How heart disease affects brain development

Many children have congenital heart disease (CHD), which is one of the most common birth defects in the United States. These children not only have dysfunction in the heart, but also are prone to central nervous system dysfunction such as behavior, thinking and learning. Now, researchers have for the first time revealed how brain hypoxia-induced brain hypoxia can hinder neonatal brain development. This paves the way for the development of potential therapies that can be used before the baby is born.

How heart disease affects brain development

Caitlin Rollins, a child neurologist at Boston Children's Hospital, believes the results are very exciting and provide insight into the molecular and cellular mechanisms underlying this brain injury that will help develop drugs for pregnant women, thereby blocking this. Lesion process.

In patients with CHD, due to insufficient heart function, the transport efficiency of oxygen to the brain is reduced. Oxygen cannot meet the basic needs of the fetal brain, resulting in cerebral hypoxia. Cerebral hypoxia is the main cause of brain injury, so that fetal brain abnormalities can be found by magnetic resonance imaging (MRI) at 3 months of gestational age, and abnormal cardiac findings can be found by routine ultrasound examination. But until recently, scientists still do not understand the underlying cytological basis of fetal brain development disorders.


Scientists at the National Children's Health System in Washington have kept piglets in a hypoxic state, and found that animal brain lesions are consistent with the pathological type of brain damage in human CHD. Two days after the birth of the piglet, the researchers injected the animal with a fluorescent cell marker that labeled the cells in the subventricular zone. The subventricular zone of mammalian neonates is the largest collection of neural stem cells from which stem cells migrate to multiple brain regions and differentiate into multiple types of neural tissue cells.

The researchers then gave the animals a breath of 10.5% oxygen, which is about half the oxygen concentration in the air (21%). Fourteen days after birth, the researchers analyzed the brain tissue of these animals. The control animals continuously breathed normal air, and the other operations were the same. In addition, the researchers conducted a comparative study of brain tissue from four children who died of CHD and five humans who died of other causes within 0 to 36 days after birth.

The results showed that neurons produced by the neural stem cells in the subventricular zone of the pig migrated to the prefrontal cortex 1 week after birth. The research paper was recently published in the journal Science-Transformation Medicine. In the human brain, the prefrontal cortex is primarily responsible for advanced thinking. These cells mainly differentiate into interneurons, which generally inhibit neurons and inhibit excitatory neurons. Excitement and inhibition of balance are important prerequisites for the normal realization of advanced brain functions such as judgment, comprehensive facts and problem solving.

In piglets that continue to be under hypoxia, the neural stem cells in the subventricular zone are severely damaged, and the number of neurons and interneurons in the prefrontal cortex is significantly reduced. Their brain volume and weight were significantly smaller than those of the control group, and the surface cortex of the cerebral cortex was significantly less than that of the control group. In human children, compared with children who died from other causes, the brain of children who died of CHD also showed a decrease in the number of neural stem cells in the subventricular zone, and a significant decrease in brain weight and cerebral cortex gray matter.

Scientists say that, in fact, the neonatal brain is still developing during the weeks after birth, which provides a critical opportunity to treat the disease. Richard Jonas, a cardiac surgery specialist involved in the study, said that neurons can continue to develop after birth, providing a cytological basis for early treatment of brain damage in children with CHD.

Although this finding does not immediately translate into clinical applications, it also excites pediatricians and cardiac surgeons. According to Steven Miller, a pediatric neurologist at the Toronto Pediatric Hospital in Canada, this is the first step toward clinical application. In the future, it will try to stimulate the subventricular zone to produce more newborn neurons to supplement the number of neurons in children with CHD.

The study also has shortcomings. This pig model does not reflect the true situation of human heart disease patients, and does not reflect the hypoxia process in human uterus. It only represents the hypoxia after birth. Arnold Kriegstein, a neuroscientist at the University of California, San Francisco, also believes that only intermediate inhibitory neuronal reduction is not sufficient to explain brain volume and cortical fold reduction. "Intermediate inhibitory neurons may be part of the story, not the whole story," he said.