Anesthesia in baby rats stunts brain development - Mind Numbing

Science News, Feb 8, 2003 by K. Morgan

General anesthetic drugs that physicians commonly administer to children undergoing surgery, when given to baby rats, trigger brain cells to commit a cellular form of suicide that leads to lasting memory and learning deficits, neuroscientists have found. So far, there's no evidence of similar effects in children who have received anesthesia, researchers say.

As the brain develops, countless nerve cells branch out and meet up. Excess neurons are then pruned back through a programmed process of cell death, called apoptosis, which yields precise networks. In rats, connections form most abundantly in the first 3 weeks of life, whereas in people the most prolific connection making begins during the third trimester of pregnancy and continues for 2 to 3 years after birth.

Researchers have known for years that exposure to alcohol during the brain's growth spurt can ramp up cell death in rats and people. In children whose mothers drink heavily during late pregnancy, this cellular die-out can lead to hyperactivity and attention problems.

Like alcohol, anesthetic drugs stifle nerve cell activity. The anesthetics and alcohol act through the same mechanism. That led anesthesiologist Vesna Jevtovic-Todorovic of the University of Virginia in Charlottesville to ask whether early anesthesia might also share alcohol's influence on brain cells.

To find out, Jevtovic-Todorovic and her colleagues exposed 7-day-old rats to a triple cocktail of general anesthetics--midazolam, nitrous oxide, and isoflurane--a common combination in pediatric surgery. The treatment lasted 6 hours. Control rats received mock anesthesia treatments. The team killed some of the animals to study the pattern of brain-cell death and kept others alive for behavioral studies.

In the Feb. 1 Journal of Neuroscience, the scientists report that the anesthesia caused a substantial increase in cell death in many regions of the rats' brains including the hippocampus, a portion known for its role in learning and memory. Furthermore, 1-month-old rats that previously had been anesthetized scored poorly, compared with control rats, on tests of learning and memory. The rodents' mental deficiencies extended into adulthood, the team found.

"Rats that were given the anesthetic took longer to learn and tended to forget quickly, while control animals could go right back to a task," says Jevtovic-Todorovic. "Outwardly, they looked exactly the same."

Whether anesthesia's effects on young rats are relevant to people isn't known. Until it is, the results suggest"if surgery does not have to be performed early in life, it would be prudent to postpone it," says study coauthor John W. Olney, a neuropharmacologist at Washington University in St. Louis.

Neil L. Harrison, a neuroscientist at Cornell University in New York City calls the results "provocative" However, he warns against undue alarm. Doctors have administered anesthetics to babies "for many years without any apparent adverse effects," he says.