A Scalable Model to Study the Effects of Blunt-Force Injury in Adult Zebrafish

James Hentig; Kaylee Cloghessy; Chloe Dunseath; David  R. Hyde

doi:10.3791/62709

A Scalable Model to Study the Effects of Blunt-Force Injury in Adult Zebrafish

JoVE Journal
Neuroscience

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JoVE Journal Neuroscience

A Scalable Model to Study the Effects of Blunt-Force Injury in Adult Zebrafish

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08:13 min

May 31, 2021

DOI: 10.3791/62709-v

James Hentig^1,2,3, Kaylee Cloghessy^1,2,3, Chloe Dunseath^2,3, David R. Hyde^1,2,3

¹Department of Biological Sciences,University of Notre Dame, ²Center for Zebrafish Research,University of Notre Dame, ³Center for Stem Cells and Regenerative Medicine,University of Notre Dame

Overview

This study presents a modified Marmarou weight drop model for inducing blunt-force traumatic brain injury (TBI) in adult zebrafish. The research investigates a range of pathologies that follow TBI and explores the mechanisms of neuronal regeneration in response to varying severities of injury.

Key Study Components

Area of Science

Neuroscience
Traumatic brain injury
Zebrafish model

Background

Adult zebrafish serve as a relevant model for studying human TBI.
The Marmarou weight drop model induces controlled, reproducible injuries.
Investigation focuses on injury heterogeneity and regeneration mechanisms.
Different injury severities lead to distinct biological responses.

Purpose of Study

Examine the pathologies following blunt-force TBI in zebrafish.
Investigate the mechanisms underlying neuronal regeneration post-injury.
Assess injury characteristics and recovery responses linked to varying TBI severities.

Methods Used

The study utilizes a zebrafish model to induce blunt-force TBI.
Injuries are scaled to be mild, moderate, or severe using a weight drop mechanism.
Post-injury, biological responses and cellular dynamics are monitored.
Specific timelines for recovery and assessment of brain injuries are included.
Dissection and observation of brain morphology and cell proliferation were performed.

Main Results

Findings indicate robust neurogenic responses post-TBI in various brain regions.
Vascular injury was noted as a prominent response, especially in different fish strains.
Cell proliferation marked by EdU labeling was significantly increased in injured animals.
Moderate and severe TBI showed distinct edema patterns, with recovery observed by 5 dpi.

Conclusions

This study demonstrates a scalable model for studying TBI and recovery in zebrafish.
The insights gained enhance understanding of neuronal regeneration mechanisms following injury.
Findings may provide a basis for future research into therapeutic strategies for TBI.

Frequently Asked Questions

What are the advantages of using zebrafish as a model for TBI?

Zebrafish possess rapid development, transparency, and regenerative capabilities, making them ideal for studying brain injuries and regeneration.

How is the blunt-force TBI induced in zebrafish?

A weight is dropped onto a steel plate positioned on the fish's head, allowing for varying injury severities depending on the weight and drop height.

What types of biological responses are measured after TBI?

The study measures neurogenic response, vascular injury, and edema, as well as cell proliferation in various brain regions following injury.

Can this method be applied to other models or injuries?

Yes, the principles of this method may be adapted for other animal models or types of mechanical injuries, providing flexibility in research applications.

What are the limitations of the zebrafish TBI model?

While zebrafish provide valuable insights, differences between fish and mammalian brain structures may limit direct comparisons to human TBI responses.

We modified the Marmarou weight drop model for adult zebrafish to examine a breadth of pathologies following blunt-force traumatic brain injury (TBI) and the mechanisms underlying subsequent neuronal regeneration. This blunt-force TBI model is scalable, induces a mild, moderate, or severe TBI, and recapitulates injury heterogeneity observed in human TBI.

This protocol provides a simple, rapid, and reproducible method to induce a scalable blunt force traumatic brain injury in adult zebrafish. The adult zebrafish that undergo this blunt force traumatic brain injury exhibit many of the characteristics observed in humans that suffer from a blunt force TBI. Demonstrating the procedure will be Mr.James Hentig and Ms.Kaylee Cloghessy, two doctoral students from my laboratory.

Begin by filling a Petri dish with modeling clay. Then use fingers or the back of a pair of forceps to create a raised platform with additional modeling clay. Divide the raised platform lengthwise into two approximately equal halves using a razor blade.

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