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

JoVE Journal
Neuroscience

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JoVE Journal Neuroscience

Modeling Neonatal Intraventricular Hemorrhage Through Intraventricular Injection of Hemoglobin

ヘモグロビンの脳室内注射による新生児脳室内出血のモデリング

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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.

ラットの仔を用いた新生児脳室内出血のモデルを提示し、ヒトに見られる病態を模倣した。

このプロトコルは、IVH誘発性脳損傷と水頭症の臨床的に関連するモデルを開発し、心室へのヘモグロビン注射を利用して、新しい治療戦略をテストするための心室容積のその後の定量を可能にするため、重要です。この技術の主な利点は、ヘモグロビンおよび鉄経路血液分解産物によって特異的に媒介されるIVHの病理学の研究を可能にすることである。この手法も使いやすく、用途が広いです。

この技術の意味は、IVHの病態生理学のさらなる理解と、IVH後の神経学的後遺症の予防のための臨床的に関連する治療戦略の評価を可能にするため、出血後水頭症の治療法の開発にまで及びます。手順を実演するのは、オーストラリア研究所のアソシエイトポスドクであるスルティラマギリです。まず、麻酔をかけたラットを定位装置に入れ、鼻を麻酔アダプターに配置します。

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