
Perivascular microglia promote blood vessel disintegration in the ischemic penumbra
Valérie Jolivel1, Frank Bicker, Fabien Binamé
1Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Johannes Gutenberg University, University Medical Center, Mainz, Germany.
Abstract:
The contribution of microglia to ischemic cortical stroke is of particular therapeutic interest because of the impact on the survival of brain tissue in the ischemic penumbra, a region that is potentially salvable upon a brain infarct. Whether or not tissue in the penumbra survives critically depends on blood flow and vessel perfusion. To study the role of microglia in cortical stroke and blood vessel stability, CX3CR1(+/GFP) mice were subjected to transient middle cerebral artery occlusion and then microglia were investigated using time-lapse two-photon microscopy in vivo. Soon after reperfusion, microglia became activated in the stroke penumbra and started to expand cellular protrusions towards adjacent blood vessels. All microglia in the penumbra were found associated with blood vessels within 24 h post reperfusion and partially fully engulfed them. In the same time frame blood vessels became permissive for blood serum components. Migration assays in vitro showed that blood serum proteins leaking into the tissue provided molecular cues leading to the recruitment of microglia to blood vessels and to their activation. Subsequently, these perivascular microglia started to eat up endothelial cells by phagocytosis, which caused an activation of the local endothelium and contributed to the disintegration of blood vessels with an eventual break down of the blood brain barrier. Loss-of-microglia-function studies using CX3CR1(GFP/GFP) mice displayed a decrease in stroke size and a reduction in the extravasation of contrast agent into the brain penumbra as measured by MRI. Potentially, medication directed at inhibiting microglia activation within the first day after stroke could stabilize blood vessels in the penumbra, increase blood flow, and serve as a valuable treatment for patients suffering from ischemic stroke.
Insights
Microglia activation after ischemic stroke damages blood vessels in the brain penumbra. Inhibiting microglia may stabilize vessels, improve blood flow, and treat stroke.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- Microglia play a critical role in brain injury, particularly in the ischemic penumbra following stroke.
- The survival of brain tissue in the penumbra is dependent on blood flow and vessel perfusion.
- Understanding microglia's interaction with blood vessels is crucial for developing stroke therapies.
Purpose of the Study:
- To investigate the role of microglia in cortical stroke and their impact on blood vessel stability.
- To elucidate the mechanisms by which microglia affect the blood-brain barrier after ischemic injury.
Main Methods:
- Transient middle cerebral artery occlusion in CX3CR1(+/GFP) mice.
- In vivo time-lapse two-photon microscopy to observe microglia behavior.
- In vitro migration assays using blood serum proteins.
- Loss-of-function studies in CX3CR1(GFP/GFP) mice.
- Magnetic Resonance Imaging (MRI) to assess stroke volume and blood-brain barrier integrity.
Main Results:
- Activated microglia in the stroke penumbra extended protrusions towards and engulfed blood vessels within 24 hours post-reperfusion.
- Blood serum proteins acted as chemoattractants, recruiting and activating microglia towards blood vessels.
- Microglia phagocytosed endothelial cells, leading to blood vessel disintegration and blood-brain barrier breakdown.
- Loss of microglia function reduced stroke size and decreased contrast agent extravasation in the penumbra.
Conclusions:
- Microglia contribute to blood vessel instability and blood-brain barrier disruption after ischemic stroke.
- Inhibiting microglia activation early after stroke could potentially stabilize blood vessels and improve outcomes.
- Targeting microglia represents a promising therapeutic strategy for ischemic stroke treatment.
