Exosomes populate the cerebrospinal fluid of preterm infants with post-haemorrhagic hydrocephalus

Robert Spaull; Bryony McPherson; Andriana Gialeli; Aled Clayton; James Uney; Axel Heep; Óscar Cordero-Llana

doi:10.1016/j.ijdevneu.2019.01.004

Exosomes populate the cerebrospinal fluid of preterm infants with post-haemorrhagic hydrocephalus

Robert Spaull, Bryony McPherson, Andriana Gialeli, Aled Clayton, James Uney, Axel Heep^*, Óscar Cordero-Llana

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Background
Preterm infants are at risk of germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) which leads to post-haemorrhagic hydrocephalus (PHH) in 30% of infants; this is associated with moderate-severe neurodevelopmental impairment and confers significant risk of cerebral palsy. There are however no predictive indicators of the severity or long-term outcome after GMH-IVH. In recent years, endosome-derived extracellular vesicles (EVs) or exosomes have been isolated from biofluids and shown to mediate intercellular communication via selective enrichment in proteins and micro-RNAs.
Methods
This study aimed to isolate and characterise EVs from the cerebrospinal fluid (CSF) of 3 preterm infants with PHH using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) with immunogold protein labelling, and micro-RNA analysis.
Results
NTA of unaltered CSF revealed a heterogeneous and dynamic population of EVs. Exosomal-sized EVs were isolated by differential ultracentrifugation and TEM confirmed the presence of CD63+ and CD81+ exosomes. The micro-RNAs miR-9, miR-17, miR-26a, miR-124 and miR-1911 were detected within the exosome-enriched fraction and profiled over time.
Conclusion
This is the first reported characterisation of exosomes from the CSF of preterm infants with post-haemorrhagic hydrocephalus.

Original language	English
Pages (from-to)	59-65
Number of pages	7
Journal	International Journal of Developmental Neuroscience
Volume	73
Early online date	9 Jan 2019
DOIs	https://doi.org/10.1016/j.ijdevneu.2019.01.004
Publication status	Published - Apr 2019

Keywords

Cerebral palsy
Cerebrospinal fluid
Exosome
Intraventricular hemorrhage
Micro RNA
Preterm infant

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10.1016/j.ijdevneu.2019.01.004

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Accepted author manuscript, 1.06 MBLicence: CC BY-NC-ND

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@article{b274fc7f4154494480c7c89b19106501,

title = "Exosomes populate the cerebrospinal fluid of preterm infants with post-haemorrhagic hydrocephalus",

abstract = "BackgroundPreterm infants are at risk of germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) which leads to post-haemorrhagic hydrocephalus (PHH) in 30% of infants; this is associated with moderate-severe neurodevelopmental impairment and confers significant risk of cerebral palsy. There are however no predictive indicators of the severity or long-term outcome after GMH-IVH. In recent years, endosome-derived extracellular vesicles (EVs) or exosomes have been isolated from biofluids and shown to mediate intercellular communication via selective enrichment in proteins and micro-RNAs. MethodsThis study aimed to isolate and characterise EVs from the cerebrospinal fluid (CSF) of 3 preterm infants with PHH using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) with immunogold protein labelling, and micro-RNA analysis.ResultsNTA of unaltered CSF revealed a heterogeneous and dynamic population of EVs. Exosomal-sized EVs were isolated by differential ultracentrifugation and TEM confirmed the presence of CD63+ and CD81+ exosomes. The micro-RNAs miR-9, miR-17, miR-26a, miR-124 and miR-1911 were detected within the exosome-enriched fraction and profiled over time.ConclusionThis is the first reported characterisation of exosomes from the CSF of preterm infants with post-haemorrhagic hydrocephalus. ",

keywords = "Cerebral palsy, Cerebrospinal fluid, Exosome, Intraventricular hemorrhage, Micro RNA, Preterm infant",

author = "Robert Spaull and Bryony McPherson and Andriana Gialeli and Aled Clayton and James Uney and Axel Heep and {\'O}scar Cordero-Llana",

year = "2019",

month = apr,

doi = "10.1016/j.ijdevneu.2019.01.004",

language = "English",

volume = "73",

pages = "59--65",

journal = "International Journal of Developmental Neuroscience",

issn = "0736-5748",

publisher = "Elsevier",

}

TY - JOUR

T1 - Exosomes populate the cerebrospinal fluid of preterm infants with post-haemorrhagic hydrocephalus

AU - Spaull, Robert

AU - McPherson, Bryony

AU - Gialeli, Andriana

AU - Clayton, Aled

AU - Uney, James

AU - Heep, Axel

AU - Cordero-Llana, Óscar

PY - 2019/4

Y1 - 2019/4

N2 - BackgroundPreterm infants are at risk of germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) which leads to post-haemorrhagic hydrocephalus (PHH) in 30% of infants; this is associated with moderate-severe neurodevelopmental impairment and confers significant risk of cerebral palsy. There are however no predictive indicators of the severity or long-term outcome after GMH-IVH. In recent years, endosome-derived extracellular vesicles (EVs) or exosomes have been isolated from biofluids and shown to mediate intercellular communication via selective enrichment in proteins and micro-RNAs. MethodsThis study aimed to isolate and characterise EVs from the cerebrospinal fluid (CSF) of 3 preterm infants with PHH using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) with immunogold protein labelling, and micro-RNA analysis.ResultsNTA of unaltered CSF revealed a heterogeneous and dynamic population of EVs. Exosomal-sized EVs were isolated by differential ultracentrifugation and TEM confirmed the presence of CD63+ and CD81+ exosomes. The micro-RNAs miR-9, miR-17, miR-26a, miR-124 and miR-1911 were detected within the exosome-enriched fraction and profiled over time.ConclusionThis is the first reported characterisation of exosomes from the CSF of preterm infants with post-haemorrhagic hydrocephalus.

AB - BackgroundPreterm infants are at risk of germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) which leads to post-haemorrhagic hydrocephalus (PHH) in 30% of infants; this is associated with moderate-severe neurodevelopmental impairment and confers significant risk of cerebral palsy. There are however no predictive indicators of the severity or long-term outcome after GMH-IVH. In recent years, endosome-derived extracellular vesicles (EVs) or exosomes have been isolated from biofluids and shown to mediate intercellular communication via selective enrichment in proteins and micro-RNAs. MethodsThis study aimed to isolate and characterise EVs from the cerebrospinal fluid (CSF) of 3 preterm infants with PHH using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) with immunogold protein labelling, and micro-RNA analysis.ResultsNTA of unaltered CSF revealed a heterogeneous and dynamic population of EVs. Exosomal-sized EVs were isolated by differential ultracentrifugation and TEM confirmed the presence of CD63+ and CD81+ exosomes. The micro-RNAs miR-9, miR-17, miR-26a, miR-124 and miR-1911 were detected within the exosome-enriched fraction and profiled over time.ConclusionThis is the first reported characterisation of exosomes from the CSF of preterm infants with post-haemorrhagic hydrocephalus.

KW - Cerebral palsy

KW - Cerebrospinal fluid

KW - Exosome

KW - Intraventricular hemorrhage

KW - Micro RNA

KW - Preterm infant

UR - http://www.scopus.com/inward/record.url?scp=85059801741&partnerID=8YFLogxK

U2 - 10.1016/j.ijdevneu.2019.01.004

DO - 10.1016/j.ijdevneu.2019.01.004

M3 - Article (Academic Journal)

C2 - 30639393

AN - SCOPUS:85059801741

SN - 0736-5748

VL - 73

SP - 59

EP - 65

JO - International Journal of Developmental Neuroscience

JF - International Journal of Developmental Neuroscience

ER -

Exosomes populate the cerebrospinal fluid of preterm infants with post-haemorrhagic hydrocephalus

Abstract

Keywords

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Characteristics of exosomes in the cerebrospinal fluid of preterm infants

Nanomolecular signalling in the developing brain: Characteristics of exosomes in the cerebrospinal fluid of preterm infants

Elizabeth Blackwell Institute Clinical Primer

Dr Oscar Cordero Llana

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Exosomes populate the cerebrospinal fluid of preterm infants with post-haemorrhagic hydrocephalus

Abstract

Keywords

Access to Document

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Research output

Characteristics of exosomes in the cerebrospinal fluid of preterm infants

Nanomolecular signalling in the developing brain: Characteristics of exosomes in the cerebrospinal fluid of preterm infants

Prizes

Elizabeth Blackwell Institute Clinical Primer

Profiles

Dr Oscar Cordero Llana

Cite this