Researchers give insight into how brain awakens from anesthesia

WASHINGTON: The brain’s process of waking up from anaesthesia is aided by the same cells that protect the central nervous system from injury, according to a Mayo Clinic study that was published in Nature Neuroscience.

New approaches to treating complications following anaesthesia may be made possible by this research.

More than one-third of patients may have delirium, a side effect consisting of excessive sleepiness or hyperactivity, after emerging from anaesthesia. The brain’s microglia, which are unique immune cells, have been shown by Mayo researchers to protect neurons from the side effects of anaesthesia in order to trigger brain awakening.

“This is the first time we’ve seen microglia enhance and boost neuronal activity by physically engaging the brain circuits,” says Mayo Clinic neuroscientist Long-Jun Wu, senior author of the study.

The researchers observed microglia wedging between neurons and inhibitory synapses, suppressing neural activity under anaesthesia. The microglia appear to be trying to shield the neurons to counteract sedation.

The brain consists of a network of neurons that fire and spur activity throughout the body. Neurons are connected by synapses that receive and transmit signals enabling one to move, think, feel and communicate. In this environment, microglia help keep the brain healthy, stable and functioning. Although microglia were discovered more than 100 years ago, it wasn’t until the last 20 years that they became a serious research focus.

In the beginning, scientists only had fixed slides of microglia to examine, which offered still snapshots of these cells. Initially, it was thought that when neurons were not active and the brain was quiet, microglia were less active. Then technology made it possible to observe and study microglia in greater detail, including how they move.

“Microglia are unique brain cells because they have very dynamic processes. They move and dance around as they survey the brain. We now have powerful images that show their activity and movement,” said Dr. Wu.

Microglia (green) move and “dance” around actively monitoring the brain and interacting with a neuron (red).

For several years, Dr. Wu and his team have been leading research into how microglia and neurons communicate in healthy and unhealthy brains. For example, they have shown that microglia can dampen neuronal hyperactivity during seizures from epilepsy.

In 2019, researchers discovered that microglia can sense when the brain and its activity is being suppressed, for example, by anaesthesia. They found that microglia become more active and vigilant when this occurs.

“We now can see microglia increase their surveillance and patrol the brain’s neural activity like a police officer at night responding to suspicious activity when all else is quiet,” Dr Wu said.

Patients experiencing delirium or agitation when coming out of anesthesia can also feel hyperactive or experience extreme sluggishness. The researchers believe hyperactivity may result from the microglia intervening too much between the neuron and inhibitory synapses.

“If we can explore the role of microglia in various physiological states, such as sleep, we could apply this knowledge to improve patient care in clinical settings,” said Koichiro Haruwaka, Ph.D., lead author of the study and a Mayo Clinic senior research fellow.