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Published on: March 2, 2018
Human neocortical development as a basis to understand mechanisms underlying neurodevelopmental disabilities in
Ken-Ichiro Kubo1,2, Kimiko Deguchi1,3
1Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
Insights
Extremely preterm infants face neurodevelopmental disabilities due to brain injuries affecting neocortex development, including neurogenesis and neuronal migration. Improved maternal and neonatal care is crucial for better long-term outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Neonatal Medicine
Background:
- Advances in perinatal medicine improve survival rates for extremely preterm infants (born before 28 weeks).
- Neurodevelopmental disabilities, including cognitive dysfunction, are a significant concern in survivors.
- Understanding neocortical development is key to addressing these disabilities.
Purpose of the Study:
- To review recent findings on human neocortex development.
- To explore pathophysiological mechanisms of neurodevelopmental disabilities in extremely preterm infants.
- To identify potential targets for improved neonatal care.
Main Methods:
- Literature review of recent findings on neocortical development.
- Summary of human- and primate-specific developmental events.
- Discussion of causal mechanisms for neurodevelopmental disabilities.
Main Results:
- Neocortical neurogenesis and neuronal migration are active around the birth of extremely preterm infants.
- Subplate expansion and maturation, indicative of axonal wiring, are prominent during this period.
- These dynamic developmental processes are vulnerable to injury.
Conclusions:
- Brain injuries in extremely preterm infants can disrupt critical neocortical development (neurogenesis, migration, subplate maturation).
- Disruptions in these processes are presumed to underlie subsequent neurodevelopmental disabilities.
- Considering these mechanisms is vital for optimizing maternal and neonatal care to improve long-term outcomes.
Aim:
Recent advances in perinatal and neonatal medicine have resulted in marked improvements in the survival rates of extremely preterm infants (born before 28 gestational weeks) around the world, and Japan is among the countries with the highest reported survival rates of extremely preterm infants. However, it remains a major concern that many survivors develop neurodevelopmental disabilities, including cognitive dysfunctions and neurodevelopmental disorders later in life. In order to understand the pathophysiological mechanisms underlying the neurodevelopmental disabilities observed in the survivors of extremely preterm births, we reviewed recently reported findings about the development of the human neocortex.
Methods:
First, we have summarized the current knowledge about the development of the neocortex, including recently reported human- and/or primate-specific developmental events. Next, we discussed the possible causal mechanisms underlying the development of neurodevelopmental disabilities in extremely preterm infants.
Results:
Around the birth of extremely preterm infants, neurogenesis and succeeding neuronal migrations are ongoing in the neocortex of human brain. Expansion and maturation of the subplate, which is thought to reflect the axonal wiring in the neocortex, is also prominent at this time.
Conclusion:
Brain injuries that occur around the birth of extremely preterm infants are presumed to affect the dynamic developmental events in the neocortex, such as neurogenesis, neuronal migrations and maturation of the subplate, which could underlie the neurodevelopmental disabilities that often develop subsequently in extremely preterm infants. These possibilities should be borne in mind while considering maternal and neonatal care to further improve the long-term outcomes of extremely preterm infants.
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