Researchers from Cincinnati Children's Hospital Medical Center report June 5 the Annals of Neurology
that testing in laboratory mice shows anesthesia's neurotoxic effects
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, according
to Andreas Loepke, MD, PhD, a physician and researcher in the
Department of Anesthesiology.
"We demonstrate that anesthesia-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 dentate gyrus and olfactory
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 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
Research over the past 10 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 said his
research team is trying to learn enough about anesthesia'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 anesthesia that lead to brain cell
"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."
Loepke is also collaborating with researchers from the Pediatric
Neuroimaging Research Consortium at Cincinnati Children's Hospital
Medical Center to examine anesthesia's impact on children's brain using
non-invasive magnetic resonance imaging (MRI) technology.
The current study was funded in part by grants from The Center
for Clinical and Translational Science and Training at the University of
Cincinnati, the Foundation for Anesthesia Education and Research and
the Masimo Foundation.