Podcast – Vascular Brain Health Science

Voice Over:

Welcome to the NIHR Dementia Researcher Podcast, brought to you by dementiaresearcher.nihr.ac.uk, in association with Alzheimer’s Research UK, and Alzheimer’s Society. Supporting early career dementia researchers across the world.

Dr Fiona McLean:

Hello. My name is Dr. Fiona McLean, and I’m really excited to be hosting this Dementia Researcher episode on vascular brain health. I am particularly happy to be hosting this episode, as I’m a postdoctoral researcher at the University of Dundee, where I investigate how metabolic diseases, like obesity and type two diabetes can lead to diminished brain function, with a specific focus on the blood–brain barrier. Today, I’m delighted to be joined by three other researchers in the field of vascular brain health: Dr. Gaia Brezzo, from the University of Edinburgh, Dr. Sophie Quick, who’s also from the university of Edinburgh, and Dr. Josie Fullerton, from the University of Glasgow. So now, I have done a quick introduction. Let’s find out a little bit more about each of our researchers. So Gaia, would you like to introduce yourself?

Dr Gaia Brezzo:

Sure. Thanks Fiona. So, yeah I’m Gaia, and I currently work at the Dementia Institute here in Edinburgh. I’m in Barry Nicole’s group, and I’m particularly interested in the immune response following stroke, and how this affects extracellular matrix, but also the immune system. So I will particularly be looking at what happens to monocyte-derived macrophages following stroke, and how and when they infiltrate the brain, and what happens to them in terms of do they become more microglial phenotype, do they leave after the stroke impact is resolved, and also interestingly, we want to look at how we can manipulate this response to improve cognitive outcome and prevent dementia.

Dr Fiona McLean:

Amazing. Thank you for sharing that. Let’s find out about our next researcher, Sophie.

Dr Sophie Quick:

Hi, I’m Sophie. Last year, I finished my PhD with professor Anna Williams, and now I’m doing a postdoc with her following that, the last year. I’m interested in something called cerebral small vessel disease, which is actually the leading cause of vascular dementia. And I’m particularly interested in the endothelial cells. So these are the cells that line the walls of the blood vessels in the brain; in all vessels, but I’m particularly interested in the ones in the brain, and how these cells interact with other brain cells, and how that might lead to what we see in dementia.

Dr Fiona McLean:

Amazing. I’m also a big fan of endothelial cells, which is maybe a bit sad, but I love them. And last but not least, Josie. Would you like to introduce yourself?

Dr Josie Fullerton:

Yeah. So I am Dr. Josie Fullerton. I work at the University of Glasgow. And in the last two days, I’m going to be finishing up my project with Dr. Lorraine Work. We focus on extracellular vesicles and microRNAs and their role in stroke. So basically, we’re looking at these tiny little vesicles that transmit messages to and from cells. And we’re looking at how these messages change after stroke in human in vivo and also in vitro; so the same models as well. And then from Friday, I’ll be concentrating a little bit more on hypertension, and how that can affect extracellular vesicle messages, and then how we could use that to treat… extracellular vesicles, how to treat hypertension. And that’s for Stewart Nicholas at University of Glasgow.

Dr Fiona McLean:

That sounds good. So you’re sort of almost broadening your sort of vascular interest. And yeah, that’s actually-

Dr Josie Fullerton:

Yes, I’m trying to learn a little bit more about vessels.

Dr Fiona McLean:

Lots more about vessels. Well, that’s helpful because we’re kind of going to be talking about that today. So now that we know everybody and we know what everybody researches, let’s start discussing a little bit more in depth about vascular brain health. So I think a good place to start is talking about what vascular brain health is. If you talk to the public about good vascular health, they tend to automatically think of the heart. So what do we mean when we talk about vascular brain health, and why is it important? Who would like to go first on this one? So Sophie, you look like you’re ready.

Dr Sophie Quick:

Well, I often think that people forget that the brain is highly vascularized. I think that sometimes, when we talk generally about keeping the body healthy and keeping the blood flowing and exercising and all of these things, we think about the benefits for the muscles, and we think about the benefits for other parts of our body. But I think people forget that the brain is full of… It’s like an incredible network of vessels. And the energy demands that the brain has is the highest organ in the body, I think. I think I’m right in saying that. I can’t remember what the percentage is, but-

Dr Fiona McLean:

I think in oxygen it’s… I think it uses around about 10% of all, all the oxygen.

Dr Sophie Quick:

So [crosstalk 00:05:17].

Dr Fiona McLean:

I can’t remember. Yeah, the other stat that I have in my head is that the total length of capillaries in the human brain is about like 400 miles or something. Although maybe, I think that wasn’t a paper. It wasn’t an official paper. But it-

Dr Josie Fullerton:

We worked out it was too long to run too long. We were trying to find a good brain health to do a fundraiser for. [Crosstalk 00:05:42] you can’t run the length of the vessel.

Dr Fiona McLean:

I know. It’s very, very true. And within those 400 miles, all that, the main thing that’s happening there is oxygen and nutrient exchange. So yeah, absolutely. Gaia, what do you think?

Dr Gaia Brezzo:

Yeah, just to add from what Sophie said, I think you could probably think about your brain as a very specialized muscle, so like the heart. Obviously, it contains vessels as well as other cells. So they do a really good job to keep you healthy. So as Sophie touched on, if you’re exercising, it’s as good for your brain as it is for your heart. And again, just to reemphasize what Sophie said, the body is all connected. So of course what happens below the neck is a reflection of what is happening above the neck and also vice versa. So I’d say it’s extremely important to keep the whole system healthy and happy, really.

Dr Fiona McLean:

Absolutely. And Josie, do you have any take on that, especially now that you’ll be looking, more broadly at sort of vessels in your new postdoc?

Dr Josie Fullerton:

Yeah, so I do think one of the things, when we’re talking to the public, I think if we say vascular brain health, they would just focus on the brain health side of things. As in they maybe focus a bit more about the mental health and wellbeing aspect. So when we then add in vascular brain health, I do think that it could be quite confusing, in the sense that we are still talking about mental health, but also your physical health. And like you say, Gaia, it is like a muscle and it has to be exercised. But I don’t think people maybe put the vascular and brain health together on a day-to-day basis.

Dr Fiona McLean:

I absolutely love that point that you’ve just made. I think you’re completely right. In terms of what we talk about as health, I think it’s the only organ where we talk about a physical health and a psychological health. You don’t think of the rest of your organs. You only think about physical health. And I guess that’s maybe where it becomes quite complex. But in some ways, the two are very interconnected, because if you don’t have good physical brain health, that can impact on the psychological side in terms of cognition, memory, mood. So, yeah that’s a really good point I never thought about before, where the public maybe needs a bit more information on how these are actually two separate things in terms of what we’re talking as health, mental health and physical health, but actually they’re interconnected at the same time.

Dr Josie Fullerton:

Totally. And I just think it’s so important too, when you’re thinking about the things that you can do to improve your health and your mental health. It does relate all back to vascular health, especially in the brain.

Dr Fiona McLean:

Yeah. The vessels in your body are everywhere. And I guess that’s why we’re talking about vasculature in the body. We need to remember that. And remember that they’re all connected. It’s kind of, in a way, apart from your nervous system, how your organs are connected to each other, is that through the vessels. It’s really cool.

Dr Fiona McLean:

So I think one of the things I find most interesting about the brain vasculature is, despite the fact that we do have vessels everywhere, the vasculature in the brain is actually very different to the rest of the bodies, in that it has something called the blood–brain barrier. So does anyone want to just give a quick rundown of what the blood–brain barrier is, and what is it about it that makes it unique? So who? Sophie, again you’re nodding. I’m going to pick on you.

Dr Sophie Quick:

I guess I must just have the look that I’m eager to say something always. Yeah, when I first started my PhD, I had not done a huge amount, even of neuroscience before. And I particularly hadn’t really thought much about the vessels of the brain. So starting the PhD itself, five years ago or whatever it is now, I was really fascinated to learn about the blood–brain barrier, which is maybe something that I hadn’t really given much thought to. And I mentioned that I had studied the endothelial cells. And so, I think they’re really special. I think they’re really special, especially in the… So in the brain, they have the vessels that are formed of these endothelial cells, and they have these specialized functions. So you’ll find endothelial cells all over the body. But in the brain, they have these really special functions, which means that they can form a kind of tighter seal. So they have different things on their surfaces, which means that they’ll lock together a little bit better, that sort of thing.

Dr Sophie Quick:

So, that’s a very sort of first level thought of the blood–brain barrier in terms of the endothelial cells. And then there’re different cells that sit on the surface, and then they can interact with other brain cells, so you can get this kind of a little bit of a conversation between the rest of the body and the brain. But generally, the blood–brain barrier, provides kind of a seal, I sometimes think of it as. You have this network of blood vessels throughout, but you want to protect this very specialized organ, no matter how demanding it is. You want to protect it from things that get carried in the blood, because I suppose it’s the best way to protect that brain health.

Dr Fiona McLean:

Yeah, from things like viruses, obviously when we’re thinking about the world right now, COVID, is very prevalent. So yeah, that blood–brain barrier is so important for protecting the brain from viruses, as well as other toxins. I think your idea about the seal is right. I always think about endothelial cells like a bouncer on the door of a nightclub, and they kind of decide what gets in.

Dr Josie Fullerton:

Not today, if you’re [crosstalk 00:11:32].

Dr Fiona McLean:

Not today. They decide what gets in, but they also chuck any rubbish out as well. I always like… I think maybe I’ve got this nightclub analogy in my head about cells in the brain, because I always think of the microglia as they’re the ones who would clear it out. They would carry your shoes home after a night out.

Dr Sophie Quick:

I have often thought about… I’ve often thought about the characters, given there’re little characteristics to different cell types. I think of… Yeah, I think of endothelial cells as quite steady, they just kind of get the job done. But if it’s something else wrong with them, you’re really going to know about it, I think.

Dr Fiona McLean:

That’s so good. So yes, that’s why we’re talking about the blood–brain barrier and why it’s important, and why it’s unique. So Gaia, do you have any thoughts on that?

Dr Gaia Brezzo:

Yeah, I think, just to add on what Sophie said again, because she described it beautifully, I’d say, yeah it’s super selective. But I think what’s really exciting about blood–brain barrier research, just in general, is that we’re still discovering more and more about it. We know that it’s an incredible structure. As we said, it keeps terrible things out, puts bad things out, but we still don’t really fully understand even in disease, if it’s damaged, if it’s weakened, what really happens mechanistically, or even other cells that maybe you might not think directly interact, like microglia. There’s more and more evidence to show that they do. So I think it’s just a really exciting field of research, that will hopefully lead to new discovery in terms of how we can use the blood–brain barrier to really improve people’s lives in terms of recovering from dementia or even preventing dementia entirely.

Dr Fiona McLean:

Absolutely. Yeah, the one thing that we do know is that the blood–brain barrier goes wrong in dementia-related diseases, and it happens pretty early on, in terms of that sort of progression. So, finding out more about how it works and why it goes wrong, when it goes wrong, is so important. I think that other… Like the thing that always strikes me though is why does a blood–brain barrier equivalent not exist so much in other organs? I think that just shows how controlled the brain really is. I think the only other one I can think of is the placenta. I think if you look at… which is quite maybe something you wouldn’t associate with, but the placenta also has this really unique barrier. And I guess when you think about it, if it’s trying to protect a baby, that’s something really precious in your body as well. But yeah, Josie, what would you think on this special barrier?

Dr Josie Fullerton:

Yeah, so I think, Sophie, you summarized that beautifully. In my notes, I wrote, “It won’t let things cross.” So you’ve done much [inaudible 00:14:14]. So one of the things that… I’m just going to do a bit of our research plugging, is we’re looking at extracellular vesicles because they do cross the blood–brain barrier. So we’re looking at them as a method of treating things like stroke or Alzheimer’s disease or TBI. We’re looking at how we could administer them actually intranasally, or as my boyfriend puts it, you’re giving rats nose sprays, which isn’t what we’re doing. But yeah, what I’m really interested in about the blood–brain barrier is how selective it is and what it does let to cross, and when it does go wrong, when it is leaky, it’ll let things through that. So it’s obviously disrupting the brain’s happiness, but yeah, I think it’s also important to think about what we are, what our blood–brain barrier lets through in normal conditions. So yeah, just to add on, a little bit [crosstalk 00:15:12].

Dr Fiona McLean:

Yeah, absolutely.

Dr Sophie Quick:

Also, I was going to add-

Dr Fiona McLean:

Sorry, Sophie.

Dr Sophie Quick:

I was going to add, I also think that we have a tendency to think of the blood-brain… any vessels as kind of tubes. And I think what you were also saying, Josie and Gaia as well, that the vessel is more than just a carrier of blood. It, in itself, is quite dynamic, and in itself can go wrong, and the cells and things, they also have an effect, which I think, like you said, Gaia, is a really sort of exciting area. In the past, I think we used to just think, “Oh, it’s just carrying the blood, and gets a hole in it and it goes everywhere.” But it’s so much more than that. Like the cells themselves really have their own, I guess, personalities, like we were saying. But they really have a role themselves, which is really cool.

Dr Josie Fullerton:

The other thing, going on from what you just said, Sophie, is that they used to think that the brain wasn’t important, and that the heart was the center of the being. And I think it was… Was it [Descartes 00:16:07]? It was a philosopher anyway. He thought that the brain was just a valve, a heat for the heart. And realistically, the brain is an important thing. And I think, yeah it’s just amazing to think of how things have changed across history and philosophy.

Dr Fiona McLean:

Absolutely. I think also there’s definitely this shift as I think everyone sort of said away from sort of just thinking of these vessels as tubes, and also actually they’re really important brain cells. And I think one of the things that highlights that to me the most, is it’s something like nearly every neuron in the brain has its own capillary, and that shows that even the neurons themselves, they can’t function by themselves. I think historically through neuroscience, we’ve put a lot of emphasis on learning about neurons and kind of everything else has just been to the side.

Dr Fiona McLean:

And now I feel like we’re in a real sort of interesting time, where other cell types are now coming to the forefront of research, your microglia, astrocytes, endothelial cells. And we’re starting to understand that really, there’s a whole heterogenous population of cells out there that work together to make the brain work. They can’t work independently. And I think that’s what makes sort of neuroscience really exciting at the moment. So yeah, we’ve done been discussing a lot about how important our brain blood vessels are. But what types of problem and illnesses can arise from having poor vascular brain health? Because some people aren’t always aware that actually these diseases can be a result of the vessels in the brain. So let’s discuss some of that.

Dr Gaia Brezzo:

I can kick off maybe this time, save Sophie. Sophie’s [crosstalk 00:17:51] from like, “Not me again.” Yeah, I’d say… I was thinking about this and I was like there’s not really one way to put it. So I think if you’re talking about damage to the vascular system, I think it’s multifaceted in general. And then depending on what disease you’re talking about, also changes. So talking about my own research, so something like a stroke can cause quite a quick change to the blood–brain barrier. So of course there’s a clot that could occlude the vessel, and this could either lead to [inaudible 00:18:22] if it ruptures and causes a hemorrhage, or it could be something that, I guess it’s more eerie because it’s more slow-building like or cerebral amyloid angiopathy. So you don’t really know it’s happening, but when it does, it obviously increases your predisposition for stroke.

Dr Gaia Brezzo:

So I’d say it’s very different depending on what condition you’re studying, and also within your condition. So again, going back to stroke for me, even though there’s this really big insult at the start, following the resolution of this, we see a lot of angiogenesis. So new blood blue… Oh, I’ll start again. Is that we see angiogenesis following the stroke resolution. So we see a lot of vessel changes. There’re new vessels that sprout, trying to basically make up for the fact that that area has been deprived of oxygen, but also these vessels look quite different. So there’s still a lot of changes within stroke progression, but also on resolution, that we still don’t really understand… Sorry, I went on a bit of a tangent there, but…

Dr Fiona McLean:

No, no.

Dr Gaia Brezzo:

… basically, diseases look different.

Dr Fiona McLean:

Diseases do look different. I actually think… One of the misconceptions about brain health in general, when you think about sort of dementia related diseases and illnesses, is that everything fits into a category. But actually, most patients have a crossover, or have multiple conditions or illnesses. And that’s something that makes it really complex. And trying to unravel what’s connected, what’s independent, is obviously very difficult. But yeah, let’s talk more. Like Sophie, what’s your kind of area of research in terms of the brain and problems that can arise?

Dr Sophie Quick:

Yeah, well I guess in contrast to what Gaia was saying about something like stroke being a very of-the-moment kind of injury to the brain, that’s then going to cause a long term effect, in terms of dementia, during my PhD and now postdoc, I have been looking at cerebral small vessel disease. And well, we understand what we see in the vessels. They have this very characteristic changes. And then you see, on MRI scans, you can see like these sort of hyperintensities which is just sort of like spots on the MRI. And so we kind of understand what goes wrong in the vessels, and we kind of understand what goes wrong in the other cells of the brain. So like the neurons and the cells that wrap around the neurons, the oligodendrocytes. So we kind of see and understand what’s going on with them, but not really understand how the two are linked.

Dr Sophie Quick:

And so I think, yeah cerebral small vessel disease, I’d never heard of it before I started studying it really. It was just a project. And I loved working with Anna Williams, and the topic was so interesting. And yes, it’s kind of like a slow burn rather than a specific thing. And exactly what you were saying as well, Fiona, about this overlap of different features. Like cerebral small vessel disease is really hard to diagnose. You can tell it a bit better with an MRI scan, because it has these characteristic features. But the things that a patient would present with, are things like an unsteady gate, some cognition problems. So like simple forgetting. And these very much overlap was sort of just what people call normal aging, whatever that is. And so it’s going to be really difficult to diagnose. And-

Dr Fiona McLean:

And also if you think about gate and cognition, you probably think about Parkinson’s…

Dr Sophie Quick:

Yeah.

Dr Fiona McLean:

… quite quickly, just because that’s had a lot more awareness around it. So yeah.

Dr Sophie Quick:

Yeah. So people don’t really understand, but for people, it’s under-recognized, I suppose, and then also under-diagnosed. And so we’re sort of getting a little bit more understanding of it now, thanks to some big researchers who’ve taken the time on this, but yeah.

Dr Fiona McLean:

Yeah. That’s so important, because if you want to treat these things, you have to be able to diagnose them first. So it’s that thing of how can we even begin to treat something that we can’t diagnose. So yeah, I think you’re right, and that is so important to be able to do that. Josie, what about you? Would you like to talk a bit about sort of the diseases that you are researching and have researched in the past?

Dr Josie Fullerton:

Yeah, of course. So right now, I’m probably sort of in between Gaia and Sophie, in that really stroke and small vessel disease. So I won’t focus too much on that. Obviously, there are two different types of stroke: hemorrhagic and ischemic stroke. So there’s slightly different things that go wrong in the vasculature to cause a stroke, hemorrhagic being a leak, ischemic being a blockage of some form of clot. So I think that’s quite important to convey to the public. But also, there are, aside from stroke and small vessel disease, I previously worked in dramatic brain injury at the Glasgow TIB Archive. So obviously, there’s brain injuries such as falls, road traffic accidents, assaults, but then there’s also sport related injury, which is always in the news in the media [inaudible 00:23:45] retention. So I think it’s very important to think of our brain health in the sense of TBI as well.

Dr Fiona McLean:

Absolutely. I think I have quite an interesting take on it, in that I look at diabetes and obesity, which have classically being thought of as very sort of a rest of body illnesses. If you talk to the public, they maybe know about the pancreas, they definitely know usually that in type two diabetes, you have to control your blood sugar. But I think it’s taken a while for people to actually start to recognize that sort of uncontrolled glucose levels in your blood, also affects your brain. Because as we’ve been talking about your vessels aren’t just in your body, they’re actually all the way everywhere, and all up into your brain as well. And I guess I sit in the field almost before all of you, where I’m kind of looking at your life choices that you make sort of earlier on in your life, and how that might set you up to go on and develop some of these diseases. So actually, we’ve got a nice little cohort here, collaborations I think. Josie.

Dr Josie Fullerton:

I just would like to ask you a question, Fiona, if it’s alright to ask you questions.

Dr Fiona McLean:

I thought I was sharing.

Dr Josie Fullerton:

No, this may be edited out later, but you know how your blood vessels and your periphery accumulate fat and become stiffened and hardened and things like that? Does the same happen to your brain vasculature in relation to diabetes?

Dr Fiona McLean:

Yeah.

Dr Josie Fullerton:

Yeah?

Dr Fiona McLean:

Yeah. Yeah, everyone’s nodding as well. So, I got [crosstalk 00:25:24].

Dr Josie Fullerton:

That’s just me.

Dr Fiona McLean:

No, no, no, no, but that’s the thing like, unless you sort of touched on that metabolic disorder thing. You should, it’s a fun field.

Dr Josie Fullerton:

We’ll collaborate, darling.

Dr Fiona McLean:

We’ll collaborate. But yeah, absolutely. But you’re in science. And even within science, it’s taken quite a long time for us to appreciate that obesity and type two diabetes, isn’t just about putting on weight and your pancreas having trouble, and your heart having trouble and your blood glucose levels going up, and your insulin not being as effective. All of that impacts your brain as well as the rest of your body. I think it’s because your brain is contained in your skull. That’s where all our inputs are, like your vision’s up here. And I think you forget, your brain is an organ. It just, it’s your control center. So if there’s stuff going wrong in the rest of your body, the likeliness is that your control center’s having problems as well. It’s really, really likely.

Dr Fiona McLean:

And that’s why I find it really exciting about the blood–brain barrier and type two diabetes and obesity, because what we’re finding is that those conditions, those illnesses, which are driven by lifestyle choices throughout your life, are having a massive impact on your blood vessels, the blood–brain barrier. And actually, what I think is a really hopeful message, is that if we can start explaining more about how, if you make healthier choices, that you can protect your brain, then what we might see is that people will make healthier choices not just for their whole bodies, but their brains as well. And it means that we might be able to reduce how many people are going on to develop dementia-related illnesses later in life.

Dr Fiona McLean:

And that’s really powerful, because that’s something that we can all control. We can control our diets, we can control how much exercise we’re doing, whereas once you sort of get further down the line into these illnesses, there’s limited therapeutics. A lot of them have no cures. And that can make people feel quite hopeless and things are out of their control, whereas we can control these things earlier in our life, and that should be empowering for people, I think. So-

Dr Gaia Brezzo:

Just that, I want to add… Oh, sorry [crosstalk 00:27:48].

Dr Fiona McLean:

No, Gaia, on you go.

Dr Gaia Brezzo:

Yeah, just because I was just thinking like, again I know nothing about the periphery, shamefully. I am very much above the neck researcher, but also thinking about something like surprise-surprise, I also have a background in small vessel disease, we do know even in human postmortem brains that the vessels do become thicker, and they’re a lot stiffer. But then in my first postdoc that I did, I worked on a monogenic form of small vessel disease. So it was a collagen IV mutation, which is a protein that lines the basement membrane, so then going back to the actual core vasculature.

Dr Gaia Brezzo:

And I found that there’s actually thinning of the basement membrane. So even though they might be similar in terms of the small vessel disease or one might be sporadic or one might be myogenic, but they’re still quite different in terms of how the vessels change. And I think that’s quite important, in terms of thinking about mechanisms and what might be different, why is one thicker, and one is smaller, what’s happening to the endothelial, what’s happening to the smooth muscle cells and how all the neuroglial vascular cells might influence which way it goes, depending on sporadic or monogenic forms of small vascular disease.

Dr Fiona McLean:

And that is what you should set your lab up to do.

Dr Gaia Brezzo:

Yeah. Well, we’ll give it a go.

Dr Fiona McLean:

Any funders out there. So, as we’ve been talking, we’ve been talking a lot about how there are quite a mix of things that can go wrong with the brain vasculature. So what are… Let’s try and pinpoint now, what are the challenges of distinguishing between these different illnesses, that are linked to poor vascular health, and what can we do in the scientific community to try and unpick those?

Dr Sophie Quick:

I guess, I was just going to speculate; I don’t know if that I have any sort of conclusions, but I was just going to speculate that I think that one of the big challenges you have as a brain researcher is the skull, and the sort of impenetrability, and the ability to… you can’t take a sample or do a scan even… Well, they have these incredible… Here in Edinburgh, there’s great MRI groups that do really beautiful work, and only kind of through this work, do we have a better understanding of this sort of thing. But you are limited with what you can do to research a living brain really. And yeah, I think that makes it quite challenging. So we have to use other creative ways, perhaps studying the cells in a dish or using perhaps the animals that can represent the diseases that we’re interested in. But I often think that is one of the challenges, broadly, as a brain researcher. But yeah.

Dr Fiona McLean:

Definitely. I also think it’s a challenge sort of in drug development as well, is being able to get your drugs into this highly protected area. And it’s interesting talking to some people who are in sort of industry, and they say, “Well, is a leaky blood-brain barrier really a bad thing? Because then we can get our drugs in.” But I think there’s only now, again, this sort of developing, this sort of understanding of actually what might be really good is if we just keep the blood–brain barrier or not leaking and functioning. That kind of means that maybe you don’t need any drugs to treat anyway, because there’s nothing going wrong or not as many things going wrong since the blood–brain barrier becoming leaky is such a sign of problems.

Dr Sophie Quick:

I was going to say it was really interesting what you were saying before, Josie, about your work that looks at the extracellular vesicles as a sort of a non-invasive way, as opposed to… I suppose it is still invading the brain, but in a non-invasive way, crossing the blood–brain barrier. Using that, I think that’s a really incredible idea kind of using the endothelial cells sort of intrinsic properties to manipulating them in a way that we can maybe use it as a treatment. That’s a really cool idea.

Dr Josie Fullerton:

Yeah. We’re really excited by it, I have to admit. And one of the things we, in theory, have down the line is that you’d technically be able to take some of the patients’ own blood, spin it down, just so that you’ve got the plasma, isolate the EVs. You’re then giving the patient back their own extracellular vesicles. You’ve just alluded them with the drug. This is obviously quite far away from my work right now, but that’s sort of the long term goal.

Dr Fiona McLean:

But long term goals are where it needs to be, right? If you want that to happen…

Dr Josie Fullerton:

We got that. We’ve really-

Dr Fiona McLean:

… you’ve got to have that in mind. I think that’s so cool. So in that way, is the reason behind doing that, so that there’s less of a reaction by the body, and to sort of reject the therapeutic?

Dr Josie Fullerton:

Yeah, exactly. And so there’s been a lot of work in extracellular vesicles recently and they are a key modulator in cell to cell communication. And they are released in health and disease, and they do go from sort of one cell to another, but it’s just, we’re trying to figure out how you could maybe target it a bit better, because extracellular vesicles kind of do their own thing. We’re not really sure exactly where they come from. Although we’re isolating them from plasma in a stroke patient, they might be extracellular vesicles from the brain. It might be a waste product from the brain that’s been kicked out, and we’re taking it and loading it. So things like that we [crosstalk 00:33:26].

Dr Fiona McLean:

Are extracellular vesicles on the night out, in our nightclub that we built? Are they your friend that goes absolutely rogue, and they’re just going everywhere, and you’re like, “Come back”?

Dr Josie Fullerton:

They could be that. I will see… I like to think of them as like the person that leads you astray.

Dr Fiona McLean:

They’re not just going off on their own, they’re taking you with them.

Dr Josie Fullerton:

Let us go to them. They’re bringing you there as well.

Dr Fiona McLean:

So back to the science side of things, can you basically put anything in an extracellular vesicle? Is it like a Trojan horse, you can just put anything in there, sneak it in?

Dr Josie Fullerton:

Yeah, so in theory, what we do is we electroplate extracellular vesicles. So basically-

Dr Fiona McLean:

Oh, that’s a tongue twister.

Dr Josie Fullerton:

Isn’t it? So we’re giving them a little electric shock, which opens up their membranes so that we can put messages inside. So right now, we’re using microRNAs. But in my project, that I’ll be starting on Friday, we’ll be delivering a peptide. So the idea is that it could be used as a vehicle. The other sort of good thing about extracellular vesicles is that you could use them as a biomarker. So in theory, somebody’s presenting stroke-like symptoms in A and E. Right now, it’s so challenging to try and diagnose stroke on arrival to hospital. So in theory, what we could do is take a blood sample from the patient, and we could run it through. And if they have these particular markers, we would know that they’ve had a hemorrhagic stroke, or there’s a stroke mimic, or there. That’s the idea, the big picture.

Dr Fiona McLean:

That’s cool. So I have two questions. One, what are the primary cells that release extracellular vesicles, in sort of just a normal functioning brain? I’ll let you answer one first, actually.

Dr Josie Fullerton:

Yeah.

Dr Fiona McLean:

Yeah.

Dr Josie Fullerton:

I was at question two. So it was interesting you said that. So we recently put together a review. And what was interesting was when I tried to find a nice summary of all the cells that release extracellular vesicles, it was really difficult to find a nice distinct vesicles because they’re quite new and exciting, and people are into their own sort of field, nobody truly summarized actually the vesicles in total. But when you look at the cell specifically in the brain, it is pretty much every single cell type in the brain. If you Google like MEG [inaudible 00:35:43], oligodendrocytes brain, and EVs, they release them. The problem is that technically, we wouldn’t be able to isolate them from the human brain, a bit like what Sophie’s saying. It’s protected by the skull, which is why we’re looking at circulating extracellular vesicles rather than the brain releasing vesicles. So yeah, that’s what we’re doing, which is quite cool.

Dr Fiona McLean:

My second question is really a comment in that. So we’re talking about how extracellular vesicles are in the blood. Maybe that is a way how we can sort of start to pick apart these different illnesses that are linked to poor vascular health. And so maybe yeah, they’re a great marker for stroke. And I don’t know. Is there much research done on if they’re released in people who have other brain illnesses and diseases like Alzheimer’s or Parkinson’s, or? Does anyone know?

Dr Josie Fullerton:

Yeah, that’s a great point. So what we’ve been allowed to do with one of the funds that I’ve been granted, is through the NIHS and Diamond Fund, and we’re looking at microRNAs, that it carries extracellular vesicles or EVs, and their relation to vascular cognitive impairment, small vessel disease, frontal temporal dementia, dementia, and stroke. So basically, I’ve got a panel of 48 microRNAs that have been derived from EVs, and we’re looking at 400 patients, and the EV expression after stroke and without stroke across all these patients. So the data has been produced. The data will be analyzed. Considering I start the job on Friday, tomorrow’s going to be really busy.

Dr Fiona McLean:

You can analyze that, all that data in one day tomorrow.

Dr Josie Fullerton:

Yeah. I’m just going to finish here, and then I’m just going to borrow [inaudible 00:37:42] date guys. I’ve got to-

Dr Sophie Quick:

No sleep for Josie.

Dr Josie Fullerton:

No sleep.

Dr Fiona McLean:

Actually, that’s really exciting. Yeah, it sounds like a possible. I think what we’ll probably have to think of in the future is not just sort of one diagnostic, like other illnesses have, but I think for the brain, we need that sort of multi-approach. So maybe we’ll have another blood biomarker alongside extracellular vesicles, alongside brain scans. And maybe together, you’ll have this panel of diagnosis that you go through, and that you’ll be able to say, “Right, this is likely what you’ve got, or this is what you’ve got,” that’d be great, if you could definitely say it was that. And then you would get your treatment plan to help you battle that illness or that disease, or even better, let’s say cure it. That would be… Because that’s what we’re all aiming for. We’re aiming to cure these diseases. So yeah, I think, yeah that’s… At least, even though it feels like it’s been a battle to get here with diagnosis for different brain illnesses, I think it’s definitely positive. And I think as long as the funding keeps coming, we can definitely get there as scientists. So, I’ll-

Dr Gaia Brezzo:

I think that’s the… Sorry Fiona, I say that probably the key bit is the funding keeps coming. I think vascular research has been underfunded, just generally.

Dr Fiona McLean:

Yeah.

Dr Gaia Brezzo:

And hopefully, we’ll see a bit of a boost.

Dr Fiona McLean:

I completely agree.

Dr Gaia Brezzo:

Because also thinking back… Yeah. Even not just to keep banging on about stroke, but we tend to maybe think about stroke as like, for example, if the blood-brain barrier opens, or if monocytes are infiltrating, it’s either good or bad, but there’s actually more evidence to show that it’s a lot more subtle, than obviously just saying like, “Oh, we’ll just prevent all the monocytes to come in.” It actually makes things worse. So I think it’s important to not think about it, maybe just in black and white, and to try and get all the subtleties, which is obviously they’re a really hard thing, which is why we need more money.

Dr Fiona McLean:

Yeah. I think funding and I think Alzheimer’s Research UK has been aware that this is a growing area. And actually, recently speaking to the British Heart Foundation, they definitely are starting to recognize that vascular brain health needs more support. There’s a lot of work that can be done there. So I think it’s definitely moving towards sort of getting more funding, which is really exciting, and needed. And I think we can do a lot of clever work there. Josie.

Dr Josie Fullerton:

I keep forgetting the point that I was going to make, and it’s come back now. So just when you’re thinking about funding and challenges, I think one of the biggest things for women in research here, is vascular diseases, especially in women. I think often, we’re using animal models. Most animal models are male. And then most drugs that go to the clinic, have been based on these animal models, which are male, and it’s not necessarily treating the same conditions that are presented in women. So we have to be really careful, for instance, with our study. Extracellular vesicles can just be different, depending on sex. It can also be affected by age and smoking and everything else. So there’s lots of different factors we have to take in mind. But I do think funding-wise, we do need to think about targeting these kinds of pathologies and diseases from a male and female approach, if possible.

Dr Fiona McLean:

I think that there is a lesson to be learned from heart attacks, where heart attacks present differently in men and women. And for a long time, because a lot of the research was based on men, a lot of women would go to emergency rooms and be presenting, not typically thought of as heart attack symptoms, and be sent away or not be treated correctly. But again, that is changing. And I think, if you think about it, if the vessels in the… If your heart and is sort of what we think of as vasculature, if that presents differently, then the chance of the brain vascular presenting differently is probably quite likely as well. Gaia?

Dr Gaia Brezzo:

Yeah, I was just going to say, it is changing. So I don’t know if any of you saw, the MSC brought out a call specifically saying that they now kind of expect you to do multi-sex studies, which is really good. Because I think the stickler for me has always been, you know you should do it. But you’re so restricted on time and money, and the fact that there’s only really short postdocs or there’s only maybe one person working on it. It’s just so difficult to get everything done and properly power it as well. Because if you try and do it, but you don’t do it well, then it’s worse than not doing it. So it’s nice to see that reflected in funders, because that will encourage people to do it and recognize as being something that we do really need to do.

Dr Fiona McLean:

It is interesting. So, I feel it’s very much though it has to be recognized, not just by saying it loud, but it has to be recognized in action as well. So, if anyone from the MRC is listening, we love this. We think it’s great that you think that male and female mice or human tissue needs to be looked at, but you got to fund it, because it’s going to cost you more. So you got to fund it as well, and yeah, time as well. It’s just got to be appreciated that it’s going to take more money, more time, but I think it’s worth doing. We’ve just talked about it.

Dr Fiona McLean:

So I do a little bit of peripheral vascular investigation, shall we say. So I do a technique called laser Doppler imaging in the periphery. And I do that in mouse models. So basically, it gives you a scan, and you can use some math’s to work out the blood flow rate. And just doing controls in male and female mice, so just normal C57 mice, the blood flow rate of the female mice is just slightly higher, and this is unpublished. So I’m just talking off the cuff here a little bit. But even though that was a very small study and it’s just one thing that I’ve taken away from it, it kind of shows there maybe is something different happening here. Whether it matters or not, in the diseases that we look at, we don’t know. And estrogen, which women have, which men don’t have in the same way, could be playing a factor too. So I guess it does become more complicated in that we need to look at aging and sort of hormone levels as our sort of whole, not just isolated factors.

Dr Sophie Quick:

Yeah. I think the idea of differentiating and segregating the data, presenting it as male and female as well as together, I think is really important when you are looking at animal study or even human tissue, as you say. I think it’s really important because they present so differently. Like I think for example, it’s been known for quite a long time that microglia, the tidier uppers of the brain-

Dr Fiona McLean:

The ones that are carrying your shoes home from the night club?

Dr Sophie Quick:

Exactly. They’re going around, but they’re in everyone’s business, they’re clearing this up, they’re tiding that, touching this, touching that, whatever. But I think it’s known for a while that they do behave differently in males and females. They are different. Maybe, yeah one, I can’t think of what exact features they are, but I think they behave differently. And so if you are only going to study one of the sexes of animals, you’re going to miss something. You’re going to miss something, like you say, and then you take that information and then you carry it forward to a drug trial. And interestingly, often drug trials are only males as well. A human drug trial, would often just have a man, a male cohort, because they don’t have those crazy hormones.

Dr Sophie Quick:

So typically, you might get your stage one safety trial just using them, which then you’re going to translate them as you say, these vascular diseases are more common… well, as common in women, if not more common. And then you roll it out to a bigger group of people, of males and females, and surprise, it doesn’t work. So yeah I think the idea of starting early with that, will be really beneficial in the long run. So it might require more investment early on perhaps, but you could try and say, “Well, it means you’re not going to drop it at the later stage, because you’ve covered all of your bases early on.” So it just makes more sense.

Dr Fiona McLean:

So I have a question, and this is something I’ve been thinking about, in terms of models and picking males and females. If you are looking at diseases of the brain, which typically occur in people who are older; therefore in women, it would happen postmenopausal, is it better to use a female mouse, who is maybe premenopausal, but obviously match his gender, or is it better to use a male mouse, which maybe has estrogen levels that are potentially closer, and other hormone levels are potentially closer to post-menopausal women? Has anyone ever thought of that?

Dr Gaia Brezzo:

Yeah, I think that goes back to how important aging studies are, and you can’t really get away with that. So all of these diseases that we’ve been talking to happen to individuals that are a fair bit older than the equivalent of what we tend to study pre-clinically. And it has many, many challenges, probably more than saying, “Oh, we’ll include young female and male participants, or even mice, but it definitely has to be done.” So I actually went to a really good conference a couple weeks ago, and there’s a group in America, which I immediately forgot the name of the PI, unfortunately. It’s normally my thing, that they have spent years and years optimizing aging models of stroke to the level where they were basically saying that they require so much care.

Dr Gaia Brezzo:

So these were like 21 to 20 months old. So if you think about a mouse lifespan, it’s about 24 months. These are very, very aged. And it came to the point where they basically have to wash them, because they get infections so pronely, because they don’t groom themselves as well. So, that’s something. Again, if we think about how many people physically work on a project, or how much money is needed, the scale just becomes so much more than anything that I’ve ever seen in the UK, for example.

Dr Fiona McLean:

Yeah. So I guess we maybe have to think about, do we do more studies in humans, and how do we encourage that, so that we are sort of modeling it better? Yeah, we need more money, probably a better way to recruit people as well. I think that’s one thing people really struggle with is recruitment. And I think the COVID 19 vaccine is a great example of how actually good, almost marketing, of studies and also support and funding; UK government, good funding can really accelerate these areas of research by getting more people in, so we can study these diseases in people before they develop the disease, and then follow them through, and see how their health develops as they get older as well.

Dr Sophie Quick:

Yeah. But I think we will always need something to study in the lab. I think the work that we can do in human studies is brilliant. And definitely, we could consider expanding that out, and thinking carefully about how we could use the technologies we have in that. But yeah, I think we will always need to be able to test it in something less, something on a smaller scale. So something that can link all of these different elements together, but something on a smaller scale before you start putting it into a human.

Dr Fiona McLean:

Yeah, definitely. I think a scientist in the field, we know that every sort of model has a pro and a con. So cells are really super important. It’s so important to have cell models. And I think the IPSE area is really interesting, because we’re getting closer to what human cells would and should look like in a dish. And then obviously, human studies, that’s where we’re all aiming for. But we do need that transition. We do need something that’s a go-between of whole organisms study. And I think we could do a whole extra podcast on models used in neuroscience and in dementia research. Gaia, on you go.

Dr Gaia Brezzo:

Yeah, I was just saying, I think it goes back to what Sophie touched right at the beginning, that SVD is so heterogeneous that it’s always very difficult to come up with a good model. I know that’s true for any model we have; obviously in my sense, it’s not the real thing, and we’re modeling aspects of it. But I think, especially for SVD, it’s particularly tricky, because we still haven’t really nailed down aspects that are like, okay these are key features. And one way is to go to monogenic. But then again, it’s only a very small percentage of what we see in the population. So, you still want to be modeling sporadic, which again, as the name suggest is very different in every person, which makes our job a lot more tricky, but keeps us in a job at the same time. So here.

Dr Fiona McLean:

If you look at the Alzheimer’s field, there’s over 150 models. And the way that I manage it in my brain, so that my brain can deal with it all, is that you really have to pin down your question, and be like, what question am I trying to answer here? What are the variables that affect that question, and then look for a model that has those variables…

Dr Sophie Quick:

Yeah. I think that’s-

Dr Fiona McLean:

… or that you can add into a model.

Dr Sophie Quick:

I think that’s exactly right. And just what you said there, Gaia, which was about several aspects. So like what is your question? What aspects are being modeled? And I think that when you’re thinking about these complicated diseases, Alzheimer’s, small vessel disease, stroke, you’re never going to perfectly recreate what you find in the human condition. You are always going to have to, I guess, compromise on something. And so it comes to understanding the aspects that the model offers, and really understanding what the question is that you’re asking. Because unfortunately, some animal research is necessary in the way that we have it at the moment.

Dr Sophie Quick:

And so, yeah I think that we have to start, you have to start with those things, understanding the models. And yeah, for example, the model that I have kind of characterized throughout my PhD, looks at small vessel disease, but it’s about looking at it without hypertension. So yeah, we’ve always thought that hypertension is super important in small vessel disease, and of course it is, but what does that disease look like without hypertension. So yeah, picking those aspects, moving forward with your question, I guess is one of the big challenges for starting any research, but yeah particularly with something complicated, like vascular health.

Dr Fiona McLean:

So moving on, I think for a long time, society, as I mentioned before, has been very aware of how our lifestyle choices affect our bodies, but we think less about how these choices affect our brains. So for anyone listening, what can we do to keep our brain vasculature healthy?

Dr Gaia Brezzo:

I think we’ve touched on it already, Fiona. You mentioned diet, of course that’s super important; exercise, again, good for the heart and also very good for the brain. And I think what’s come up recently as well, that I’ve found really interesting and it’s something that I’ve never really thought of, is contact sport. So how that affects your brain health and also impacts your vasculature. So if we’re thinking about like rugby, even football, which is obviously a lot less, you’d say, impact, compared to rugby, but just head butting the ball does make a very huge damage to the brain. And the thing I really liked is that because then that research was funded, we understood what happened, and this actually shaped and changed some of the rules within both of those sports, which ultimately benefits public health, which is really what we want to do. So yeah.

Dr Fiona McLean:

I think that’s really interesting about the sport. I do think it’s interesting because that research has had a lot of support actually from the officials in the game as well. But I guess what you’ve got to ask, maybe it’s a bit of a controversial question is, if it comes out as these studies build, if it comes out that these sports do actually cause a lot of damage to the brain and leads to dementia and later life illness, what then do these professional bodies do about that? Because they’ve said… I think football, for example, said up to a certain age, they shouldn’t be heading the ball. But then does that mean when they become professional footballers, do they then either not the skill to head the ball, or they don’t know how to head it safely? What do they really do? Do they take that aspect out of football completely? Would that ever happen, or do you think the pushback of sort of, “But that’s the game, and that’s the culture of the game,” would be too much for them to make those big changes? [Crosstalk 00:56:35].

Dr Sophie Quick:

I suppose in any sport, you could argue, just to, again be controversial. I suppose in any sports, they’re putting their bodies at risk in other ways. They’re putting other parts in danger by doing any athletics or any sports. So is it then just considered a potential risk of being a professional rugby player or something? I wouldn’t agree with that myself, but perhaps that would be something that would be thought of.

Dr Fiona McLean:

So, I think the person that we should ask on this is Josie, because this used to be your area of research.

Dr Josie Fullerton:

Yeah, so that’s right. So my first post-doctoral role was, as I mentioned, the Glasgow TBI Archive. And-

Dr Fiona McLean:

So TBI, just to be clear, is?

Dr Josie Fullerton:

Sorry, just to be clear, it’s Traumatic Brain Injury.

Dr Fiona McLean:

Traumatic Brain Injury.

Dr Josie Fullerton:

So I worked at the TBI archived, Traumatic Brain Injury up at the Queen Elizabeth Hospital. And I am a horse rider, and I know that coming off a horse, you will bang your head. And I probably have got concussed more than all three of you put together. In horse riding, you can wear a helmet, it won’t protect you against concussion. And I know and knew what I was getting into. And the benefits for me, personally, outweigh the risk. I am a much happier person when I go horse riding. So my mental health is much better. My physical health is much better. And I would personally say, for me, I know that it is a risk, but I still take it. Like Sophie mentioned, you could still fall off and break your leg. [Inaudible 00:58:14], hasn’t happened yet.

Dr Josie Fullerton:

But it is a risk that we’re all willing to take. And I think it’s more difficult when it comes to parents and children, because it’s the parent making the decision for the child. A parent knows if it gets on a bike, it might get knocked off. And I think as long as the parents are informed, and we as scientists keep researching this area… And yes we can limit heading and tackling. But I do think there is a part of it that we just have to accept that you will become injured in sport, physically, either your brain or a limb.

Dr Fiona McLean:

So I guess, what we’re saying as well is, it any different to anything else that might be a bad thing for your brain health? So eating unhealthy, we have to give those choices to individuals, about whether they choose to eat lots of chocolate or high fat or high salt foods. So I guess maybe this, you’re saying it’s the same thing, like we have to give people the choice of whether they want to play sports, where they might get injuries, whether it be to limb or their brain? And that’s part [crosstalk 00:59:26].

Dr Josie Fullerton:

Don’t get me wrong. I think-

Dr Fiona McLean:

Living is [crosstalk 00:59:28].

Dr Josie Fullerton:

Yeah, exactly. And I think they’re doing the right things. Through rugby, we’re doing, if in doubt, sit out. There are things we’re putting into place to avoid secondary brain injury, which is a totally different thing. So I totally agree with that.

Dr Fiona McLean:

How is secondary brain different?

Dr Josie Fullerton:

It’s different in that if it could occur again, it could be as bad as death, essentially. So obviously, I have stepped away from TBI research. So I’m not the most up-to-date in my knowledge, but-

Dr Fiona McLean:

You’re the most up-to-date here though.

Dr Josie Fullerton:

I’ll say it here, on this podcast right now. So it’s different in the way that it’s a different pathology. It’s, you have a single TBI, you get assessed, you sit out. But if you’re not getting assessed and you’re getting straight back on, and you’re getting a second knock to the head, that could be fatal, but could be much, much more severe than if you had just set out, you were assessed. And then it was… The other thing is, as it comes down to there, is an outright test for concussion. There is a blood test that you can do where you can get a biomarker measured in your bloodstream that says, “Yes, this person is concussed. You cannot go back on that pitch.” I do think risk is a huge thing. But exercise is such a big thing in brain health. So I think it’s…

Dr Fiona McLean:

It’s about weighing it out.

Dr Josie Fullerton:

… it’s a fine balance, yeah.

Dr Fiona McLean:

Yeah. Well, I think what you’ve said there about sort of primary and secondary injury, that shows how it’s so important to have that kind of moment where you stop, if you are injured. And yeah, I guess it comes back into education and giving people the information, so they can make their own choice about their own lives.

Dr Josie Fullerton:

One more thing. So we were, sorry, discussing about lifestyle choices. So Gaia mentioned diet and exercise. Two other things I thought of was rest. I think rest is so important in brain health, especially when you think of our current work-life balance after COVID. A lot of us are working at home. A lot of us don’t maybe have the best work-life balance that we maybe did before going in. So I think resting… And when we rest, it’s when our brain processes things, stores things. And I think it’s so important to try and have a bit of rest down time. I listen to a podcast… Sorry, alternative podcast available. And listen to a podcast recently. And it reckoned that an adult should be resting for 42% of the 24 hours. And so they get… But that’s the limit.

Dr Fiona McLean:

You can’t see on the podcast, but all of our faces read, “What? Like I don’t any of us are doing that.”

Dr Josie Fullerton:

No.

Dr Sophie Quick:

Is that resting or sleeping?

Dr Josie Fullerton:

Both, including rest, sleep, doing exercise, something outside of like the severe mental intense activity.

Dr Fiona McLean:

So I think yeah, Sophie, you’ve kind of touched on this about sleep, right?

Dr Sophie Quick:

Yeah. Because I was thinking you were meaning sleep, which of course is really important. For brain health, that’s really crucial. I know that there’s a completely different set of things that happen when you’re sleeping in the brain. But yes, a rest is also clustered, it’s just not work, I suppose then.

Dr Josie Fullerton:

Yeah.

Dr Sophie Quick:

Okay.

Dr Josie Fullerton:

Just downtime.

Dr Sophie Quick:

Downtime.

Dr Josie Fullerton:

Also, either meditating, yoga, just reflecting and taking a pause. And I think especially with the scientists, we’re probably not very good at doing that.

Dr Fiona McLean:

Yeah, potentially. I think sleep’s an interesting to touch on as well, because there’s a lot of studies showing that during sleep, there’s sort of a big flush out of waste products out of your brain. And there’s some really interesting research around Alzheimer’s and amyloid buildup, and how actually sleep might be really important to prevent that by washing out anything that could build up in the brain. But this is interesting. So we need to rest and sleep. That’s good to know. I feel this is justifies when I sit on the couch and like binge watch.

Dr Josie Fullerton:

Oh yeah, yeah. Totally.

Dr Sophie Quick:

My brain needs some brain health.

Dr Josie Fullerton:

Yes.

Dr Sophie Quick:

It’s for brain health.

Dr Fiona McLean:

It’s brain health.

Dr Josie Fullerton:

That’s why I said I watch Married at First Sight, Australia is because I’m going to shut down mood.

Dr Gaia Brezzo:

Oh my God, let’s not start this. It’s not going to end.

Dr Sophie Quick:

So we should be watching something very casual. We should be watching something very casual. We shouldn’t be watching anything too straining. So just something very cool, very calm, brings us joy. So I can re-watch my favorite movies over and over and over again, and it’s for brain health.

Dr Josie Fullerton:

Totally.

Dr Sophie Quick:

Right?

Dr Josie Fullerton:

Yeah, totally.

Dr Sophie Quick:

Great. Perfect.

Dr Fiona McLean:

Yeah. Yeah. Yeah. Another sort of lead on from that is, talking about other things that are supposed to be good for your brain. And I guess, do any of you know if these other things are also good for your vasculature in particular? So for example, reading. Is reading like… Because they’d say it’s good to, like people who read a lot and do puzzles. That’s really good for preventing declining cognition. But is there any evidence that this is linked to good brain vasculature as well?

Dr Sophie Quick:

I would love to do that study. That’s a brilliant study.

Dr Fiona McLean:

Right, Sophie? We need to write a grant.

Dr Sophie Quick:

Or just maybe just participate in it, that would also be fun.

Dr Fiona McLean:

Or just participate in.

Dr Sophie Quick:

But yeah.

Dr Fiona McLean:

I think that would be interesting to look at blood flow, and see is it… Because you would think that if you’re doing something that does sort of stretch your brain, but in a sort of nice way, so not the stress that we’re talking about, but yeah puzzles or something, in my mind, it would make sense that there was an increase of blood flow to areas of the brain that would be required for that, and that would maybe be good thing because you’re almost exercising your brain blood vessels.

Dr Sophie Quick:

Yeah, I guess we don’t know whether blood flow, increased blood flow is always necessarily a good thing. Because if you have say a weakened vessel, you could be putting undue stress on a vessel. But maybe it strengthens them. I think it’s possibly context-dependent. But yeah, I don’t know whether we know that blood flow is always a good thing. But we do know that exercise, which does increase blood flow, will exercise, increasing blood flow. We know the exercise is good. It’s good for brain health. I think I read somewhere that like the exercise through antioxidants, can actually help the cells of the vessels as well, I think, which kind of makes sense. So yeah maybe blood flow is always a good thing. I’m not sure.

Dr Fiona McLean:

I think you’re right. I think… To be continued. Do you know what, there’s definitely a paper on this somewhere. But yeah. Yeah, I do know that from my studies, when we look at blood flow, it definitely is decreased in the models I look at, which are obesity type two diabetes. It’s blood flows is decreased in the brain in those models. So that’s not a good thing. But I think when you have a big physical condition, like say if you’ve got quite severe type two diabetes, reading a book is probably not going to offset that. You definitely need… It’s a combination again. We’re talking about this before. It’s a combination of physical health and mental health. And they come together. And if you have both those things, then you’re sort of doing the best you can for your brain.

Dr Sophie Quick:

I guess we just, still have a lot to learn.

Dr Fiona McLean:

Yeah. We do have a lot to learn. And hopefully learning also looks after our brains. So, it’s very circular. So one last question to end on, and we’ve kind of talked about it already, but I’d just love to know this. So we’ve been talking, me and Sophie have kind of declared our love for endothelial cells. So, I guess this is kind of aimed at Gaia and Josie, but what is your favorite brain cell and why? So me and Sophie love endothelial cells because I love them; because I think they’re underrated. I love how they shuttle things back and forward, across the brain, into the brain, out of the brain. That just feels like they’re a very useful cell. And I love this idea that they’re at the interface of everything. So they’re facing the blood, dealing with what’s in the blood, and then they’re also talking to you, and looking after the rest of the brain cells. So that’s why I love endothelial cells. Sophie, why do you love endothelial cells?

Dr Sophie Quick:

Yes, I do love endothelial cells. They’re very good. I think for the same reasons that you said, I think they’re just overlooked. They’re just getting on with the job, they’re really just getting on with everything that they need to do. Although like I said, I do think that when something goes wrong with an endothelial cell, it goes really wrong. So quite like that, they’re a little bit dramatic as well. That’s quite fun. I probably have a soft spot for a microglia. I just think they’re a little bit wacky; microglia, they’re just dashing around, they’ve got things to do. They’re over here, they’re over there, they’re very mobile. I think that’s a lot of fun. But yeah, my heart lies with the endothelial cell, kind of literally, I suppose.

Dr Fiona McLean:

So maybe, I was going to say your heart lies with endothelial cells, and your brain lies with the microglia?

Dr Sophie Quick:

Maybe. My more whimsical side goes for a microglia, because they just seem a little bit wacky.

Dr Fiona McLean:

Gaia, what’s your favorite type of brain cell, and why?

Dr Gaia Brezzo:

Ooh, it’s always been a tricky one for me. So, I’ve started off very vascular. So I was always intrigued by like extracellular matrix, basement membrane and endothelial cells. I do love a good endothelial cell, because I was always interested in how… Oh yeah, how I found my tribe; how like the smallest change to something like blood flow, can impact the brain so differently. And that’s kind of really what got me fascinated about neuroscience, and forms a lot of my background training. But now, I’ve recently joined a very microglia-focused lab. So I’m really starting to appreciate these cells a lot more, and especially quote unquote, “they’ve always been the finesse, the resident immune cell of the brain.”

Dr Gaia Brezzo:

But there’s more and more research emerging, that these cells actually do a lot more than just your cleanup. So actually, there’s a lot of work going on about how they actually control and help modulate the vasculature, and narrow vascular responses. So I think that’s the real sweet spot for me. Vasculature and cell work together is what I aspire. In any cell, that’s what I want. So yeah, I quite like understanding the whole. So that’s why I quite like the neurovascular system, and understanding how-

Dr Fiona McLean:

You’re going quite broad. You’re just like as long as it’s linked with vasculature, you love it.

Dr Gaia Brezzo:

Yeah, pretty much. Even astrocytes, I’m like, “Yeah, I love me a bit of astrocytes,” and just very pan-neurovascular [crosstalk 01:10:19].

Dr Fiona McLean:

Josie, what about you?

Dr Josie Fullerton:

I have to say, this is the geekiest conversation that I’ve had; what’s your favorite brain cell? I love it. I love it. I’m more exciting with Gaia, in that I’m more appreciative of all brain cells. But, I’m going to go a bit rogue and say that my favorite particle is a brain derived extracellular vesicle. [Crosstalk 01:10:51]. What! Just coming at you.

Dr Fiona McLean:

Do you know, I’d just like to say this out loud, but we are in a neuroscience podcast, and nobody said neuron.

Dr Sophie Quick:

Yeah.

Dr Josie Fullerton:

That’s it. Neurons are overrated.

Dr Sophie Quick:

Oh.

Dr Gaia Brezzo:

Yeah, I agree.

Dr Fiona McLean:

Listen, we’re about to lose all our followers for the Dementia Researcher Podcast. Neurons are beautiful to look at though.

Dr Sophie Quick:

They’re very much [crosstalk 01:11:22].

Dr Josie Fullerton:

They are beautiful.

Dr Fiona McLean:

They are very beautiful.

Dr Josie Fullerton:

And if you had said favorite brain region, I would’ve said the cerebellum, because it looks so beautiful when it’s histologically stain.

Dr Sophie Quick:

Absolutely.

Dr Josie Fullerton:

It looks stunning.

Dr Fiona McLean:

I know. Oh, let’s not go down that route too. The hippocampus is also quite beautiful.

Dr Josie Fullerton:

Favorite [inaudible 01:11:38].

Dr Fiona McLean:

But again, I feel… Favorite brain region. Oh my gosh. I don’t know how to pull this back now. So, now that we know everyone’s favorite brain cell, I could talk about brain vasculature health and the blood-brain barrier are all day. But we must bring this Dementia Researcher Podcast to a close. So thank you so much to Gaia, Sophie and Josie for joining me today. We have profiles of all our guests on the website, which includes details of their Twitter accounts. So if you have any questions or you just want to reach out and say hello, then you can drop us a line.

Dr Fiona McLean:

If you take away anything about looking after your brain vasculature from this episode, it should be that we need to eat well, and exercise. And also, as we learned today, rest. Not just sleep, but actually just rest. And these things are not just important for your body, but your brain too. If you’d like to know more, you should also check out the Food for Thought shows from Dr. Sam Moxon, all here in your favorite podcast app, YouTube, and of course on the Dementia Researcher website. Thank you for joining us today.

Voice Over:

Brought to you by dementiaresearcher.nihr.ac.uk. In association with Alzheimer’s Research UK, and Alzheimer’s Society. Supporting early career dementia researchers across the world.

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