Modeling Neonatal Intraventricular Hemorrhage Through Intraventricular Injection of Hemoglobin

Brandon A. Miller; Shelei Pan; Peter H. Yang; Catherine Wang; Amanda L. Trout; Dakota DeFreitas; Sruthi Ramagiri; Scott D. Olson; Jennifer M. Strahle

doi:10.3791/63345

Modelagem da Hemorragia Intraventricular Neonatal Através da Injeção Intraventricular de Hemoglobina

JoVE Journal
Neuroscience

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JoVE Journal Neuroscience

Modeling Neonatal Intraventricular Hemorrhage Through Intraventricular Injection of Hemoglobin

Modelagem da Hemorragia Intraventricular Neonatal Através da Injeção Intraventricular de Hemoglobina

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07:57 min

August 25, 2022

DOI: 10.3791/63345-v

Brandon A. Miller^1,2, Shelei Pan³, Peter H. Yang³, Catherine Wang¹, Amanda L. Trout¹, Dakota DeFreitas³, Sruthi Ramagiri³, Scott D. Olson², Jennifer M. Strahle^3,4,5

¹Department of Neurosurgery,University of Kentucky, ²Department of Pediatric Surgery,University of Texas, ³Department of Neurological Surgery,Washington University in St. Louis School of Medicine, ⁴Department of Orthopedic Surgery,Washington University in St. Louis School of Medicine, ⁵Department of Pediatrics,Washington University in St. Louis School of Medicine

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Overview

This study presents a clinically relevant model for neonatal intraventricular hemorrhage (IVH) using rat pups. The introduction of hemoglobin into the ventricles mimics human pathology and allows for the evaluation of therapeutic strategies aimed at post-hemorrhagic hydrocephalus.

Key Study Components

Area of Science

Neuroscience
Neonatal brain injury
Modeling hydrocephalus

Background

Intraventricular hemorrhage (IVH) is a significant cause of neurological issues in neonates.
Current models lack the specificity to study the effects of hemoglobin and iron breakdown products.
Understanding IVH pathophysiology is critical for developing therapeutic interventions.
This study aims to fill the gap in modeling the pathology of IVH.

Purpose of Study

To develop a rat model of IVH that mimics the human condition.
To evaluate the impact of hemoglobin on ventricle size and its inflammatory effects.
To provide a platform for testing new therapies for IVH-related complications.

Methods Used

The protocol involves the stereotactic injection of hemoglobin into neonate rat ventricles.
Rat pups are anesthetized, and a 0.3 cm incision is made to access the skull for injection.
Post-injection MRI is utilized to assess brain changes over specific timeframes.
Measurements include ventricle volumes, inflammatory responses, and astrocyte activation.

Main Results

Hemoglobin injection resulted in significant ventriculomegaly and inflammatory cytokine elevation.
Astrocyte activation was notably higher in hemoglobin-injected pups compared to controls.
Differences in lateral ventricle volumes between treatment groups were observed over time.

Conclusions

This study presents a valuable model for investigating treatments for IVH and its complications.
The findings enhance understanding of IVH pathophysiology and the impact of hemoglobin.
Insights gained could lead to improved therapeutic strategies for neurological outcomes following IVH.

Frequently Asked Questions

What are the advantages of this model for studying IVH?

The model effectively mimics the human pathology of IVH, specifically the impact of hemoglobin breakdown products, making it relevant for therapeutic studies.

How is the hemoglobin injection administered?

Hemoglobin is injected into the lateral ventricles of anesthetized rat pups using a stereotactic apparatus, allowing precise delivery.

What outcomes are measured following the injection?

MRI scans are used to assess ventricular sizes, inflammatory markers, and astrocyte activation in the brain.

Can this method be adapted for other studies?

Yes, the technique allows for further investigations into CSF flow and its alterations stemming from IVH.

What are key limitations in this study?

The main limitation could be the long-term effects of hemoglobin on brain development and functionality, which needs further investigation.

What types of data can be obtained?

Data on ventricle volume changes, inflammatory responses, and astrocyte activity can be obtained through MRI and biochemical assays.

How long should monitoring after injection be conducted?

Monitoring should be conducted for at least 38 days post-injection to assess the long-term effects on ventricular size and inflammation.

Apresentamos um modelo de hemorragia intraventricular neonatal utilizando filhotes de ratos que mimetiza a patologia observada em humanos.

Esse protocolo é significativo porque desenvolvemos um modelo clinicamente relevante de lesão cerebral induzida por IVH e hidrocefalia, utilizando injeção de hemoglobina nos ventrículos, o que permite a posterior quantificação dos volumes ventrículos na aplicação, para testar novas estratégias terapêuticas. A principal vantagem desta técnica é que ela permite o estudo da patologia da IVH que é especificamente mediada por hemoglobina e produtos de degradação do sangue da via de ferro. Esta técnica também é fácil de usar e versátil.

As implicações dessa técnica se estendem para o desenvolvimento de terapias para hidrocefalia pós-hemorrágica, pois permite uma maior compreensão da fisiopatologia da IVH e a valorização de estratégias de tratamento clinicamente relevantes para a prevenção de sequelas neurológicas após IVH. Demonstrando o procedimento estará Sruthi Ramagiri, um Pós-Doutor Associado do Laboratório da Austrália. Para iniciar coloque o rato anestesiado propenso no aparelho estereotáxico com o nariz posicionado no adaptador anestésico.

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