What does neurovascular mean?
It refers to the interactions between the nervous system and the vascular system. In the body, we have the nervous system, with the brain, the spinal cord and the various nerves that control movement and receive sensory signals. And we have the blood vascular system, which transports oxygen- and nutrient-charged blood to the various organs and tissues for their survival.
These two systems may appear independent, but on closer inspection, there are significant similarities, particularly in terms of their location. For example, at given points in the body, vessels are aligned with nerves. We can therefore examine their molecular communication : how are molecules exchanged between the two systems, and how do they influence each other, particularly at the start of an individual's growth ?
Neurovascular biology also considers pathological contexts: the role of blood vessels in cerebral diseases, or conversely the role of nerves in cardiac disorders.
In my laboratory, everyone has a project in one of these areas and their various applications.
Why did you choose biology ?
Ever since I was a little girl, I've been fascinated by the human body and how it works. My father worked in a publishing company and often brought me books. One in particular, which explained a little about all the things that go on in our bodies, made a big impression on me. At the time, I knew nothing about research. My goal was to become a doctor, and naturally I decided to study medicine.
After the baccalauréat, I did a first year... and quickly realized that it wasn't what I'd imagined ! There was a lot of rote learning in a short space of time and a very competitive spirit, which didn't suit me. Unsurprisingly, I didn't pass the entrance exam for the second year. However, I quickly picked myself up and reoriented myself towards a biology degree, initially with a view to returning to medicine via a "passerelle".
Once I was at university, I realized that it suited me better: instead of memorizing " ", I took the time to understand. That's what originally appealed to me about biology : understanding living things.
So you no longer wanted to become a doctor of medicine ?
At the end of my degree, I was still wondering whether I should go on to study medicine. As part of a subject on career guidance, I had to interview a person to illustrate a scientific profession. I had chosen " chargé de recherche ", which is, let's say, the classic tenure-track position, and I interviewed a neuroscience researcher. She really impressed me with her passion for the job.
I then asked her for an observation period, which she accepted. I was an apprentice researcher for two months, navigating between scientific questions and experiments to prove hypotheses. It was a revelation. I decided to pursue a Master's degree in neuroscience and then a PhD at the Collège de France, in the team of Dr. Isabelle Brunet - my thesis supervisor.
It's quite funny, because when I was young I thought I wanted to treat people, but in reality it was curiosity that guided me. Being a doctor might have frustrated me.
Your thesis was on intranervous vascularization : what is it ?
As the name suggests, it represents the blood vessels inside peripheral nerves. A peripheral nerve is a kind of cable that connects the brain and spinal cord to the rest of the body.
When I arrived in Isabelle Brunet's laboratory, initially for my Master's internship 2, the project had just got off the ground. It was a brand-new project, and my task was to scour the literature and produce the first results.
The first axis was to study how the vessels inside nerves come into being during embryonic development. In fact, quite a few researchers had identified the mechanisms by which blood vessels or brain vessels are formed, but there was virtually no data in the literature on the subject of vessels in nerves.
I therefore characterized the successive stages of this intranervous vascularization, at the embryonic stage, using an experimental model of the sciatic nerve. This is the longest nerve in the body, starting at the bottom of the spine in the lumbar region and running down the leg.
What did you find ?
In an embryo fifteen days after fertilization, the sciatic nerve has no vascularization. Only one day later, a few small vessels enter. These don't come from nowhere : from existing vessels, new branches form, like in a tree, as soon as the body needs more vascularization - when an organ grows, for example.
At the same time, I identified the nerve cells that guide and regulate this vascularization. This is how it always works : some cells produce molecules that attract vessels, while others repel them, resulting in a precise vascular network adapted to the organ's needs.
Fluorescence microscope image of a nerve. In blue, axons (neurons) ; in red, endothelial cells (blood vessels). sonia Taïb
The second axis of your thesis deals with neurovascular interactions in pathological contexts..
My team was interested in chemically-induced peripheral neuropathy. To break down : " neuropathy " means a disease that affects the nervous system ; " peripheral " because it's the peripheral nerves that are impacted ; and " chemically induced ", because this pathology is a side effect of a chemical molecule. In this case, a drug called oxaliplatin, used in chemotherapy against colorectal cancer.
It's an effective treatment, but unfortunately in over 80 % of cases, patients develop neuropathy. The latter leads to disabling symptoms : hypersensitivity to cold and touch. Simply taking an object from the fridge causes abnormal pain. Often, the only solution is to reduce or stop cancer therapy altogether. There is no real treatment for this neuropathy, either preventive or curative.
That's where we started. Oxaliplatin is administered intravenously, and then exerts toxicity on the neurons present in the nerves. We asked ourselves : how does this molecule travel from blood vessels to neurons, and what role does intranervous vascularization play in the context of chemically-induced peripheral neuropathies ? Promising results are in the pipeline..
Where are you now ?
Since graduating, I've been continuing my research at the Collège de France in order to finalize the publication of my work, and to support the PhD student who is taking over from me on the question of oxaliplatin-induced neuropathy.
As far as my thesis is concerned, I think I've been rather lucky. Experimental science is difficult on principle, but my environment made the ordeals easier to overcome. Thanks to my supervisor, I was able to speak at quite a few congresses, including prestigious international ones, right from my first year, which is not something everyone gets to do. On these occasions, I even received a few awards. It was very motivating !
My plan now is to do a post-doctorate in Toronto, to complete my training in vascular biology. A career in the public sector is becoming increasingly complicated, but I'd like to stay in academia and, eventually, why not become a lecturer, as I'm very interested in teaching. During my PhD, I had the opportunity to give basic biology lectures to L1 psychology students. I really enjoyed the experience, although it was stressful. Passing on knowledge is really important and satisfying.
----------
Dr Sonia Taïb works at CIRB, in the Molecular Control of Neurovascular Development team headed by Dr Isabelle Brunet.
Photos © Patrick Imbert
Interview by Océane Alouda