Understanding the pathophysiology of acute critical illness: translational lessons from zebrafish models

Intensive Care Medicine Experimental, 2024 · DOI: https://doi.org/10.1186/s40635-024-00595-x · Published: January 10, 2024

Critical Care Research Methodology & Design Regenerative Medicine & Stem Cells

Simple Explanation

Zebrafish are valuable for studying acute critical illness because they share extensive genomic homology with humans; more than 80% of human genes associated with diseases are conserved in zebrafish. Zebrafish have the ability to regenerate complex structures such as fins, heart, brain, retina, and other organs. Zebrafish research excels in revealing conserved biological pathways and mechanisms, enhancing our understanding of human biology and diseases.

Study Duration

Not specified

Participants

Zebrafish

Evidence Level

Review

Key Findings

1
LPS-induced zebrafish endotoxemia results in extravascular migration of neutrophils and macrophages and changes in the expression of tight junction proteins.
2
Knockdown of caspy2, which has the highest homology to human caspase-4/5, resulted in a higher survival rate in comparison to the control group in zebrafish sepsis models.
3
In spinal cord injury (SCI) models, localized EMT was revealed to be the key factor in spinal cord regeneration.

Research Summary

This review summarizes translational research using zebrafish to study sepsis, organ failure, and trauma, highlighting technologies applicable in this model organism. Zebrafish models allow visualization of lipopolysaccharide (LPS)-induced vascular leakage and changes in cellular junction protein expression in sepsis studies. Zebrafish studies have identified key genes and pathways involved in regeneration, such as ctgfa in spinal cord repair and klf1 in myocardial regeneration.

Practical Implications

Drug Discovery

Zebrafish models can be used for high-throughput drug discovery for sepsis and other acute critical illnesses.

Therapeutic Targets

Identification of key genes and pathways, like ctgfa and klf1, can lead to the development of targeted therapies for organ regeneration.

Understanding Pathophysiology

Zebrafish models help in understanding the underlying biological basis of pathological processes in mechanistic detail, aiding in the development of better treatments.

Study Limitations

1
Zebrafish models may not fully replicate the complexity of mammalian systems.
2
Findings in zebrafish need to be validated in mammalian models and human studies.
3
There may be differences in gene function and signaling pathways between zebrafish and humans.

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