Institution
University of Manchester
Scientific title
Identifying new treatments for intracerebral haemorrhage
Principal Investigator
Dr Paul Kasher
Year awarded
2019
Region
Grant value
£79,715.00
Research ID
SA PG 19\100026
Research area
Start date
Monday 4 November 2019
End date
Monday 3 May 2021
Status
Active

Background

An intracerebral haemorrhage (ICH) is a bleed within the brain and it’s a type of stroke. It accounts for around 10% of all strokes. It leads to brain damage, disability and often death – around one third of ICH patients die within one month. Apart from medication to reduce their blood pressure, there are currently no effective medicines that can be given to ICH patients to stop or reduce the damage an ICH causes to the brain.

It’s incredibly difficult to get access to human patients who are having an ICH soon after it started. This means we don’t currently know much about the early effects a bleed has on the brain, such as how brain cells react to bleeding. We need to know this to be able to develop treatments for patients that can stop or slow the changes in the brain and reduce the amount of damage an ICH causes.

One way to find out what happens within the brain during an ICH is to use animal models of the condition. In these models scientists cause an ICH and then observe the effects.  Dr Kasher’s previous research has shown that they can cause young zebrafish (also called larvae) to have an ICH. They also found that when they do this the larvae’s brain cells and molecules react in the same way as humans.

One advantage of using zebrafish larvae in this type of research is that they’re transparent. This means that, using very powerful microscopes, researchers can see the changes that happen in their living brains following a bleed.

Aims

This research will use a zebrafish model of ICH to identify drugs that could reduce the amount of brain injury an ICH causes, and which could go on to be tested in humans as a potential treatment for ICH.

Methods

The researchers will test 2000 drugs on zebrafish larvae which have recently had an ICH. Half of the drugs they're testing are already approved to treat other conditions in humans. They’ll use high powered microscopes to see what effect each of the drugs tested has. They’ll be looking to see whether the drugs have reduced the amount of brain injury the ICH causes in the zebrafish larvae.

When they’ve found some drugs that look like they reduce the amount of brain injury, the researchers will look back at the drugs to see which molecules they have been designed to affect.

They’ll then look at brain tissue and blood samples from human patients who have had an ICH to see which of these molecules are present at an abnormally high or low level, or are missing when they should be present. If the molecule is abnormal in the human samples, then the researchers will know that the drug identified from the testing in the zebrafish larvae may play an important role in affecting the way that ICH damages the brain in humans.

The researchers can then consider whether the drug should be tested in human patients in the future as a potential treatment to reduce the effects of ICH.

Impact

Many of the drugs that will be tested are known to be safe in humans. This means that, while they’ll still be a long way from being used to treat ICH every day, any drugs that appear to reduce the amount of brain damage could go on to clinical trials in human patients more quickly.

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