
AsianScientist (Jun. 10, 2013) – As pediatric specialists become increasingly aware that surgical anesthesia may have lasting effects on the developing brains of young children, new research suggests the threat may also apply to adult brains.
A study published in the Annals of Neurology shows anesthesia’s neurotoxic effects in laboratory mice depend on the age of brain neurons – not the age of the animal undergoing anesthesia, as once thought.
Although more research is needed to confirm the study’s relevance to humans, the study suggests possible health implications for millions of children and adults who undergo surgical anesthesia annually, say the study authors from the Cincinnati Children’s Hospital Medical Center in the US and the Children’s Hospital of Fudan University in Shanghai, China.
“We demonstrate that anesthesia-induced cell death in neurons is not limited to the immature brain, as previously believed,” said Andreas Loepke, MD, PhD, a physician and researcher in the CCHMC Department of Anesthesiology. “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 dentate gyrus and olfactory bulb.
The dentate gyrus, which helps control learning and memory, is the region the researchers paid particular attention to in their study.
Researchers exposed newborn, juvenile, and young adult mice to a widely used anesthetic 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.
The team then performed extensive studies to discover that age and maturational stage of the affected neurons were the defining characteristics for vulnerability to anesthesia-induced neuronal cell death. The researchers observed similar results in young adult mice as well.
Research over the past ten years has made it increasingly clear that commonly used anesthetics increase brain cell death in developing animals, raising concerns from the Food and Drug Administration, clinicians, neuroscientists and the public. As well, several follow-up studies in children and adults who have undergone surgical anesthesia show a link to learning and memory impairment.
Cautioning against immediate application of the current study’s findings to children and adults undergoing anesthesia, Loepke now aims to identify specific molecular processes triggered by anesthesia that lead to brain cell death.
“Surgery is often vital to save lives or maintain quality of life and usually cannot be performed without general anesthesia,” Loepke said. “Physicians should carefully discuss with patients, parents and caretakers the risks and benefits of procedures requiring anesthetics, as well as the known risks of not treating certain conditions.”
The article can be found at: Hofacer RD et al. (2013) Cell age–specific vulnerability of neurons to anesthetic toxicity.
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Source: CCHMC; Photo: JL Johnson | AviationGeek.net/Flickr/CC.
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