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Published on: May 26, 2023
Impact of Cardiopulmonary Bypass on Neurogenesis and Cortical Maturation
Zaenab Dhari1, Camille Leonetti1, Stephen Lin2
1Children's National Heart Institute, Center for Neuroscience Research, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC.
Insights
Cardiopulmonary bypass (CPB) impairs neurogenesis and cortical maturation in piglets, leading to developmental delays similar to those seen in children with congenital heart disease. Refinements in CPB are needed to mitigate these neurological effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatric Cardiology
Background:
- Congenital heart disease (CHD) is associated with neurodevelopmental delays and frontal lobe cortical dysmaturation in children.
- The subventricular zone (SVZ) is a critical site for neural stem and progenitor cells in the postnatal brain.
Purpose of the Study:
- To investigate the impact of cardiopulmonary bypass (CPB) on neurogenesis and cortical maturation.
- To examine the effects of CPB on the subventricular zone (SVZ) and frontal lobe development in a porcine model.
Main Methods:
- Piglets underwent mild or severe CPB, or no surgery (control).
- SVZ and frontal lobe tissues were analyzed using immunohistochemistry.
- Magnetic Resonance Imaging (MRI) assessed frontal lobe cortical development post-CPB.
Main Results:
- CPB significantly reduced SVZ neurogenic activity and neuronal migration up to 4 weeks post-procedure.
- MRI revealed decreased gyrification index and cortical volume, with increased fractional anisotropy after severe CPB.
- CPB induced changes in inhibitory neuron densities, suggesting an excitatory-inhibitory imbalance in the frontal cortex.
Conclusions:
- CPB adversely affects postnatal neurogenesis and cortical maturation, contributing to neurological impairments in CHD.
- Further improvements in CPB technology and surgical techniques are crucial to address long-term frontal cortical dysmaturation in pediatric CHD patients.
Objective:
Neurodevelopmental delays and frontal lobe cortical dysmaturation are widespread among children with congenital heart disease (CHD). The subventricular zone (SVZ) is the largest pool of neural stem/progenitor cells in the postnatal brain. Our aim is to determine the effects of cardiopulmonary bypass (CPB) on neurogenesis and cortical maturation in piglets whose SVZ development is similar to human infants.
Methods:
Three-week-old piglets (n = 29) were randomly assigned to control (no surgery), mild-CPB (34°C full flow for 60 minutes) and severe-CPB groups (25°C circulatory-arrest for 60 minutes). The SVZ and frontal lobe were analyzed with immunohistochemistry 3 days and 4 weeks postoperatively. MRI of the frontal lobe was used to assess cortical development.
Results:
SVZ neurogenic activity was reduced up to 4 weeks after both mild and severe CPB-induced insults. CPB also induced decreased migration of young neurons to the frontal lobe, demonstrating that CPB impairs postnatal neurogenesis. MRI 4 weeks after CPB displayed a decrease in gyrification index and cortical volume of the frontal lobe. Cortical fractional anisotropy was increased after severe CPB injury, indicating a prolonged deleterious impact of CPB on cortical maturation. Both CPB-induced insults displayed a significant change in densities of three major inhibitory neurons, suggesting excitatory-inhibitory imbalance in the frontal cortex. In addition, different CPB insults altered different subpopulations of inhibitory neurons.
Interpretation:
Our results provide novel insights into cellular mechanisms contributing to CHD-induced neurological impairments. Further refinement of CPB hardware and techniques is necessary to improve long-term frontal cortical dysmaturation observed in children with CHD. ANN NEUROL 2021;90:913-926.
