A substance related to a party drug could limit damage caused by stroke
Was able to limit the expansion of brain damage after stroke by up to 50%.
In animal trials, an international research group, headed by Professor Petrine Wellendorph from the University of Copenhagen, was able to limit the expansion of brain damage after stroke by up to 50%.
A laboratory-produced variant of a neurotransmitter found in the brains of humans and other mammals proved to have unexpected effects.
In time, these findings may lead to novel drugs to help people affected by stroke caused by a blood clot in the brain.
The discovery was made by an international research group headed by Professor Petrine Wellendorph, from the Department of Drug Design and Pharmacology, University of Copenhagen (UCPH).
Researchers from the Netherlands, the USA and New Zealand also participated in the study, which was recently published in the scientific journal PNAS.
Professor Wellendorph has been researching the GHB neuromodulator for several years. She received funding from the Lundbeck Foundation for her work in the form of a Fellowship worth DKK 10 million in 2013 and a further research grant for the same amount in 2019.
‘As a neuromodulator, GHB is involved in a number of brain mechanisms. My ambition – more specifically – is to understand the role GHB plays in our brains,’ says Professor Wellendorph.
Partydrug
If you take a powerful dose of synthetically produced GHB – or “fantasy” as the so-called party drug is named – you will experience a “rush” or “high”. You will lose your inhibitions and feel free and relaxed.
However, experimenting with the drug is not without its dangers! The dose required for a rush is not far removed from a dose that, in the worst case, can end fatally. And if you do manage to survive your acquaintance with this illegal drug, which fortunately most people do, unpleasant withdrawal symptoms may be in store.
To understand the role that GHB plays in the brain under normal, non-party-going circumstances, it is necessary to map the binding site; in other words, the protein to which GHB primarily binds in a mammalian brain. Once we understand this protein, we can begin to decipher the comings and goings of GHB.
It is this key binding protein that Professor Wellendorph and her colleagues have now succeeded in identifying – and their success is due to a laboratory-produced variant of fantasy. This variant – which has no narcotic effect – was made by chemists at UCPH, who named it HOCPCA.
With the help of HOCPCA, Professor Wellendorph and her colleagues were able to map the GHB binding site in a mammalian brain by analysing the brain tissue of rats.
Stroke in the lab
In the article in PNAS, the researchers also describe an experiment they performed on mice.
The aim of the experiment was to see whether HOCPCA – the laboratory-produced variant of fantasy – could be used to treat the damage caused by stroke.
To investigate this, Professor Wellendorph and her colleagues worked with two groups of laboratory mice, and all subjects were given an injection of a drug to provoke stroke.
One of the groups, Cohort 1, was then injected with HOCPCA. Cohort 2 was not given the substance.
Cohort 1 received injections of HOCPCA at various intervals. Some mice were given an injection three hours after the stroke, others after six hours, and the remainder after 12 hours.
Once all the results had been collated, the researchers could see that HOCPCA had had a significantly limiting effect on the damage. Professor Wellendorph explains:
‘In a stroke, the supply of oxygen and nutrients to an area of the brain via the bloodstream is temporarily constricted – or cut off altogether. This causes damage, so it’s always important to treat the patient as quickly as possible to restore the blood supply. Our experiment showed 40–50% less damage in the group of mice given HOCPCA compared with the animals that did not receive the drug. And this protective effect was also visible when HOCPCA was given 12 hours after we had provoked the stroke.’
They established this by measuring the size of the area in the brain to which the damage from the stroke had spread in the mice in both cohorts – as well as the depth at which the aftereffects could be detected in the brain tissue.
The researchers do not know how HOCPCA caused this protective effect in the mice in Cohort 1. However, the hypothesis is that it has something to do with calcium.
Professor Wellendorph explains that when someone has a stroke, there is a dramatic rise in the level of calcium in the brain, and the researchers therefore presume that HOCPCA may in some way scale down the calcium levels after a stroke.
In time, it may be possible to incorporate HOCPCA into a drug to limit the aftereffects of strokes in humans.
‘Together with UCPH, we’ve patented the drug, and we’re now applying for funds to conduct further studies. Even if it works in animal trials, we can’t simply assume that it will have a similar effect in humans. We’ll see how far we can get,’ says Professor Wellendorph.