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Updated: Jan 11, 2026
Mouse Models of Periventricular Leukomalacia
Published on: May 18, 2010
Intranasally delivered colostrum-derived small extracellular vesicles mitigate acute neuroinflammation in
Beyza Ture1, Funda Erdogan2, Coskun Armagan2
1Izmir Biomedicine and Genome Center, Izmir, Turkiye; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkiye.
Insights
Intranasal administration of colostrum-derived extracellular vesicles (EVs) successfully delivered to the neonatal brain, mitigating white matter injury in a rat model. This offers a promising non-invasive treatment for neonatal brain injury.
Area of Science:
- Neonatal Neurology
- Extracellular Vesicle Biology
- Neuroprotection
Background:
- Periventricular leukomalacia (PVL) is a major cause of neurodevelopmental disability in preterm infants, with limited treatment options.
- Breast milk contains bioactive components, including extracellular vesicles (EVs), with potential neuroprotective effects.
- Small extracellular vesicles (sEVs) derived from colostrum are being investigated for therapeutic potential.
Purpose of the Study:
- To evaluate the neurorestorative efficacy of intranasally administered colostrum-derived small EVs (sEVs).
- To assess the brain delivery and therapeutic effects of sEVs in a lipopolysaccharide (LPS)-induced periventricular leukomalacia (PVL) model in neonatal rats.
Main Methods:
- sEVs were isolated from rat colostrum and characterized.
- A PVL-like model was induced using LPS in neonatal rats.
- Intranasal administration of PKH67-labeled sEVs was performed, followed by brain analysis at postnatal day 11.
Main Results:
- Labeled sEVs were detected in the neonatal rat brain (hippocampus and corpus callosum) within 3 hours of intranasal administration.
- LPS-induced PVL model showed increased microglial and astroglial markers and decreased neuronal/oligodendroglial markers.
- sEVs treatment partially normalized these cellular and molecular changes in the brain.
Conclusions:
- Intranasal administration of colostrum-derived sEVs effectively delivers them to the neonatal brain.
- sEVs mitigate LPS-induced neuroinflammatory and cellular changes associated with PVL.
- Intranasal sEVs represent a promising, non-invasive therapeutic strategy for neonatal white matter injury.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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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