Hypoxia is a key factor in brain damage in congenital heart disease

Most children with complex congenital heart disease have neurological and functional abnormalities such as brain developmental disorders, delayed brain maturation, and even brain damage. Congenital heart disease is the most common birth defect. This child is not only dysfunctional in the heart, but also prone to central nervous system dysfunction such as behavior, thinking and learning. In the past, the survival rate of children with severe congenital heart disease was relatively low, and the problem of nerve damage in congenital heart disease was relatively unclear. With the improvement of treatments and treatment techniques for congenital heart disease, the survival rate of children with congenital heart disease is significantly improved, and the problem of central nervous system damage in congenital heart disease is becoming more and more prominent. Once the nervous system damage is caused, it is irreversible, so this problem is increasingly taken seriously by neonatology.

Hypoxia is a key factor in brain damage in congenital heart disease

The cellular basis of brain damage caused by congenital heart disease has not been very clear. A recent study from the University of Washington found that the number and function of neural stem cells caused by hypoxia in brain tissue may be caused by congenital heart disease. The key cause of injury, this discovery provides an important idea for the prevention and treatment of the disease. Caitlin Rollins, a child neurologist at Boston Children's Hospital, believes the results are very exciting and provides insight into the molecular and cellular mechanisms underlying this brain injury. She said that future use of drugs for pregnant women may block the process.



Congenital heart disease, due to lack of heart function, causes the efficiency of oxygen transport to the brain to decline, oxygen can not meet the basic needs of the fetal brain will cause hypoxia in the brain. Cerebral hypoxia is the basic cause of brain injury, so that the fetal dysplasia can be found by MRI in the gestational age of 3 months. The abnormality of the heart can be found by conventional ultrasound examination in the fetus of the third gestational age. But until recently, scientists still do not understand the intrinsic cytological basis of fetal brain development disorders.

The National Children's Health System Science in Washington, through continuous hypoxia in newborn pigs, found that the pathology of the animal's brain was consistent with the pathological type of brain damage after congenital heart disease in humans. Two days after the birth of the swine fever, the animal is injected with a fluorescent cell marker that marks 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 and differentiate into multiple types of neural tissue cells.

On the third day of birth, the researchers gave the animals a breath of 10.5% oxygen, which is half the oxygen concentration in the air (21%). When the animals breathe hypoxic gas for 11 consecutive days until 14 days after birth, the animal brain tissues were sacrificed and taken out, and the control animals continuously breathed normal air, and the other operations were the same. Researchers 0-36 days after birth, four died of congenital heart disease and five died of other causes of human corpses of children with brain tissue were compared. The research paper was published in the journal Science Translational Medicine.

At 1 week after birth, neurons produced by the neural stem cells in the subventricular zone of the pig migrate to the frontal cerebral cortex, which is responsible for advanced thinking in the forehead. These cells mainly differentiate into interneurons, which generally inhibit neurons and inhibit the electrical activity of excitatory neurons. Excitement and inhibition are important prerequisites for the normal realization of advanced brain functions such as judgment, fact synthesis and problem solving.

After hypoxic treatment of piglets, the neural stem cells in the subventricular zone were severely damaged, and the number of neurons and interneurons in the forebrain cortex was significantly reduced. The brain volume and weight of the hypoxic group were significantly lower than those of the control group, and the surface cortex of the cerebral cortex was significantly less than that of the control group. In contrast to children with other causes of death, the brains of human children who died of congenital heart disease 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.

The human neonatal brain is still developing during the weeks after birth, providing a critical opportunity to treat the disease. One of the authors, heart surgery specialist Richard Jonas said that neurons can continue to regenerate after birth, providing a cytological basis for early treatment of brain damage in children with congenital heart disease. Although this finding does not immediately translate into clinical applications, this finding is enough to excite pediatricians and cardiac surgeons. Steven Miller, a pediatric neurologist at the Toronto Pediatric Hospital, believes the study is very powerful and is the first step toward clinical application. In the future, it can try to stimulate the subventricular zone to produce more newborn neurons to supplement the number of neurons in children with congenital heart disease. Insufficient.

There are also deficiencies in the research. This pig model does not reflect the true situation of human heart disease patients. It does not reflect the hypoxia process in human uterus, and 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 entire story.