A Visual Approach for Inducing Dolichoectasia in Mice to Model Large Vessel-Mediated Cerebrovascular Dysfunction

Dominic Simpson; Christopher D. Morrone; Darcy Wear; Jose Gutierrez; Wai Haung Yu

doi:10.3791/66792

Un approccio visivo per indurre la dolicoectasia nei topi per modellare la disfunzione cerebrovas...

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JoVE Journal Neuroscience

A Visual Approach for Inducing Dolichoectasia in Mice to Model Large Vessel-Mediated Cerebrovascular Dysfunction

Un approccio visivo per indurre la dolicoectasia nei topi per modellare la disfunzione cerebrovascolare mediata da grandi vasi

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04:29 min

May 17, 2024

DOI: 10.3791/66792-v

Dominic Simpson^1,2, Christopher D. Morrone¹, Darcy Wear^1,2, Jose Gutierrez³, Wai Haung Yu²

¹Brain Health Imaging Centre,Centre for Addiction and Mental Health, ²Department of Pharmacology and Toxicology,University of Toronto, ³Department of Neurology,Columbia University

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Overview

This study investigates cerebrovascular dysfunction using a transgenic mouse model to induce large blood vessel dilatation as a means to explore vascular dementia and Alzheimer's disease. The team demonstrates that a single elastase injection into the cisterna magna can sustain blood vessel dilation for up to three months, offering insights into vascular changes associated with mixed dementia.

Key Study Components

Area of Science

Neuroscience
Cerebrovascular Research
Alzheimer's Disease Studies

Background

Vascular changes are critical in the pathology of Alzheimer's disease.
Previous research demonstrated short-term dilation of blood vessels.
Little is understood about the overlap between vascular dementia and Alzheimer's.
This study aims to extend understanding of these conditions using an animal model.

Purpose of Study

To induce and analyze sustained blood vessel dilation in a mouse model.
To explore the implications of vascular changes for Alzheimer's disease pathology.
To test interventions that might mitigate vascular dysfunction in dementia.

Methods Used

Transgenic mouse model was utilized to examine stimulated blood vessel responses.
Injection of elastase into the cisterna magna was performed to induce vessel dilation.
The study included critical steps like surgical preparation and silicone compound injection for visualization.
Detailed surgical protocols were followed for precise manipulation and recovery monitoring of the mice.

Main Results

Dilatation of large blood vessels was observed, lasting up to three months.
Significant comparisons were made against control groups treated with PBS.
Illustrations showed vascular changes, including enlargement of the basilar artery and increased tortuosity.
Low mortality rates during procedures were noted, affirming the safety of methods used.

Conclusions

The study establishes a reliable model for inducing and studying vascular changes in relation to Alzheimer's disease.
The method enables further investigation of therapeutic strategies for vascular dementia.
Findings contribute to a better understanding of the relationship between cerebrovascular health and neurodegenerative conditions.

Frequently Asked Questions

What is the significance of using a transgenic mouse model?

Transgenic mouse models allow researchers to replicate human conditions more closely, making it easier to study the mechanisms behind diseases like Alzheimer's and vascular dementia.

How does the elastase injection impact cerebrovascular health?

The elastase injection induces dilation of blood vessels, which can help simulate the vascular changes observed in Alzheimer's disease, providing a controlled environment for study.

What types of outcomes were measured in this study?

Outcomes included the duration of vascular dilation, differences in morphology between treated and control groups, and implications for further drug testing.

What are the limitations of this study model?

While useful, the transgenic mouse model may not entirely replicate human neurological conditions, and results may vary based on genetic backgrounds and environmental factors.

Can this model be adapted for other types of interventions?

Yes, this model can be adapted for testing various compounds aimed at mitigating vascular dysfunction or exploring different neurological pathways relevant to dementia.

Dimostriamo l'induzione chimica della dilatazione dei grandi vasi sanguigni nei topi come modello per lo studio della disfunzione cerebrovascolare, che può essere utilizzato per la demenza vascolare e la modellazione del morbo di Alzheimer. Dimostriamo anche la visualizzazione del sistema vascolare iniettando un composto di gomma siliconica e fornendo una chiara guida visiva per misurare i cambiamenti nelle dimensioni dei vasi sanguigni.

Lo scopo della nostra ricerca è il modello di dolicoectasia in un modello murino transgenico per vedere il massimo impatto che i cambiamenti vascolari hanno sulla patologia della malattia di Alzheimer. Siamo in grado di dimostrare che una singola dose di iniezione di elastasi nella Cisterna magna dei topi è in grado di causare dilatazione fino a tre mesi. Non si sa molto sugli individui che soffrono sia di demenza vascolare che di Alzheimer.

Speriamo di colmare questa lacuna provocando cambiamenti vascolari in questi modelli murini transgenici per cercare di comprendere la patogenesi di questa forma di demenza mista. Studi precedenti sono stati in grado di dimostrare che la dilatazione dura fino a due settimane, nel nostro studio abbiamo dimostrato che la dilatazione dura fino a tre mesi con una bassa mortalità durante la nostra procedura chirurgica. La dilatazione riuscita dei grandi vasi sanguigni in un modello murino transgenico ci offre l'opportunità di testare farmaci per prevenire o migliorare i cambiamenti vascolari nella malattia di Alzheimer.

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