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Author Spotlight: Assessing Ischemic Stroke Damage Through Middle Cerebral Artery Occlusion Model
Published on: August 11, 2023
Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke
Emilia Conti1,2,3, Noemi Carlini4,2, Benedetta Piccardi5,3
1Neuroscience Institute, National Research Council, 56124 Pisa, Italy conti@lens.unifi.it.
Abstract:
Stroke is one of the main causes of death and disability worldwide. Over the past decades, several animal models of focal cerebral ischemia have been developed allowing to investigate pathophysiological mechanisms underlying stroke progression. Despite intense preclinical research efforts, the need for noninvasive mouse models of vascular occlusion targeting the middle cerebral artery yet avoiding mechanical intervention is still pressing. Here, by applying the photothrombotic stroke model to the distal branch of the middle cerebral artery, we developed a novel strategy to induce a targeted occlusion of a large blood vessel in mice. This approach induces unilateral damage encompassing most of the dorsal cortex from the motor up to the visual regions 1 week after stroke. Pronounced limb dystonia one day after the damage is partially recovered after one week. Furthermore, we observe the insurgence of blood vessel leakage and edema formation in the peri-infarct area. Finally, this model elicits a notable inflammatory response revealed as a strong increase in astrocyte density and morphologic complexity in the perilesional region of the cortex compared with both other regions of the ipsilesional and contralesional hemispheres, and in sham-operated mice. To conclude, the stroke model we developed induces in mice the light-mediated occlusion of one of the main targets of human ischemic stroke, the middle cerebral artery, free from the limitations of commonly used preclinical models.
Insights
Researchers developed a novel, noninvasive photothrombotic stroke model in mice targeting the middle cerebral artery. This new method offers a valuable tool for studying stroke progression and potential therapies.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Animal Models of Disease
Background:
- Stroke is a leading cause of death and disability globally.
- Existing mouse models for focal cerebral ischemia often require mechanical intervention.
- There is a need for noninvasive models targeting the middle cerebral artery (MCA).
Purpose of the Study:
- To develop a novel, noninvasive photothrombotic stroke model in mice.
- To target the distal branch of the middle cerebral artery for occlusion.
- To investigate the pathophysiological mechanisms of stroke progression in a new model.
Main Methods:
- Application of the photothrombotic stroke model to the distal MCA.
- Induction of targeted vascular occlusion using light.
- Assessment of neurological deficits, including limb dystonia.
- Evaluation of blood-brain barrier integrity (leakage) and edema formation.
- Analysis of the inflammatory response, focusing on astrocyte density and morphology.
Main Results:
- The model successfully induced unilateral cortical damage in mice.
- Limb dystonia was observed one day post-stroke with partial recovery after one week.
- Significant blood vessel leakage and edema formation occurred in the peri-infarct area.
- A notable inflammatory response was evident, characterized by increased astrocyte density and complexity in the perilesional cortex.
Conclusions:
- A novel, light-mediated photothrombotic stroke model targeting the MCA was successfully developed in mice.
- This model avoids mechanical interventions, addressing limitations of current preclinical stroke models.
- The model allows for the study of stroke progression, including vascular leakage, edema, and inflammatory responses.

