Related Experiment Video
Updated: Jul 19, 2026
Hypoxia Alters miRNAs Levels Involved in Non-Mendelian Inheritance of Autism Spectrum Disorder in Mice
Published on: July 11, 2025
Hyperoxic exposure leads to nitrative stress and ensuing microvascular degeneration and diminished brain mass and
Mirna Sirinyan1, Florian Sennlaub, Allison Dorfman
1Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Insights
High oxygen exposure in premature infants causes brain damage by altering nitric oxide (NO) and antioxidant systems, leading to impaired brain development and function.
Area of Science:
- Neuroscience
- Neonatal Research
- Vascular Biology
Background:
- Preterm infants surviving birth often experience cognitive impairments.
- Postnatal hyperoxia (high oxygen) is a common factor in premature infants, known to damage lungs and retinas.
- Limited data exist on hyperoxia's effects on the developing brain.
Purpose of the Study:
- To investigate the impact of hyperoxia on the brain tissue of immature subjects.
- To elucidate the mechanisms underlying hyperoxia-induced brain injury in neonates.
Main Methods:
- Rat pups were exposed to either 21% or 80% oxygen from birth to day 6.
- Cerebral vascular density was assessed using lectin immunohistochemistry.
- Protein levels were analyzed via immunoblots, and cerebral function was evaluated using visual evoked potentials.
Main Results:
- Hyperoxia exposure resulted in cerebral microvascular degeneration, reduced brain mass, and functional deficits.
- Key molecular changes included increased endothelial nitric oxide synthase (eNOS) and decreased Cu/Zn superoxide dismutase (SOD).
- An imbalance favoring nitrating agents (e.g., nitrotyrosine) was observed, alongside decreased NF-kappaB and vascular endothelial growth factor receptor 2 (VEGFR2).
Conclusions:
- Nitric oxide (NO) and nitrating agents are identified as primary mediators of hyperoxia-induced cerebral microvascular damage.
- This damage leads to impaired brain development and function in immature subjects exposed to high oxygen.
- Interventions targeting NO pathways and antioxidant defenses (e.g., NOS inhibitors, SOD mimetics) showed protective effects.
Background And Purpose:
Neonates that survive very preterm birth have a high prevalence of cognitive impairment in later life. A common factor detected in premature infants is their postnatal exposure to high oxygen tension relative to that in utero. Hyperoxia is known to elicit injury to premature lung and retina. Because data on the exposure of the brain to hyperoxia are limited, we studied the effects of high oxygen on this tissue.
Methods:
Rat pups were exposed from birth until day 6 to 21% or 80% O(2). Cerebral vascular density was quantified by lectin immunohistochemistry. Immunoblots for several proteins were performed on brain extracts. We assessed cerebral functional deficits by visual evoked potentials.
Results:
Exposure of pups to hyperoxia leads to cerebral microvascular degeneration, diminished brain mass, and cerebral functional deficits. These effects are preceded by an upregulation of endothelial nitric oxide synthase (eNOS) in cerebral capillaries and a downregulation of Cu/Zn superoxide dismutase (SOD). The imbalance in nitric oxide (NO) production and antioxidant defenses favors the formation of nitrating agents in the microvessels revealed by increased nitrotyrosine (3-nt) immunoreactivity and decreased expression of NF-kappaB and the dependent vascular endothelial growth factor receptor 2. NOS inhibitors and eNOS deletion as well as an SOD mimetic (CuDIPS) restore vascular endothelial growth factor receptor-2 levels and nearly abolish the vasoobliteration. NOS inhibitors and SOD mimetic also prevent O(2)-induced diminished brain mass and functional deficit.
Conclusions:
Data identify NO and nitrating agents as major mediators of cerebral microvascular damage, ensuing impaired brain development and function in immature subjects exposed to hyperoxia.
