Intranasally delivered colostrum-derived small extracellular vesicles mitigate acute neuroinflammation in periventricular leukomalacia

[Display omitted] •This article demonstrates that intranasally delivered colostrum-derived sEVs can reach the neonatal brain.•The results suggest that colostrum sEVs mitigate PVL-like injury and show promise for neonatal brain injury.•Intranasal sEV delivery has potential as a non-invasive translati...

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Published in:Brain research Vol. 1870; p. 150041
Main Authors: Ture, Beyza, Erdogan, Funda, Armagan, Coskun, Tastan, Bora, Gonul, Ceren Perihan, Guducu, Yusuf, Akyildiz, Can, Duman, Nuray, Genc, Sermin, Ozkan, Hasan
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.01.2026
Subjects:
Colostrum
Intranasal Administration
Neurology
Neurorestoration
Periventricular Leukomalacia
Preterm Infants
small Extracellular Vesicles
CC
PBS
BCA
RT
BBB
EVs
Neurorestoration
PVL
Periventricular Leukomalacia
WB
EDTA
ROI
LPS
S.E.M
Intranasal Administration
BSA
FBS
small Extracellular Vesicles
Preterm Infants
NTA
sEVs
Colostrum
IF
Extracellular Vesicles
Blood-brain barrier
Region of interest
Lipopolysaccharide
Nanoparticle Tracking Analysis
Fetal Bovine Serum
Standard Error of the Mean
Bicinchoninic Acid
Corpus callosum
Phosphate-buffered Saline
Western Blot
Room Temperature
Bovine Serum Albumin
Immunofluorescence
Ethylenediaminetetraacetic Acid
ISSN:0006-8993, 1872-6240, 1872-6240
Online Access:Get full text
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Summary:[Display omitted] •This article demonstrates that intranasally delivered colostrum-derived sEVs can reach the neonatal brain.•The results suggest that colostrum sEVs mitigate PVL-like injury and show promise for neonatal brain injury.•Intranasal sEV delivery has potential as a non-invasive translational strategy, for neonatal white-matter injury. Periventricular leukomalacia (PVL) is a predominant white matter injury in preterm infants, leading to lifelong neurodevelopmental disability, and yet disease-modifying therapies are lacking. Breast milk, especially colostrum, contains bioactive components with potential neuroprotective properties, among which extracellular vesicles (EVs) have recently attracted increasing attention. This study aimed to evaluate the neurorestorative efficacy of intranasally administered colostrum-derived small EVs (sEVs) in a lipopolysaccharide (LPS)-induced PVL model. sEVs were isolated from Sprague-Dawley rats’ colostrum and characterized by Nanoparticle Tracking Analysis (NTA) and Western blot (WB). To assess brain delivery following intranasal administration, sEVs were labeled with PKH67. Neonatal pups were randomly assigned to three groups: control, systemic LPS, and LPS + sEVs. A PVL-like model was induced (LPS) injection at postnatal day 5 (P5), and intranasal sEVs were administered thereafter. Brains were analyzed at P11. Labeled sEVs were detectable in the hippocampus and corpus callosum (CC) within 3 h of intranasal delivery. LPS increased microglial and astroglial markers (Iba1, GFAP) and reduced neuronal/Oligodendroglial markers (NeuN, Olig2), whereas sEVs treatment partially normalized these indices in both regions. Colostrum-derived sEVs reach the neonatal brain via the intranasal route and mitigate LPS-induced neuroinflammatory changes. These findings support intranasal sEVs as a non-invasive candidate approach for neonatal white-matter injury. To our knowledge, this is the first demonstration that intranasally delivered colostrum-derived sEVs can penetrate the neonatal brain and ameliorate histological indices of PVL-like injury, suggesting that this approach could be a novel and promising treatment strategy for neonatal brain injury.
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ISSN:0006-8993
1872-6240
1872-6240
DOI:10.1016/j.brainres.2025.150041