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Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy
Published on: October 28, 2022
New antioxidant drugs for neonatal brain injury
Maria Luisa Tataranno1, Serafina Perrone1, Mariangela Longini1
1Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Insights
Brain injuries in newborns stem from various factors, increasing vulnerability to oxidative stress. Early identification of high-risk infants is crucial for targeted antioxidant therapy to prevent long-term neurodevelopmental impairment.
Area of Science:
- Neonatal neurology
- Neuroscience
- Developmental pediatrics
Background:
- Brain injury in newborns is heterogeneous, with diverse etiologies including genetic, metabolic, and infectious factors.
- Immature brains are highly susceptible to oxidative stress due to limited antioxidant capacity and high free radical generation.
- Oxidative stress contributes to neuronal damage and neurodevelopmental impairment through mechanisms like impaired enzyme activity and excitotoxicity.
Purpose of the Study:
- To review the mechanisms of oxidative brain injury in newborns.
- To discuss the potential of neuroprotective interventions targeting the oxidative stress cascade.
- To highlight the challenges and future directions for antioxidant therapy in neonatal brain injury.
Main Methods:
- Literature review of mechanisms underlying neonatal brain injury.
- Analysis of the role of oxidative stress and free radicals in brain damage.
- Evaluation of current and potential neuroprotective strategies, including antioxidant therapies.
Main Results:
- Free radicals impair Na+/K+-ATPase activity, leading to excitotoxicity and neuronal cell death.
- Excess free iron and impaired iron metabolism exacerbate oxidative stress in newborns.
- Current antioxidant therapies initiated post-resuscitation show uncertain clinical benefits.
Conclusions:
- Targeting oxidative stress pathways offers potential for neuroprotection in neonatal brain injury.
- Early identification of at-risk infants is essential for effective and safe antioxidant interventions.
- Future research should focus on developing safe, targeted antioxidant therapies combined with standard treatments to prevent long-term neurodevelopmental deficits.
Abstract:
The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs) generation in rapidly growing tissue. FRs impair transmembrane enzyme Na(+)/K(+)-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment.
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