By: 15 July 2016
Compound shown to reduce brain damage caused by anaesthesia in early study

An experimental drug prevented learning deficits in young mice exposed repeatedly to anaesthesia, according to a study led by researchers from NYU Langone Medical Center and published in June in Science Translational Medicine.

The study results may have implications for children who must have several surgeries, and so are exposed repeatedly to general anaesthesia. Past studies have linked such exposure to a higher incidence of learning disabilities, attention deficits and hyperactivity.

Specifically, the research team found that the experimental drug CX546, part of the AMPAkine class in clinical trials for several neurological conditions, counters for the dampening effect of anaesthesia on nerve signalling. The treatment bolstered nerve cell activity as well as learning ability in mice recovering from repeated exposure to general anaesthesia.

“Each year, in the United States alone, more than a million children under age four undergo surgical procedures that require anaesthesia, and the numbers are growing,” says the study’s senior investigator Guang Yang, PhD, assistant professor of anesthesiology at NYU Langone. “There are currently no effective treatments to combat potential toxicity linked to repeated anaesthesia, and we would like to change that.”

Yang’s group took advantage of genetically engineered young mice that have protein markers which glow in response to changes in nerve function. Researchers then used advanced microscopy to visualize activity in their brains, comparing nerve signaling activity in those exposed to anaesthesia to those who were not.

The research team found that anaesthesia exposure resulted in a prolonged reduction of signal transmission among nerve cells following anaesthesia. They also observed that CX546 treatment enhances this transmission, along with learning and memory in mice exposed to anaesthesia.

The team studied the anaesthetic ketamine, which blocks NMDA (N-methyl-D-aspartate) receptor proteins that enable charged particles like calcium to flow into nerve cells, like electric switches that trigger and shape messages. In contrast, CX546 increases nerve cell activity and calcium influx into nerve cells by enhancing the activity of proteins called AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors.

“We were able to counter anaesthesia-induced deficits in the formation of connections between nerve cells and related learning problems,” says Yang. “This work is an important proof-of-principle study, and opens the door to a new direction for preventing long-term neurocognitive deficits.”

Reference: Lianyan Huang, Joseph Cichon, Ipe Ninan and Guang Yang. Post-anesthesia AMPA receptor potentiation prevents anesthesia-induced learning and synaptic deficits. Science Translational Medicine, June 2016 DOI: 10.1126/scitranslmed.aaf7151

Source: NYU Langone Medical Center / New York University School of Medicine