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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Perinatal neuroprotection
Kirsten E Salmeen1, Angie C Jelin2, Mari-Paule Thiet3
1513 Parnassus Avenue, Room HSE-1634, Box 0556, San Francisco, CA 94143-0556 USA.
Insights
Perinatal neuroprotection strategies like magnesium sulfate and hypothermia show promise for preventing newborn brain injury. However, significant challenges remain in reducing preterm birth and repairing existing brain damage.
Area of Science:
- Neonatal neurology
- Perinatal medicine
- Neuroscience
Background:
- Fetal and neonatal brain injury can lead to lifelong neurological disabilities.
- Prematurity is a major risk factor, but full-term infants account for the majority of affected children.
- Current research focuses on neuroprotection to mitigate perinatal brain injury.
Purpose of the Study:
- To review current strategies for perinatal neuroprotection.
- To identify promising agents and preventative measures.
- To highlight existing challenges and future research directions.
Main Methods:
- Review of established and emerging neuroprotective interventions.
- Analysis of preventative strategies for preterm and term infants.
- Examination of agents for neuronal repair and post-injury modulation.
Main Results:
- Magnesium sulfate and therapeutic hypothermia are established neuroprotective measures.
- Umbilical cord blood, erythropoietin, delayed cord clamping, progesterone, and infection avoidance show promise.
- Challenges include reducing preterm birth rates and predicting/treating hypoxic injury in term infants.
Conclusions:
- Despite advances in perinatal neuroprotection, significant challenges persist.
- Further research is needed to improve prevention and repair of neonatal brain injury.
- Perinatal brain injury continues to affect thousands of newborns annually, causing substantial morbidity and mortality.
Abstract:
Fetal or neonatal brain injury can result in lifelong neurologic disability. The most significant risk factor for perinatal brain injury is prematurity; however, in absolute numbers, full-term infants represent the majority of affected children. Research on strategies to prevent or mitigate the impact of perinatal brain injury ("perinatal neuroprotection") has established the mitigating roles of magnesium sulfate administration for preterm infants and therapeutic hypothermia for term infants with suspected perinatal brain injury. Banked umbilical cord blood, erythropoietin, and a number of other agents that may improve neuronal repair show promise for improving outcomes following perinatal brain injury in animal models. Other preventative strategies include delayed umbilical cord clamping in preterm infants and progesterone in women with prior preterm birth or short cervix and avoidance of infections. Despite these advances, we have not successfully decreased the rate of preterm birth, nor are we able to predict term infants at risk of hypoxic brain injury in order to intervene prior to the hypoxic event. Further, we lack the ability to modulate the sequelae of neuronal cell insults or the ability to repair brain injury after it has been sustained. As a consequence, despite exciting advances in the field of perinatal neuroprotection, perinatal brain injury still impacts thousands of newborns each year with significant long-term morbidity and mortality.
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