Islamabad - A study carried out in mice finds that a common general anaesthetic called isoflurane significantly interferes with the growth of neurons in the developing brain. These worrying findings back up a raft of earlier studies.

a team of researchers set out to understand what might be going on in the brain to produce these cognitive changes in infants. To this end, they used a mouse model and the general anaesthetic isoflurane.

The group was led by Eunchai Kang and Dr David Mintz, both of the Johns Hopkins School of Medicine in Baltimore, MD, and their findings are published this week in PLOS Biology.

Isoflurane was first approved for use in the U.S. in 1979. It is regularly used in children and is generally considered safe and effective.

The researchers were specifically interested in charting its impact on the dentate gyrus, a part of the hippocampus. This region of the brain is vital for learning and the formation of new memories. The hippocampus houses a large population of neurons that develop in the period shortly after birth.

In particular, the dentate gyrus granule cells were significantly affected by the anaesthetic; their dendrites, or branches, were almost twice the length of those in the untreated control mice.

The granule cells in the dentate gyrus are known to be important in memory formation but develop particularly late.

The team also saw a reduction in the number of mature dendritic spines, the structures that house synapses.

In the next phase of the study, the researchers investigated the effect of these changes on learning and behaviour. Using an object-place recognition test and a Y-maze test, the mice were put through their paces.

In the final arm of the study, the researchers gleaned some insight into how the anaesthetic might be producing these negative changes, and a protein known as mTOR appears to be involved.

mTOR acts as a hub, collating signals from a number of sources. It was chosen by the scientists as a potential target in this study because it has been linked with other neuro developmental disorders, such as autism spectrum disorders and schizophrenia.

Rapamycin, a compound that suppresses the immune system, also inhibits the mTOR pathway; they found that when rapamycin was given alongside the anaesthetic, the negative cognitive effects and developmental changes in the brain were prevented. This infers that mTOR may be involved in the molecular mechanisms behind the altered brain development.

The authors write:

“Taken together, our findings indicate that isoflurane causes a sustained increase in activity in the mTOR pathway that leads to dendrite growth acceleration and either synapse loss or reduced synapse formation in DGCs [dentate gyrus granule cells].”

The study firms up earlier conclusions that significant exposure to general anaesthetics during development negatively impacts the growing brain. Because of the wide-ranging implications of the study, more research will no doubt follow hot on its heels.

Meanwhile, A new study finds that lutein, a compound that gives egg yolk and some plants their colour, can reduce chronic inflammation in patients with coronary artery disease, the most common type of heart disease.

Coronary artery disease develops because a process called atherosclerosis builds up fatty deposits, or plaque, in the walls of the arteries that supply blood to the heart. This results in narrowing arteries that can partially or totally block the flow of blood.

Over time, as the plaque builds up and the arteries become narrower, the heart muscle does not get enough blood. This can cause angina, which is a condition felt as pain or discomfort in the chest and the most common symptom of coronary artery disease.

Coronary artery disease can also lead to heart failure, a condition wherein the heart cannot pump enough blood to meet the body’s needs. Other problems, such as irregular heartbeat, or arrhythmia, can also develop.

Advances in basic science have shown that atherosclerosis is not just a fat-depositing process; it also involves an ongoing inflammatory response that plays a key role in all stages of the disease. Study leader Lena Jonasson, who is a cardiology consultant and LiU professor in medical and health sciences, says, “We know that chronic inflammation is associated with a poorer prognosis.”

She explains that a significant number of patients who have had a heart attack continue to have persistent low-level inflammation in their bodies, even after effective treatments that involve drugs, revascularization, and lifestyle changes.

Prof. Jonasson and colleagues refer to previous studies that have suggested that what we eat can affect inflammation in our bodies.

They highlight a group of compounds called carotenoids, which are “antioxidants with potential anti-inflammatory properties.”

Carotenoids are a large family of fat-soluble pigments - that is, compounds that give color to other materials - that are naturally present in vegetables and some animal foods.

The family includes some well-known pigments such as beta-carotene and lycopene. Foods that are rich in lutein - the carotenoid at the center of the new study - include dark green leafy vegetables such as spinach, parsley, and kale. Lutein is also present in egg yolk.

Several studies have found that low levels of carotenoids are linked to higher levels of inflammation markers in the blood. Prof. Jonasson and colleagues wanted to investigate this further, to address the question of whether or not carotenoids themselves possess anti-inflammatory effects.

However, the results showed that lutein was the only carotenoid that showed an association with levels of IL-6: “the higher the level of lutein in the blood, the lower the level of IL-6.”

Prof. Jonasson comments, “The patients were receiving the best possible treatment for their disease according to clinical guidelines, but even so, many of them had a persistent inflammation. At the same time, the patients had lower levels of lutein.”

The team then explored what might be happening at the cell level to produce this effect. After studying immune cells isolated from the blood of patients with coronary artery disease, they found that treatment with lutein reduced the cells’ inflammation activity. The carotenoid reduced the cells’ production and release of inflammatory cytokines, which are signaling molecules that promote inflammation.