Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult

Stephanie A. Herrlinger; Qiang Shao; Li Ma; Melinda Brindley; Jian-Fu Chen

doi:10.3791/56486

Tworzenie mysich modeli zaburzeń neurologicznych wywołanych wirusem Zika przy użyciu strategii in...

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JoVE Journal Neuroscience

Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult

Tworzenie mysich modeli zaburzeń neurologicznych wywołanych wirusem Zika przy użyciu strategii iniekcji domózgowych: embrionalnej, noworodkowej i dorosłej

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09:39 min

April 26, 2018

DOI: 10.3791/56486-v

Stephanie A. Herrlinger¹, Qiang Shao², Li Ma², Melinda Brindley³, Jian-Fu Chen²

¹Biomedical and Health Sciences Institute,University of Georgia, ²Center for Craniofacial Molecular Biology,University of Southern California, ³Department of Infectious Diseases, College of Veterinary Medicine,University of Georgia

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Overview

This study presents a method for creating in vivo models of Zika virus infection in the brain using a mouse model. The primary focus is on understanding the pathology and mechanisms of Zika virus-induced microcephaly at various developmental stages, which has implications for therapies and diagnostics.

Key Study Components

Area of Science

Neuroscience
Virology
In vivo models

Background

Zika virus infection is linked to microcephaly in fetuses.
Understanding viral mechanics in the brain is crucial for addressing neurodevelopmental disorders.
This technique can also extend to other flavivirus infections, like dengue.

Purpose of Study

To establish a reliable method for studying Zika virus infections in the brain.
To investigate the effects of the virus at embryonic, neonatal, and adult stages.
To explore implications for therapy and diagnosis of associated disorders.

Methods Used

A surgical method for intracerebral inoculation of Zika virus in mouse models.
The primary biological model involves injecting embryos, neonatal pups, and adult mice.
Important steps include preparing injection syringes, anesthetizing subjects, and injecting Zika virus into specified brain regions.
Monitoring recovery and ensuring sterile conditions during surgical procedures are emphasized.

Main Results

The technique allows for controlled infection of the brain, facilitating detailed study of viral pathogenesis.
Significant insights into the development of neurodevelopmental issues related to Zika infection are anticipated.
Potentially applicable to other flavivirus models enhances the method's versatility.

Conclusions

This study establishes a foundational protocol for investigating Zika virus impact on brain development.
Insights gained may enable advancements in understanding and treating Zika-related disorders.

Frequently Asked Questions

What are the advantages of this model for studying Zika virus?

The model allows precise control of viral inoculation in various developmental stages and can yield insights into the pathology of Zika virus infections.

How is the biological model implemented?

The model involves injecting Zika virus into the brains of embryos, neonatal pups, or adult mice to study the disease's progression and effects.

What types of data are obtained from this method?

Data obtained may include viral load, developmental outcomes, and neurodevelopmental changes associated with Zika infection.

What are the limitations of this method?

Considerations include the invasive nature of the procedure and ensuring anesthetic adequacy during surgery to minimize risks to the animals.

How can this technique be adapted for other infections?

By modifying virus strains used or adjusting injection protocols, this method can be adapted to study other flavivirus infections, such as dengue.

What is the significance of studying Zika virus in the brain?

Understanding the viral mechanisms in the brain is crucial for developing interventions to address microcephaly and other neurodevelopmental issues associated with infection.

Tutaj opisujemy metodę tworzenia modelu mikrocefalii wywołanej wirusem Zika u myszy. Protokół ten obejmuje metody inokulacji śródmózgowej wirusa Zika w stadium embrionalnym, noworodkowym i dorosłym.

Ogólnym celem przedstawionych metod chirurgicznych jest stworzenie modeli in vivo wewnątrzczaszkowego zakażenia wirusem Zika. Metoda ta może pomóc w odpowiedzi na kluczowe pytanie w tej dziedzinie, takie jak patologia i mechanizm infekcji wirusem Zika w mózgu zarówno we wczesnym, jak i późniejszym etapie rozwoju, a także w stadium dorosłym. Główną zaletą tej techniki jest to, że można łatwo osiągnąć kierunek infekcji mózgu.

Implikacje tej techniki rozciągają się na terapie lub diagnozy małogłowia wywołanego wirusem Zika lub innych zaburzeń neurorozwojowych. Chociaż metoda ta może dostarczyć informacji na temat patogenezy wirusa Zika, może być również stosowana do badania innych infekcji flawiwirusowych w mózgu, takich jak wirus dengi. Tuż przed zabiegiem należy załadować mieszankę do wstrzykiwań wirusa Zika do przygotowanej szklanej igły iniekcyjnej, najpierw montując gazoszczelną nasadkę Luer-lock i rurkę do wstrzykiwań o pojemności 50 mikrolitrów.

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