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Modeling Stroke in Mice: Permanent Coagulation of the Distal Middle Cerebral Artery
Published on: July 31, 2014
Hypothalamic, thalamic and hippocampal lesions in the mouse MCAO model: Potential involvement of deep cerebral
Mohamad El Amki1, Thomas Clavier2, Nicolas Perzo1
1Institut National de la Santé et de la Recherche Médicale (Inserm), U982, Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan, France.
Abstract:
Intraluminal monofilament occlusion of the middle cerebral artery (MCAO) in mice is the most used rodent model to study the pathophysiology of stroke. However, this model often shows brain damage in regions not supplied by the MCA such as the hypothalamus, hippocampus and thalamus. Several studies have suggested some explanations on these localized infarcts. We aim to provide an alternative explanation which could allow each experimenter to better grasp the MCAO model. We propose that the MCA occlusion by the monofilament also occludes deep and small cerebral arteries arising directly from the internal carotid artery, proximally to the origin of MCA. Then, drawbacks and pitfalls of the MCAO model must be appreciated and the almost systematic risk of inducing lesions in some unwanted territories for neuroanatomical reasons, i.e. vascular connections between deep arteries and hypothalamic, thalamic and hippocampal areas in rodents has to be integrated.
Insights
The middle cerebral artery occlusion (MCAO) model in rodents can cause unintended brain damage. This occurs because the filament may also block deep arteries, leading to infarcts in areas not typically supplied by the MCA.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Stroke Models
Background:
- The intraluminal monofilament occlusion of the middle cerebral artery (MCAO) is a widely used rodent model for studying stroke pathophysiology.
- This model frequently results in brain damage in areas not directly supplied by the MCA, including the hypothalamus, hippocampus, and thalamus.
- Existing explanations for these off-target infarcts are insufficient for researchers to fully understand the MCAO model.
Purpose of the Study:
- To propose an alternative explanation for localized infarcts observed in the MCAO rodent model.
- To enhance experimentalists' understanding of the MCAO model's inherent limitations.
- To highlight the importance of considering neuroanatomical vascular connections in interpreting MCAO study results.
Main Methods:
- Review of existing literature on MCAO rodent models and stroke pathophysiology.
- Analysis of potential vascular occlusions caused by the intraluminal monofilament.
- Consideration of rodent cerebrovascular anatomy, particularly the origins of deep cerebral arteries.
Main Results:
- The monofilament used in MCAO may inadvertently occlude deep and small cerebral arteries originating directly from the internal carotid artery, proximal to the MCA origin.
- This proximal occlusion can lead to infarcts in brain regions not solely dependent on the MCA.
- The study identifies specific vascular connections between these deep arteries and hypothalamic, thalamic, and hippocampal areas in rodents.
Conclusions:
- The MCAO model carries an inherent risk of inducing lesions in unintended brain territories due to the monofilament's placement.
- Neuroanatomical vascular connections explain the frequent occurrence of infarcts in the hypothalamus, hippocampus, and thalamus.
- Researchers must appreciate these drawbacks and integrate the risk of off-target lesions into their MCAO experimental designs and interpretations.
