Melatonin Offers Hope for Brain-Damaged Children

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Axel Karl Gottfrid Nyman won the regional finals of the Researchers’ Grand Prix, where he presented his research "Nanomayonnaise for newborns with brain injury". Photo: Thor Nielsen, NTNU

MELATONIN: “The hormone melatonin can help children with brain damage. But it can’t yet be used effectively. My research aims to make treatment accessible,” says Axel Karl Gottfrid Nyman in the Department of Circulation and Medical Imaging at NTNU.

Nyman made it to the finals at the Researchers’ Grand Prix on 30 September this year. His field of research has the potential to impact a lot of people and their loved ones.

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Nyman wants to increase the chance for melatonin to work in treating newborns with brain damage. Photo: Julie Gloppe Solem, NTNU

Every two minutes, a child is born with brain injury. We don’t always know why, but the most common known cause is too little blood and oxygen reaching the brain. The consequences can be dramatic and lead to a life with cerebral palsy, impaired concentration, epilepsy or a permanent need for support and help.

Difficult treatment

Brain injury in newborns is difficult to treat. Some children can be treated by cooling the body, but this is a potentially risky treatment that cannot be used on preemies, and one that is not fully effective and can only be offered in settings able to provide cutting-edge intensive care. New treatment options are urgently needed.

The hormone melatonin is best known as the regulator of our body’s daily rhythm. When the retina of the eye stops receiving light in the evening, it sends signals to the brain’s pineal gland (epiphysis cerebri). This gland excretes melatonin, which in turn makes us feel tired and want to sleep.

Antioxidant

But in evolutionary history, melatonin played a completely different role. Long before animals with circadian rhythms walked the Earth, the atmosphere consisted primarily of nitrogen and carbon dioxide, and life was adapted to this. But then, about 2.4 billion years ago, the atmosphere’s oxygen content increased enormously.

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Newborns don’t start properly producing melatonin and other antioxidants until they are several months old. Babies are therefore particularly vulnerable to diseases that cause harmful oxygen in the body. Photo: Colourbox

This change resulted in a mass extinction of life on Earth. Oxygen is an extremely reactive substance that would be highly toxic without the defence that we’ve developed against it. The bacteria that managed to survive developed such a defence: melatonin.

Melatonin acts as an antioxidant – a substance that protects us against dangerous oxygen. Since melatonin is light sensitive and breaks down during the day, it later took on other functions – like signalling that it’s nighttime and time to sleep.

Babies have little melatonin

Many people know that newborn rhythms don’t always work for parents. That’s because newborns don’t properly start producing melatonin and other antioxidants until they are a few months old.

Babies are therefore particularly vulnerable to diseases that cause harmful oxygen in the body – like brain injury due to low oxygen levels and reduced blood flow.

Has to be dissolved

So why not give newborns melatonin now? One of the problems is that melatonin is only slightly water-soluble. To inject high doses into the bloodstream, which is believed to be important for best effect, it needs to be dissolved in solvents.

These solvents can have harmful effects on the brain and cancel out the beneficial effect of melatonin.

Giving the drug in tablet form is an alternative method. The problem with this method is that melatonin breaks down in the liver before it reaches the brain, so half or more of the melatonin may never reach its intended destination. This method is also much slower.

New nano method

“In my PhD project we’re testing a third method: encapsulating melatonin into fatty nanoparticles,” says Nyman.

Melatonin dissolves well in fat.

“By using a kind of nanomayonnaise consisting of tiny drops of melatonin-saturated fat in water, we can administer large doses into the blood in a short period of time, without using harmful solvents,” Nyman says.

A lot of testing ahead

Before this new treatment is ready for human use, it has to be tested on rats.

“I’m going to look at how much melatonin the brain absorbs with the new nanoparticles compared to melatonin in traditional solvents,” says Nyman.

Next, Nyman will attempt to treat newborn rats with brain damage and measure the effect compared with traditional solvents.

If the results are promising, other experimental groups will have the opportunity to repeat Nyman’s experiments before pharmaceutical companies further develop the particles and ultimately reach the children who need them.

Source : Gemini Research News from NTNU and SINTEF