Cell age–specific vulnerability of neurons to anesthetic toxicity
Article first published online: 5 JUN 2013
© 2013 American Neurological Association
Annals of Neurology
Volume 73, Issue 6, pages 695–704, June 2013
How to Cite
Hofacer, R. D., Deng, M., Ward, C. G., Joseph, B., Hughes, E. A., Jiang, C., Danzer, S. C. and Loepke, A. W. (2013), Cell age–specific vulnerability of neurons to anesthetic toxicity. Ann Neurol., 73: 695–704. doi: 10.1002/ana.23892
- Issue published online: 18 JUL 2013
- Article first published online: 5 JUN 2013
- Accepted manuscript online: 22 MAR 2013 08:39PM EST
- Manuscript Accepted: 1 MAR 2013
- Manuscript Revised: 29 JAN 2013
- Manuscript Received: 20 DEC 2012
- NIH National Institute of Neurological Disorders and Stroke. Grant Numbers: 1R01-NS-065020, 1R01-NS-062806; S.C.D
Anesthetics have been linked to widespread neuronal cell death in neonatal animals. Epidemiological human studies have associated early childhood anesthesia with long-term neurobehavioral abnormalities, raising substantial concerns that anesthetics may cause similar cell death in young children. However, key aspects of the phenomenon remain unclear, such as why certain neurons die, whereas immediately adjacent neurons are seemingly unaffected, and why the immature brain is exquisitely vulnerable, whereas the mature brain seems resistant. Elucidating these questions is critical for assessing the phenomenon's applicability to humans, defining the susceptible age, predicting vulnerable neuronal populations, and devising mitigating strategies.
This study examines the effects of anesthetic exposure on late- and adult-generated neurons in newborn, juvenile, and adult mice, and characterizes vulnerable cells using birth-dating and immunohistochemical techniques.
We identify a critical period of cellular developmental during which neurons are susceptible to anesthesia-induced apoptosis. Importantly, we demonstrate that anesthetic neurotoxicity can extend into adulthood in brain regions with ongoing neurogenesis, such as dentate gyrus and olfactory bulb.
Our findings suggest that anesthetic vulnerability reflects the age of the neuron, not the age of the organism, and therefore may potentially not only be relevant to children but also to adults undergoing anesthesia. This observation further predicts differential heightened regional vulnerability to anesthetic neuroapoptosis to closely follow the distinct regional peaks in neurogenesis. This knowledge may help guide neurocognitive testing of specific neurological domains in humans following exposure to anesthesia, dependent on the individual's age during exposure. ANN NEUROL 2013;73:695–704