Discovery may provide noninvasive approach to assessing toxic effects of anesthetic agents in children

Could looking at the eyes provide a new way of studying how anesthesia affects the developing brain? The retinas of immature mice exposed to one widely used general anesthetic show evidence of "programmed cell death," or apoptosis, reports a study in Anesthesia & Analgesia.

That discovery might provide a "window of opportunity" to develop a much-needed noninvasive approach to assessing the potential toxic effects of anesthetic agents on the brain in infants and children, according to the report by Dr. Richard J. Levy of Children's National Medical Center, Washington, D.C., and colleagues.

Retinal Apoptosis May Reflect Neurotoxic Effects of Anesthesia
The researchers performed a series of experiments to determine whether isoflurane induces apoptosis in the developing retina—a lining of light-sensitive tissue inside the eye that transmits visual information to the brain. Apoptosis is a "widespread and natural phenomenon" in the development of the central nervous system. This process might make the developing brain more vulnerable to the potential neurotoxic effects of anesthetic agents.

In the study, one-week-old mice were studied after brief exposure to the inhalant anesthetic isoflurane. Indicators of apoptosis in retinal cells were compared for isoflurane-exposed mouse pups versus animals exposed to air only.

The results showed increases in several different markers of apoptosis in the retinas of isoflurane-exposed mice. The patterns of apoptosis marker expression provided clues as to the pathways causing programmed cell death, including variations between different layers of the retina.

Some types of cells were strongly affected while others were relatively spared—differences that might be related to the timing of normal apoptosis. For example, Dr. Levy and colleagues note that light-sensitive photoreceptor cells within the retina showed no signs of anesthesia-induced apoptosis. This finding that "may indicate some level of protection" and may provide clues to developing new treatment approaches.

Why study the effects of anesthesia on retinal cells in mice? Common anesthetics induce widespread apoptosis of neurons (nerve cells) in the developing brain of mammals. In human infants and young children, exposure to anesthesia for unavoidable surgical procedures has been linked to the development of cognitive (intellectual) and behavioral disorders.

But so far, there's no evidence to confirm—or refute—that anesthetics cause neurotoxic effects in children. The International Anesthesia Research Society (IARS), in partnership with the US Food and Drug Administration, has launched a research initiative called SmartTots to address the critical public health issues associated with the safe use of anesthesia and sedatives in young children.

"The retina is unique in that it is the only portion of the central nervous system that can be directly visualized noninvasively," Dr. Levy and coauthors write. Methods evaluating the retina might, for the first time, provide a directly observable approach to assessing the effects of anesthetic agents on neural cells. One dye used in the study bound to cells undergoing apoptosis, providing a potential opportunity to visualize the process of programmed cell death in the developing retina

The researchers note that many important issues remain to be clarified by further research—especially the correspondence between anesthetic damage to the brain in mouse pups versus human children. Another key issue is whether the retinal cell apoptosis truly reflects anesthesia-induced damage occurring in the brain. "Ultimately," Dr. Levy and colleagues conclude, "we may be able to develop a noninvasive imaging modality to determine whether anesthesia-induced neuronal apoptosis occurs in infants and children."

Source: Wolters Kluwer


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