Studies by researchers at Wake Forest University School of Medicine have shown that blocking the NMDA receptor in immature rats leads to profound, rapid brain injury and disruption of auditory function as the animals mature.
The N-methyl-D-aspartate (NMDA) receptor is activated when a chemical in the brain called glutamate is released by brain cells. This allows calcium to enter into these cells, which can then influence a wide array of important functions. By blocking the receptor, calcium entry is prevented, leading to loss of many of these functions.
Some types of anesthetics used in humans to perform medical procedures act by blocking this receptor, raising the question of whether such anesthetics could produce similar side effects in children exposed to the drugs at a young age.
Whether this is a real clinical issue for children is yet unknown, since all of the School of Medicine's studies on the subject are based on rodent models.
"While research in animals does not always apply to humans, our work with rats supports clinical studies by other groups that suggest learning deficits may occur in young children who have been exposed to general anesthesia," said Christopher P. Turner, Ph.D., an assistant professor of Neurobiology and Anatomy. Turner summarized his latest findings this week at the annual Society for Neuroscience meeting in Chicago. The summary consisted of back-to-back presentations of five studies using a rodent model of brain injury that have either been published this year in various journals or are scheduled to appear in upcoming issues.
"Over the past decade, we've identified and defined the injuries taking place in young rodent brains, understood the molecular changes that are occurring because of those injuries, and now we understand how those injuries may influence the behavior of laboratory animals that have been exposed to drugs that block the NMDA receptor," Turner said.
Turner and other neuroscientists began considering the potential effects of anesthesia on children after making the connection in animal studies that drugs such as MK801, which act in a similar manner to some general anesthetics by blocking the NMDA receptor, can cause brain injury in immature rodents.
Using rats equivalent in age to children in their last trimester of development through to two years old, the researchers injected MK801, blocking the NMDA receptor in the brain. Within hours, they noticed evidence of injury in many brain regions. The blocking of the receptor, and subsequent inhibition of calcium influx into the cells, caused changes in a variety of proteins critical to normal brain cell function in the rats, particularly communication.