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Published on: November 20, 2015
Acquired Brain Injuries Across the Perinatal Spectrum: Pathophysiology and Emerging Therapies
Jeffrey B Russ1, Bridget E L Ostrem2
1Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
Insights
Acquired perinatal brain insults disrupt central nervous system development. Emerging therapies show promise for treating these conditions and improving neurodevelopmental outcomes in newborns.
Area of Science:
- Neuroscience
- Developmental Biology
- Perinatal Medicine
Background:
- Acquired factors like infections, inflammation, hypoxia, and toxins disrupt fetal central nervous system development.
- External influences such as placental health, maternal health, and environmental exposures also impact neurodevelopment.
- Perinatal brain insults affect development in a stage-specific manner, depending on cellular and process susceptibility.
Purpose of the Study:
- To review the pathophysiology, neurodevelopmental outcomes, and management of acquired perinatal brain conditions.
- To categorize insults in the fetal brain by trimester and postnatal brain by gestational age at birth.
- To highlight emerging therapies for acquired perinatal brain disorders.
Main Methods:
- Review of existing literature on acquired perinatal brain insults.
- Categorization of fetal brain insults by trimester.
- Focus on common postnatal pathologies like white matter injury, germinal matrix hemorrhage/intraventricular hemorrhage, and hypoxic-ischemic encephalopathy.
Main Results:
- Acquired insults cause stage-specific disruptions in central nervous system development.
- Common conditions include white matter injury, germinal matrix hemorrhage/intraventricular hemorrhage in preterm infants, and hypoxic-ischemic encephalopathy in term infants.
- Current treatments are limited, but preclinical and early clinical therapies are advancing.
Conclusions:
- Acquired perinatal brain insults pose significant risks to neurodevelopment.
- Understanding the stage-specific nature of these insults is crucial for management.
- Emerging cell type- and stage-specific therapies offer hope for improved treatment and mitigation of neurodevelopmental consequences.
Abstract:
The development of the central nervous system can be directly disrupted by a variety of acquired factors, including infectious, inflammatory, hypoxic-ischemic, and toxic insults. Influences external to the fetus also impact neurodevelopment, including placental health, maternal comorbidities, adverse experiences, environmental exposures, and social determinants of health. Acquired perinatal brain insults tend to affect the developing brain in a stage-specific manner that reflects the susceptible cell types, developmental processes, and risk factors present at the time of the insult. In this review, we discuss the pathophysiology, neurodevelopmental outcomes, and management of common acquired perinatal brain conditions. In the fetal brain, we divide insults based on trimester, and in the postnatal brain, we focus on common pathologies that have a presentation dependent on gestational age at birth: white matter injury and germinal matrix hemorrhage/intraventricular hemorrhage in preterm infants and hypoxic-ischemic encephalopathy in term infants. Although specific treatments for fetal and newborn brain disorders are currently limited, we emphasize therapies in preclinical or early clinical phases of the development pipeline. The growing number of novel cell type- and stage-specific emerging therapies suggests that in the near future we may have a dramatically improved ability to treat acquired perinatal brain disorders and to mitigate the associated neurodevelopmental consequences.
