By: 13 August 2013

As paediatric specialists become increasingly aware that surgical anaesthesia may have lasting effects on the developing brains of young children, new research suggests the threat may also apply to adult brains.

Researchers from Cincinnati Children’s Hospital Medical Center report in Annals of Neurology that testing in laboratory mice shows anaesthesia’s neurotoxic effects depend on the age of the brain neurons – not the age of the animal undergoing anaesthesia, as once thought.

Although more research is needed to confirm the study’s relevance to humans, it suggests possible health implications for millions of children and adults who undergo surgical anaesthesia annually, according to Dr Andreas Loepke, a physician and researcher in the Department of Anesthesiology.

“We demonstrate that anaesthesia-induced cell death in neurons is not limited to the immature brain, as previously believed,” said Loepke. “Instead, vulnerability seems to target neurons of a certain age and maturational stage. This finding brings us a step closer to understanding the phenomenon’s underlying mechanism.”

New neurons are generated abundantly in most regions of the very young brain, explaining why previous research has focused on that developmental stage. In a mature brain, neuron formation slows considerably, but extends into later life in the dentate gyrus and the olfactory bulb.

The dentate gyrus, which helps control learning and memory, is the region Loepke and his research colleagues paid particular attention to in their study. Also collaborating were researchers from the University of Cincinnati College of Medicine and the Children’s Hospital of Fudan University, Shanghai, China.

Researchers exposed newborn, juvenile and young adult mice to a widely used anaesthetic called isoflurane in doses approximating those used in surgical practice. Newborn mice exhibited widespread neuronal loss in forebrain structures – confirming previous research – with no significant impact on the dentate gyrus. However, the effect in juvenile mice was reversed, with minimal neuronal impact in the forebrain regions and significant cell death in the dentate gyrus.

Research over the past 10 years has made it increasingly clear that commonly used anaesthetics increase brain cell death in developing animals, raising concerns from the Food and Drug Administration (FDA), clinicians, neuroscientists and the public. Several follow-up studies in children and adults who have undergone surgical anaesthesia show a link to learning and memory impairment.

Cautioning against immediate application of the current study’s findings to children and adults undergoing anaesthesia, Loepke said his research team is trying to learn enough about anaesthesia’s impact on brain chemistry to develop protective therapeutic strategies, in case they are needed. To this end, their next step is to identify specific molecular processes triggered by anaesthesia that lead to brain cell death.
Loepke said: “Physicians should carefully discuss with patients, parents and caretakers the risks and benefits of procedures requiring anaesthetics, as well as the known risks of not treating certain conditions.”