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The inflamed brain: why my research matters

Hannah Buggey

Hannah Buggey

In her shortlisted article for the Max Perutz Science Writing Award 2012, Hannah Buggey from the University of Manchester takes us through her research combating inflammation in the brain after a stroke. 

Picture yourself in the shower. Now imagine that familiar feeling when the water starts to build up around your feet, and you’re racing to finish washing out shampoo before water spills over the edge of the shower tray. This clogged up drain is similar to what happens during a stroke.

In your plumbing, a hairball sticks together with bits of soap and becomes lodged in the U-bend. In stroke, a clot often forms from a build-up of fatty plaques in our blood vessels — the ones we’re always being told can be avoided by eating cholesterol-lowering margarine. This clot can break away and travel through your blood into your brain where the vessels have lots of twists and ‘U-bends’.

When a clot gets stuck here, the areas of the brain the blood is feeding are cut off from their supply of oxygen and nutrients. In the same way that you need to act fast to stop the shower water spilling over the edge, you need to act fast after a stroke. Brain cells can’t cope without oxygen, and during a stroke two million of them die every minute.

I bet you know at least one person who’s had a stroke. That’s because it’s a huge problem: in the UK someone has a stroke every five minutes. Despite this, there’s still only one medicine available. When your shower gets clogged, you pour down drain-unblocker and it breaks up the hairball. This is essentially how the stroke drug tPA works. It gets infused into your blood and travels to the blockage. Here, it dissolves the clot, restoring blood flow to the brain.

So why does my research matter? The trouble with tPA all comes back to acting fast. Doctors can only give you tPA if you get to the hospital within 4.5 hours after having a stroke.

Shockingly, only 20 per cent of patients make it in time for this window. Just like the shower flooding if you act too slowly, if you take tPA more than 4.5 hours after having a stroke you risk a vessel bursting and flooding the brain with blood. This can cause far more damage than the initial stroke.

To address this problem with tPA, scientists all over the world are trying to find better ways of treating stroke. In my research, I’m looking at anti-inflammatory drugs. You might think that this sounds strange, and that inflammation has more to do with arthritis and sprained ankles than it does with stroke. In fact, after a stroke your brain becomes really inflamed, and this can cause more damage than the initial loss of oxygen.

Think of the nasty pus you see around an infected cut or in a spot that you can’t resist squeezing. This pus is made up of white blood cells, which are like the body’s army for fighting infection and injury. There are loads of different types of white blood cells, and the ones I’m interested in are called neutrophils.

Normally, there aren’t any neutrophils in the brain because they’re kept out by a strong wall-like structure called the blood-brain barrier. After a stroke this barrier gets damaged, and over the following days more and more neutrophils get into the brain. Although neutrophils are normally important in fighting infection, in the brain they can be damaging and release substances that can break down the barrier even more. Like a domino-effect, this lets more neutrophils get in, and the damage keeps progressing.

For my research, I’m looking for ways of stopping neutrophils getting into the brain after stroke so we can limit the on-going damage. The drug I’m testing acts like a bouncer at the blood-brain barrier and stops neutrophils being able to pass through. There’s lots of evidence suggesting that stopping neutrophils might help people have less brain damage and make a better recovery after stroke.

Although lots of scientists like me are trying to make better drugs to treat stroke, like with anything, the best cure is prevention. Young, fit and healthy people don’t tend to have strokes. Normally, stroke patients have other things wrong with them like high blood pressure, diabetes, high cholesterol and obesity. All of these conditions cause an inflammatory response in the body, meaning there are more neutrophils and other white blood cells hanging around. If you have a stroke now, the additional inflammation caused on-top of this can cause devastating damage to the brain.

Stroke patients who also have diseases like these are more likely to die or become disabled. That’s why trying to limit inflammation is important, and that’s why my research matters. So if you’re reading this in Metro, sitting on the bus and eating a packet of crisps, maybe consider ditching the crisps and getting off a couple of stops early. Trust me, your brain will thank you.

Hannah Buggey

Hannah is a PhD student in the Brain Inflammation Group, which is part of the University of Manchester’s Faculty of Life Sciences

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