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Updated: Jul 14, 2026
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
Forebrain ischemia-reperfusion simulating cardiac arrest in mice induces edema and DNA fragmentation in the brain
Christina H Liu1, Shuning Huang, Young R Kim
1A.A. Martinos Center for Biomedical Imaging Charlestown, MA, USA.
Insights
Brain injury after cardiac arrest is common. This study shows a new MRI method using SPIONs to detect brain damage in live mice, offering hope for better diagnosis.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Cardiovascular Research
Background:
- Brain injury is a significant complication for cardiac arrest survivors.
- Current methods for detecting brain damage in live subjects post-cardiac arrest are limited.
- Transient bilateral carotid artery occlusion (BCAO) in mice models cardiac arrest and reperfusion.
Purpose of the Study:
- To investigate brain injury following simulated cardiac arrest and reperfusion in mice.
- To evaluate a novel in vivo MRI technique for detecting hippocampal and cortical damage.
- To assess the utility of SPION-cfos contrast agents for imaging brain injury.
Main Methods:
- Simulated cardiac arrest using 60-minute transient bilateral carotid artery occlusion (BCAO) in C57Black6 mice.
- In vivo T(2)*-weighted MRI with superparamagnetic iron oxide nanoparticles (SPIONs) linked to c-fos DNA (SPION-cfos).
- Measurement of SPION retention via T(2)* signal reduction and R(2)* elevation.
Main Results:
- Edema was observed after BCAO and reperfusion.
- Diffusion-weighted MRI showed hyperintensity in the striatum, thalamus, and cortex, but not the hippocampus.
- Significantly reduced SPION retention was found in the hippocampus and cortex of BCAO-treated mice compared to controls.
Conclusions:
- Brain injury following cardiac arrest can be detected in live animals using advanced MRI techniques.
- SPION-based MRI shows promise for non-invasively assessing neuronal damage in the brain.
- This approach may improve the diagnosis and management of brain injury after cardiac arrest.
Abstract:
Brain injury affects one-third of persons who survive after heart attack, even with restoration of spontaneous circulation by cardiopulmonary resuscitation. We studied brain injury resulting from transient bilateral carotid artery occlusion (BCAO) and reperfusion by simulating heart attack and restoration of circulation, respectively, in live C57Black6 mice. This model is known to induce neuronal death in the hippocampus, striatum, and cortex. We report the appearance of edema after transient BCAO of 60 minutes and 1 day of reperfusion. Hyperintensity in diffusion-weighted magnetic resonance imaging (MRI) was detectable in the striatum, thalamus, and cortex but not in the hippocampus. To determine whether damage to the hippocampus can be detected in live animals, we infused a T(2) susceptibility magnetic resonance contrast agent (superparamagnetic iron oxide nanoparticles [SPIONs]) that was linked to single-stranded deoxyribonucleic acid (DNA) complementary in sequence to c-fos messenger ribonucleic acid (SPION-cfos); we acquired in vivo T(2)*-weighted MRI 3 days later. SPION retention was measured as T(2)* (milliseconds) signal reduction or R(2)* value (s(-1)) elevation. We found that animals treated with 60-minute BCAO and 7-day reperfusion exhibited significantly less SPION retention in the hippocampus and cortex than sham-operated animals. These findings suggest that brain injury induced by cardiac arrest can be detected in live animals.
