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Spectrum: Autism Research News

Fast-acting anesthetic sharpens images of rodent brains

by  /  11 May 2016
Sleepy solution: Mice treated with the anesthetic isoflurane show less blood flow in the brain over time (blue, top) than do those given the drug etomidate (bottom).
THIS ARTICLE IS MORE THAN FIVE YEARS OLD

This article is more than five years old. Autism research — and science in general — is constantly evolving, so older articles may contain information or theories that have been reevaluated since their original publication date.

A chemical commonly used in emergency rooms can anesthetize mice and rats for brain scans without distorting the images, according to a new study1.

Researchers routinely use functional magnetic resonance imaging (fMRI) to probe brain function in people as they rest or perform a task. The technique measures blood flow in the brain as a proxy for neural activity. To scan a rodent brain, however, a researcher must use an anesthetic to sedate the animal in order to stave off stress and squirminess.

Two commonly used anesthetics for rodent scans, isoflurane vapor and medetomidine, fail to sedate some mouse strains and may dilate blood vessels in the brains of others, weakening the surges in blood flow that mark active brain regions. As a result, the scans less reliably reflect brain activity.

In the new study, published in April in Scientific Reports, researchers compared these two compounds to etomidate, an intravenous anesthetic often used during emergency procedures in people. They tested each drug in one strain of rats and two strains of mice that are widely used as control animals. They also studied the drugs’ effects in a mouse model of autism called BTBR.

The researchers placed each animal in a custom-built cradle that rolls into a rodent-sized MRI machine. They primed the brain with drugs that perturb blood flow and monitored its response under each type of anesthesia.

Go with the flow:

In rats, the brain responded swiftly under all three types of anesthesia. But in mice, the two traditional anesthetics had drawbacks. Isoflurane produced a sluggish response, and medetomidine did not sedate mice in two of the strains, including the autism mice.

By contrast, etomidate sedated all of the rodent strains while also allowing the brain to regulate blood flow to activated areas. The etomidate-treated rodents recovered from their sedation within an hour. The results suggest that the emergency room drug is well suited for rodent scans.

The researchers went on to test etomidate in five other mouse models of autism, including those with mutations in an autism-linked gene — TSC2, CNTNAP2, SHANK3 or NLGN3 — as well as mice exposed to the chemical valproic acid, which triggers autism-like features. The anesthetic maintains the coupling between blood flow and brain activity in all of the rodent strains.

The findings suggest that etomidate improves the quality of brain scans from rodents and would allow researchers to compare brain function across different mouse models of autism.


References:
  1. Petrinovic M.M. et al. Sci. Rep. 6, 24523 (2016) PubMed
TAGS:   autism, fMRI, GABA, mouse models