Welcome to EANcast, your weekly source for education, research and updates from the European Academy of Neurology.

Welcome everyone to this new episode of our podcast.

Today, I'm very delighted to have as my guest professor, Natalie Nassau.

She is a professor of neurology and drug physician of the University of Poitiers in France.

She is also the chair of the Education Committee of the EAN and she's also co-chair of the Scientific Panel of Neurosonology.

research mainly focuses on cerebral circulation and the impact of the autonomic nervous system, but I would like Natalie to introduce herself, please.

Well, hi everyone and thank you, Roberta, for this very kind introduction.

It's my pleasure to be here with you.

So my name is Nathalie Nass, what I do, well, I'm a stroke physician and for my research, mainly focused on, as Roberta said, the regulation of cerebral blood flow, how this is modified by the autonomic nervous system and also cardiovascular stress in a more general way and how this impact from the autonomic nervous system will and modify the prognosis of those acute brain lesions as in stroke or TBI and how it can also have an impact on accelerated cerebral vascular aging.

And one of my main interests is actually how extreme physiology can help us understand what happens.

in pathological conditions and one of the extreme physiology situations to study is space or microgravity in general and this is a very nice input for us on what happens in actually both healthy aging and also pathological conditions.

So I'm very interested about what you said about space, but let's begin from the start.

How does someone even get in the field of research of cerebral circulation in space?

How did you start working in this field?

It's one thing that goes to very long time ago.

My interest in space, how human bodies can adapt to space.

to this extreme environment with radiations, with bouncing temperatures, then how could one human being adapt to that?

That is a very wonderful thing.

I've been interested in it since very, very long time, even before I started medical studies.

And when I was a resident in your Rolci resident in Toulouse University Hospital, I had the opportunity to prepare parallel to my neurological studies.

The university diploma from Toulouse University, I was very lucky to have Professor Anne-Paville Lautrand as a tutor, as a mentor.

She is a renowned researcher in space studies and actually I did my research memoir for this university diploma on cerebral blood flow regulation.

in microgravity.

So this is how it started, and it's still going on with the discoloration with Professor Anperli Lautramot and Dr.

Marc Carmelville to study sugar blood flow regulation in microgravity conditions.

Yeah, this is ongoing.

So when people imagine studies on astronauts, they often picture experiments on international space station.

but in practice how are these studies really conducted?

I guess you conduct some studies on Earth I imagine.

so what are the models that you're using.

Well actually as you know when astronauts go astronauts, cosmonauts, spationauts, whatever you want to call them, when they go into space, whether it's near or far, where they don't have.

They don't have lots of things that they can carry with them.

Space is very limited.

And this is how actually everything that could be portable, everything that was easy to take there was used.

And this is how we got very easily the studies of cerebral blood flow from the Transparenial Doppler monitoring.

This was done many times, and then to be able to have more data from a larger number of individuals, then we performed the microgravity simulation studies that are based on two main models, either head down bed rest, minus six degrees, until the whole body for many weeks, until twelve weeks.

Or dry immersion, that means that the volunteers are in a swimming pool with their skin protected from the hypothermia by a plastic film and they can stay there for several days.

And this is a very hard, quick mimic of microgravity condition always.

So we don't say, we don't say there's no gravity, it's absolutely no gravity.

It's not possible, there will be no gravity.

But that's a microgravity.

Well, this sounds like an ideal job to be laying in a pool for some days, as you use LTE volunteers, I guess, for these studies, right?

Oh yeah, we have very enthusiastic volunteers and I had the chance of talking to them and to see how, why they are there, at least the French ones who are to do the space clinic.

And actually, you have mainly two categories for my experience, either the people who are in the health business like us, or people who have a long interest in space.

So engineers who work in companies had to do the space or...

having or their students in this field.

So, yeah, that's often a strong intellectual interest for them to come and say, hey, I'm volunteer.

So, and let's talk about what actually happens in the brain in space.

Can you explain us how cerebral hemodynamics change in microgravity?

Well, the most categorical thing is a fluid shift towards the upper body.

and this can go to one point five liters or two liters of fluid that is shifted toward the upper body and this gives this characteristic puffy face.

Okay, people remember from the photo of the Spassionaut.

And not only that, actually, the fact that people are up there, they're not doing, they don't have the exercise to do.

And also they do not solicitate their muscles against cavity.

So these three factors are the major importance in bringing and modifications of the cardiovascular system.

And what happens is that actually the body interprets this fluid shift as actually if they were in excess or fluid, because the receptors for our blood volumes are in the upper part of the body.

And then what happens?

The Neuroindulgrin system...

Everything will work as if this were an excess, and the consequence is hypovolemia as a reaction to this.

And this is how we find that actually in microgravity, human being can easily have until ten to fifteen percent less of blood value.

And this will have consequences once astronauts come back.

to us because actually to adapt again to microgravity in this condition is difficult.

And this is of a particular actually concern if they have to do a maneuver after landing to get quickly out of the spacecraft.

So this has been for a long time my motive for studies and concern.

How does autostatic intolerance happen?

How are we able to counter that?

And actually syncopely will come from diminished cerebral confusion.

And this is how our interest is focused on the cerebral blood flow regulation.

And not only for that, also because of timeological consequences, because mainly due to this fluid shift, the intracranial pressure will increase.

And as a consequence of this, the ocular pressure will increase.

And sometimes we can observe edema.

and actually papillary edema.

And this can have also consequences on the ability to see correctly.

Okay, this is reversible phase, but still it's a matter of preoccupation.

And so the changes in the fluid, in the intracranial fluid, both from blood pressure changes, both from the autostatic intolerance and its consequences on cerebral perfusion and also from increased ICD and papillary edema, these are the main concerns in terms of what we take care of as a neurologist.

So you said that these changes are reversible, is that correct?

And how long does it take for these changes to reverse?

To be variable from one individual to another, But even when they are asymptomatic modifications in terms of a papillary edema, for instance, this is preoccupying, because if we think that we will send a human being to Mars, for instance, we need to have a sort of anticipation of what could be done to limit these consequences.

knowing that there will be an entire individual variability that we observe already.

So when astronauts come back from space, do they have kind of an intermediate gravity to re-adapt or do they just go back to their, let's say, normal life?

So the idea is that through this rigorous exercise program is to limit the shift that we observe of the autonomic nervous system going towards more and more stress reaction.

And how do we do that?

Well, actually like we do in our patients who have been for a long time in a bed-ridden position and who have a little bit of trouble gaining their cardiovascular ability capacity to do exercise again.

So the idea of the exercise is to limit this impairment of the cardiovascular adaptability.

And at the center of the autonomic nervous system, there is one parameter we measure.

It's the baroeflex.

It's the restopia of feedback mechanism, mainly based on the vagal mechanisms of adapting the heart rate to the changes of blood pressure.

And this has been for a long time been studied in microgravity.

And this is actually the one parameter that goes down very quickly.

both in space and also in microgravity simulation studies.

This is how we expect to limit the state conditioning by the physical exercise.

We know that this will increase the vagal component, the parasympathetic, and limit the stress sympathetic overactivation.

I don't want to go too specialized on this, but we have new data.

also showing us that the increased intracranial pressure by itself will drive sympathetic activation.

And this is also important to explain why there is this shift toward more sympathetic stress, cardiovascular activation in these volunteers or microgravity studies.

So is what affin to the brain in space somehow similar to some pathological conditions?

on earth, can we use it as a model for something?

I don't know.

There has been a preoccupation with actually the mimicking of accelerated aging.

Of course, we know that for bone and muscle, and this is also why the exercise program is important to limit the loss of bone and muscle, but also for arterial stiffness, for instance, there are studies showing some increase in arterial stiffness, what comes to large arteries, and we do not have data yet, prospective data for the microvascular cerebral system, but because of this shift.

away from vegan and towards sympathetic activation in space.

Because we have similar data in patients, young patients who have sickle cell disease, for instance, having this premature aging that is associated with this shift away from vegan and towards sympathetic activation.

There is a hypothesis that could be if we do not have countermeasures that are applied rigorously and they are sufficient.

it could be a model of premature aging and the data we have right now come from artery stiffness.

But we do not have evidence to say it's irreversible and we are still actually stunning the impact of the countermeasures of limiting these changes and also shortening the reversal of these changes.

So, and beyond the changes in circulation and this adaptation that say are mostly reversible, do we know about any changes in brain structure or function, either during the missions, but maybe also afterwards or in the models that you're using for study this condition?

There are also these cerebral vascular changes we know about mainly because actually of the deconditioning from gravity and when we stun them and we want to see changes of parameters what we see is that auto-regulation means the capacity of the cerebral blood flow to adapt to changes in blood pressure.

is modified in the dispassionates and in microgravity studies volunteers.

And actually this is variable.

at the beginning we thought this would be uniformly actually modified in these in these valentine.

This is variable and actually the main concrete in there is again the autonomic nervous system.

And if we study the cerebrovascular system independently from the cardiovascular autonomic nervous system, we don't have a clue what's happening.

Partly due to these brain studies, we showed actually that the homeostatic mechanisms of the bowel reflex at cartobascular level and the cerebral auto-regulation at cereobascular level are interacting all the time.

And that this impact of the total nervous system of auto-regulation is huge.

So this is for functional changes.

When it comes to structural changes, now we are writing us again to this discussion about the stiffness of the arteries and we mainly have the data that come from the Ecopythe studies knowing that astronauts can carry their probe and the angle can be modified from an operator who is on the ground.

And from these studies that have been performed in microgravity conditions, well, there is data about stiffness of a modification of structure, probably, but you know my answer is for that, probably driven also by the sympathetic activation that brings...

vasoconstriction and the system.

and then second step is as you point to potential structural changes.

Because we do not know yet actually from the biological point of view what is behind this tuning stiffness.

Thank you very much and I do have a curiosity.

so nowadays space travel is no longer only for astronauts when we're starting to talk about space tourism and we know that while astronauts are super well selected they're super healthy and they undergo a lot of checks before their missions.

It doesn't seem like space tourism is so, the selection is so strict.

So I was wondering, from your perspective, are there some important risks for brain and cerebral circulation in people that are spending, of course, shorter periods in space for tourism, and they're not trained astronauts?

I would say that it is safe to go to space when the people are not really trained to go to space.

We are not within the selection that was there before, like at least when military pilots know that we are super fit.

becoming a little more diverse profiles of people going to space, but still there is training, countermeasures, there are risks, we talk about them, so at this stage I will be really cautious about this and thank you for bringing up the question.

So I guess that space is not really a walk in the park, isn't it?

No.

Thank you very much for your answers and I'm sure our audience is very interested.

Is there something else you think we should add?

Well, I think that we have benefited, we had lots of benefits coming from these space studies which encourage us to develop a thorough understanding of how cerebral blood flow regulation works and this is really precious.

Who asked me, Rodis, dealing with cerebral circulation regulation, so we are in depth with the strokes, so I want to do the space studies for that.

Great.

Thank you very much, Nathalie, for being a guest in our podcast.

This was a very fascinating conversation.

And thank you very much for making a topic that is very complex and very far from the usual topic, so clear and so engaging.

This has been EANcast Weekly Neurology.

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