Gothenburg, Sweden. There is a link between repeated anaesthesia in children and memory impairment, though physical activity can help to form new cells that improve memory, reveals new research in the Journal of Cerebral Blood Flow & Metabolism.

Significantly improved surgical procedures are now available for children, and with the trend toward early intervention, paediatric anaesthetists have long suspected that children subjected to repeated anaesthesia over the course of just a few years may suffer from impaired memory and learning.

Klas Blomgren is a professor at the Queen Silvia Children’s Hospital and a researcher working out of the Sahlgrenska Academy at the University of Gothenburg, Sweden. His research team discovered, by chance, a link between stem cell loss and repeated anaesthesia when working on another study.

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In this research, the team investigated what happens to the brain’s stem cells when exposed to strong magnetic fields, for example during an MRI scan. The study was carried out using rats and mice, and showed that while the magnetic fields did not have any tangible effects on the animals, the repeated anaesthesia did.

”We found that repeated anaesthesia wiped out a large portion of the stem cells in the hippocampus, an area of the brain that is important for memory,” says Blomgren. ”The stem cells in the hippocampus can form new nerve and glial cells, and the formation of nerve cells is considered important for our memory function.”

Their results could also be linked to impaired memory in animals as they got older. The effect was evident only in young rats or mice that had been anaesthetised, not when adult animals were anaesthetised. This may be because stem cells are more sensitive in an immature brain, even though there are fewer of them as we get older.

”Despite extensive attempts, we have not been able to understand exactly what happens when the stem cells are wiped out,” says Blomgren. ”We couldn’t see any signs of increased cell death, but are speculating that the stem cells lose their ability to divide.”

Another treatment that wipes out the brain’s stem cells is radiotherapy, which is used with cancer patients. Blomgren and his research team have previously used animal studies to show that physical activity after radiotherapy can result in a greater number of new stem cells and partly replace those that have been lost.

”What’s more, the new nerve cells seem to work better in animals that exercise. Now that we know this, we can come up with treatments that prevent or reverse the loss of ostem cells after repeated anaesthesia,” says Blomgren, who believes that the findings will lead to greater awareness of the problems and inspire further research into the reasons for the loss of stem cells.

Citation Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents. Changlian Zhu , Jianfeng Gao , Niklas Karlsson , Qian Li , Yu Zhang , Zhiheng Huang , Hongfu Li , H Georg Kuhn and Klas Blomgren. Journal of Cerebral Blood Flow & Metabolism 2010; ePub ahead of print. doi:10.1038/jcbfm.2009.274

Abstract

Isoflurane and related anesthetics are widely used to anesthetize children, ranging from premature babies to adolescents. Concerns have been raised about the safety of these anesthetics in pediatric patients, particularly regarding possible negative effects on cognition. The purpose of this study was to investigate the effects of repeated isoflurane exposure of juvenile and mature animals on cognition and neurogenesis. Postnatal day 14 (P14) rats and mice, as well as adult (P60) rats, were anesthetized with isoflurane for 35|[thinsp]|mins daily for four successive days. Object recognition, place learning and reversal learning as well as cell death and cytogenesis were evaluated. Object recognition and reversal learning were significantly impaired in isoflurane-treated young rats and mice, whereas adult animals were unaffected, and these deficits became more pronounced as the animals grew older. The memory deficit was paralleled by a decrease in the hippocampal stem cell pool and persistently reduced neurogenesis, subsequently causing a reduction in the number of dentate gyrus granule cell neurons in isoflurane-treated rats. There were no signs of increased cell death of progenitors or neurons in the hippocampus. These findings show a previously unknown mechanism of neurotoxicity, causing cognitive deficits in a clearly age-dependent manner.

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