14 June 2018

New discovery about the brain’s water system may prove beneficial in stroke

Intracranial pressure Water is transported from the blood into the brain via an ion transporter, a new study on mice conducted at the University of Copenhagen reveals. If the mechanism can be targeted with medicine, it may prove relevant to all disorders involving increased intracranial pressure, including brain oedema in connection with stroke as well as hydrocephalus, also called ‘water in the head’.

The brain rests in a fluid, which among other things protects it from concussions. Scientists have known this for centuries. Every day around half a litre of water is transported from the blood to the brain through a thin tissue called plexus choroideus. But exactly how this is done has so far been quite a mystery.

In a new study published in Nature Communications researchers at the University of Copenhagen have proven for the first time on mice models that the transport is not controlled by osmosis, as many used to believe. Instead water is primarily transported to the brain via a so-called co-transporter, which moves a certain amount of water when ions are transported across the tissue plexus choroideus.

’It is brand new knowledge on a very important physiological process involving the by far most complex organ in the human body, namely the brain. If we are able to target this ion and water transporter with medicine, it would affect a number of disorders involving increased intracranial pressure, including brain haemorrhage, blood clots in the brain and hydrocephalus’, says Associate Professor at the Department of Neuroscience Nanna MacAulay.





Severe Consequences of Increased Pressure

The researchers have examined the tissue plexus choroideus in mice and tested whether water can be moved through the tissue even though the conditions required for osmotic water transport are missing. This turned out to be the case; a different process thus had to be responsible for the water transport.

They then did tests on live mice to see how fast brain fluid is produced when possible water transporters are inhibited. This revealed that the co-transporter in question is responsible for half of all fluid production for the brain cavity and is thus the main water transporter in this tissue.

‘Of course, it would be ground-breaking if we were able to use this mechanism as a target for medical treatment and turn down the inflow of water to the brain to reduce intracranial pressure. There are no effective medical treatments for a lot of disorders involving increased intracranial pressure. And at worst, the patient may suffer permanent damage and even die as a result of increased pressure. Therefore, this basic mechanism is an important find to us’, says Nanna MacAulay.

The researchers stress that the structure of the responsible proteins is the same in mice as in the human cell membrane in plexus chorideus. Therefore, they expect to find the same mechanisms in humans.

As a next step they will try to determine how the inflow of water to the brain can be affected and controlled using the newly discovered mechanism.

The study is based on tests in animals. Thus it has less statistical weight than case/control studies in humans and larger randomized trials in humans.

The study is funded by Lawyer Bent Thorberg’s Foundation, the Novo Nordisk Fonundation, the Independent Research Fund Denmark, the Vera and Carl Johan Michaelsen Scholarship, the Augustinus Foundation, Doctor Sofus Carl Emil Friis and Wife Olga Doris Friis’ Scholarship and the Carlsberg Foundation.

Scientific article:

‘Cotransporter-mediated water transport underlying cerebrospinal fluid formation’

Contact:

Associate Professor Nanna MacAulay

+45 35 32 75 66

macaulay@sund.ku.dk



Press Officer Mathias Traczyk

Tlf. 93 56 58 35

mathias.traczyk@sund.ku.dk