Anesthetics in young children potentially impact brain development.
Fresh Take:
A recent study conducted on mice sheds light on the potentially harmful impact of a common anesthetic, isoflurane, on the development of neurons in the baby brain. This research supports a growing body of evidence that has raised concerns about the use of general anesthetics in children, especially those under three years old.
In the United States alone, hundreds of thousands of kids are given general anesthesia each year. However, the FDA issued a warning in April 2017 after studies indicated prolonged or repeated usage of these drugs could adversely affect a child's brain development during critical periods.
The warning came on the heels of studies suggesting long-term cognitive difficulties in children following anesthesia, such as poor performance on language and cognitive tests, and an increased risk of learning disorders.
The Effect of General Anesthesia on the Developing Brain
While these earlier studies don't definitively prove a direct link, they raise questions about other factors that might be involved, such as parental stress or underlying medical conditions.
Beyond human studies, animal research, including a study on infant rhesus monkeys, has reached similar conclusions. The most recent study, led by Eunchai Kang and Dr. David Mintz of the Johns Hopkins School of Medicine, delved deeper into the mystery of cognitive changes in infants.
In their study, published in PLOS Biology, the team used a mouse model and isoflurane, a general anesthetic commonly used in children. They focused on the dentate gyrus, a part of the hippocampus vital for learning and the formation of new memories.
Discovering the Impact of Isoflurane on the Developing Brain
Isoflurane, first approved for use in the U.S. in 1979, is generally considered safe and effective. In this study, the researchers exposed 15-day-old mice to 4-hour doses of isoflurane, equivalent to the doses used in children, and recorded the development of their hippocampus.
The team found that isoflurane had a significant impact on the dentate gyrus granule cells, causing their dendrites, or branches, to almost double in length compared to the control group. Granule cells in the dentate gyrus are essential for memory formation and develop particularly late.
The researchers also observed a reduction in the number of mature dendritic spines, the structures that house synapses. To investigate the impact of these changes on learning and behavior, the team conducted object-place recognition tests and Y-maze tests. The mice given isoflurane performed significantly worse in both tests.
Finally, the researchers hypothesized that a protein called mTOR might be involved in the negative cognitive effects and developmental changes in the brain observed in this study. They found that when rapamycin, a compound that suppresses the immune system and inhibits the mTOR pathway, was given alongside the anesthetic, the negative cognitive effects and developmental changes were prevented.
The Future of General Anesthesia Research
This study strengthens earlier conclusions that prolonged exposure to general anesthetics during development may negatively impact the growing brain. With far-reaching implications, further research into the mechanisms behind these effects will undoubtedly follow.
Parents and medical professionals might want to consider the potential long-term effects of general anesthesia on children's cognitive development when planning surgical procedures for infants and young children.
Deepen Your Understanding: While the provided studies suggest that early exposure to general anesthesia may lead to long-term cognitive difficulties and functional connectivity changes, the specific role of the mTOR pathway and the dentate gyrus is yet to be directly examined in human-relevant models. Future research should explore these pathways and brain regions to better understand the molecular mechanisms behind the observed cognitive deficits.
- The study led by Eunchai Kang and Dr. David Mintz of the Johns Hopkins School of Medicine focused on the neurodevelopmental effects of the general anesthetic isoflurane, a drug commonly used in children.
- The researchers found that isoflurane caused significant changes in the dentate gyrus granule cells of 15-day-old mice, specifically lengthening their dendrites nearly double that of the control group.
- The reduction in the number of mature dendritic spines and the poor performance of the mice in object-place recognition tests and Y-maze tests suggest that isoflurane may negatively impact learning and behavior.
- To investigate the potential mechanisms behind these effects, the team hypothesized that a protein called mTOR might be involved and found that rapamycin, a compound that inhibits the mTOR pathway, prevented the negative cognitive effects and developmental changes.
- Given the potential long-term effects on children's cognitive development, medical professionals and parents may want to carefully consider the use of general anesthesia in infants and young children.
- Further research is needed to better understand the molecular mechanisms behind the observed cognitive deficits, including the specific role of the mTOR pathway and the dentate gyrus in human-relevant models, as outlined in the FDA's April 2017 warning about the use of general anesthetics in children.
