Does Anesthesia alter Pediatric Brains?

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Most of us have heard the warning “Don’t drink too much alcohol, it will kill your brain cells,” but, does this warning now apply to anesthesia during neurodevelopment as well? There are many reports out there saying anesthesia may kill brain cells or alter the ability to learn. How much and what kind of evidence is out there? How should this evidence alter our practice of anesthesia?

How should this evidence alter our practice of anesthesia?

Broadly speaking, there are 3 types of reports on anesthesia administered during neurodevelopment. The first is retrospective clinical studies. Most of these studies examine a cohort that received anesthesia at a young age and measured cognitive ability later in life. While these studies suggest a potential link between exposure to anesthesia during development and impaired learning, the studies cannot say that the anesthesia caused learning impairment.

The more compelling evidence is found in the animal models. This brings us to the second type of reports – the structural data. Many of these reports compare animals exposed to anesthesia or not at an early stage of development and then examine the neurons structure, cell number, and neuron's organelles. They describe negative changes to the form of the brain cells, the neurons. Many of these studies examine a sub-region of the hippocampus, the brain’s location for learning and memory. They show negative changes to the mitochondria (the cell’s powerhouse, and a key indicator of whether a cell will commit programed cell death) as well as a decrease in the number of connections between neurons. This strongly suggests a possible decrease in neuronal function and a possible increase in cell death, although that was not directly measured in these studies.

The final type of report is the most compelling evidence that anesthesia delivered during key developmental time points alters brain function. Again, in animal models, but this time, with functional data. These reports compare the functionality of the hippocampus, not just alterations in structure. Some groups have measured a significant increase in pro-death markers, indicating an increase in programmed cell death in the hippocampus.

Other groups measured neuronal function. For years now, neuroscientist have measured learning and memory based on the hippocampus’ electrical output. One group measured the electrical output of the hippocampus in adult rats that were exposed to anesthesia at an early developmental time point. What they found, when compared to several different controls, was a change in the electrical output – a decrease in the electrical measurement used to determine if the hippocampus can learn. So what is this electrical measurement? It’s called long-term potentiation (LTP). And LTP, among other things, requires rapid influx of calcium through the NMDA receptor. Therefore it is entirely possible that early exposure to anesthesia has a long-term affect on NMDA receptor activation.

It is entirely possible that early exposure to anesthesia has a long-term affect on NMDA receptor activation.

If the animal studies are any indication of what happens in a human brain, then it is entirely possible that repeated exposure to anesthesia during periods of development could alter learning and memory. The results from the animal model taken together, reduced number of neuronal connections, increased programmed cell-death, as well as a decrease in NMDA activation would indeed alter an individual’s ability to learn. There is enough evidence in the animal models to warrant further investigation into how anesthesia alters the form and function of the neurons within the hippocampus if administered during development. To date, it appears that the effects observed in the animal model are dose-dependent. So, it is not simply a matter of whether or not a developing brain is exposed to anesthesia, but how many times it is exposed and for how long.

Jennifer Larimore, Ph.D.

Assistant Professor, Agnes Scott College