Related Experiment Video
Updated: Jun 18, 2025
Author Spotlight: Establishing a Reliable Distal MCA Occlusion Model in Mice for Stroke Research
Published on: December 15, 2023
Hippocampal infarction and generalized seizures predict early mortality after endovascular middle cerebral artery
Xuyan Jin1, Takahiko Imai1, Andreia Morais1
1Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, USA.
Abstract:
Endovascular middle cerebral artery occlusion (MCAO) is a widely used experimental ischemic stroke model. However, the model carries high early mortality. Our aim was to investigate the factors that influence early mortality within 48 h of reperfusion after transient MCAO. Using C57BL/6 mice, we induced 1-hour endovascular filament MCAO. To introduce heterogeneity of infarct volumes, a subset of animals had additional tandem common carotid artery occlusion (MCAO+CCAO). Continuous video monitoring was used to gain insight into the cause of death. Mortality within 48 h was 25% in the pooled cohort. All animals with early mortality suffered from infarcts in the hippocampus, sometimes accompanied by infarcts in the thalamus and midbrain, which occurred exclusively in the MCAO+CCAO group. All animals with early mortality developed convulsive seizures captured on video monitoring. None of the animals that did not develop convulsive seizures died. Among the three regions, hippocampal infarction appeared necessary for convulsive seizures and early mortality. Our data highlight seizures as the primary cause of mortality within the first 48 h after endovascular filament MCAO, linked to hippocampal infarction. Since hippocampal blood supply is mainly from the posterior cerebral artery (PCA), avoiding concurrent PCA ischemia can decrease mortality in proximal MCAO models.
Insights
Seizures following middle cerebral artery occlusion (MCAO) in mice are linked to hippocampal damage and cause early mortality. Avoiding posterior cerebral artery ischemia may reduce deaths in MCAO stroke models.
Area of Science:
- Neuroscience
- Stroke Research
- Animal Models
Background:
- Endovascular middle cerebral artery occlusion (MCAO) is a common experimental stroke model.
- This model is associated with high early mortality rates.
- Understanding factors influencing early mortality is crucial for improving experimental stroke research.
Purpose of the Study:
- To investigate factors contributing to early mortality within 48 hours after transient MCAO in mice.
- To identify the primary cause of death in this experimental stroke model.
- To provide insights for reducing mortality in MCAO models.
Main Methods:
- Induction of 1-hour endovascular filament MCAO in C57BL/6 mice.
- Inclusion of a subset with tandem common carotid artery occlusion (MCAO+CCAO) to create varied infarct sizes.
- Continuous video monitoring to record animal behavior and cause of death.
Main Results:
- Overall 48-hour mortality rate was 25%.
- Early mortality was associated with hippocampal, thalamic, and midbrain infarcts, particularly in the MCAO+CCAO group.
- All deceased animals exhibited convulsive seizures; none of the survivors did.
- Hippocampal infarction was identified as a necessary factor for seizures and mortality.
Conclusions:
- Convulsive seizures are the primary cause of early mortality (within 48 hours) after endovascular filament MCAO.
- Hippocampal infarction is directly linked to these seizures and subsequent mortality.
- Minimizing concurrent posterior cerebral artery ischemia may decrease mortality in MCAO stroke models.
