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.
"It's not just that cells are dying," Turner said, "but we have now identified other pathologies that follow from blocking the NMDA receptor. For example, we have found that blocking the receptor results in the turning off of the brain's ability to regenerate new cells, which means that the brain cannot compensate for the cells that die.
"Imagine all of this going on during the time the brain is still developing," Turner added. "With all of these changes, it's not surprising that certain brain functions are diminished as animals get older. For example, immature animals exposed to MK801 are later unable to respond to auditory cues in a way that would be considered normal. A lot of learning in all animals depends on being able to efficiently process auditory information."
These findings, Turner said, could also have implications for research on schizophrenia. Many of the molecular, cellular and behavioral changes seen in this disorder NMDA receptor blockade, changes in proteins important for cell-to-cell communication, auditory deficits, and developmental brain injury are key features of the animal model used by the Turner lab.
"For a long time, res
|Contact: Jessica Guenzel|
Wake Forest University Baptist Medical Center