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⚡️ Flashback: in 2018, Jérôme Laurin and Christophe Pellegrino were already in the NeuroMarseille spotlight in this article exposing their research on post-stroke (Cardiovascular Accident) recovery thanks to the injection of a hydrogel that has the capacity to progressively degrade and release pharmacological molecules.
Today, Jérôme Laurin continues to explore the link between pathology, physical exercise physiology and neuroscience, still in this very particular situation: the post-cardiovascular accident. The researcher participated in the Marseille edition of the Brain Week 2021 and explained his research to the public (watch the replay of his presentation!). NeuroMarseille continues the investigation on his research at the crossroads of disciplines through this article! Curious minds, let’s go for a new dose of neuroscience!
Jérôme Laurin is a doctor in human movement sciences and a lecturer at Aix-Marseille University in the Faculty of Science and Techniques of Physical Activities and Sports. After working at the Institut des Sciences du Mouvement Étienne-Jules MAREY (ISM), he continued his research at the Institut de Neurobiologie de la Méditerranée (INMED), within the team "Early activities in the developing brain". His work focuses on the influence of physical exercise on cerebral and muscular plasticity as well as on the recovery from vascular accidents.
Stroke and physical exercise
A stroke here, a stroke there, but what is its real definition?
The Heart and Vascular Research Foundation defines a stroke as a sudden interruption of blood flow to the brain. Strokes are most often caused either by a clot blocking an artery to the brain and thus interrupting blood flow (ischemic stroke) or by a rupture of an artery in the brain (hemorrhagic stroke). Stroke is the leading cause of disability in adults and the third leading cause of death in France. Exploring avenues of recovery for patients who survive this accident is therefore a major public health issue.
The physiological repercussions of a stroke are well known, but the repercussions on the brain of patients are much less studied. The literature shows that sport is a factor in post-stroke recovery, however, there is a lack of reliable evidence on its effects, particularly on the training methods to be used.
The bottom line: exercise is beneficial for stroke recovery, but … what exercise?
What should we recommend to patients? Jérôme Laurin’s work is part of this problem.
What are the effects of exercise on neuroplasticity?
At the neurological level, the researcher looks at the two hemispheres of the brain, the injured hemisphere on the one hand and the non-injured (healthy) hemisphere on the other. With his team, Jérôme Laurin is studying the effect of endurance on the individual’s functional recovery, whether sensory-motor or cognitive. These are the two aspects most affected by a stroke. For example, at the sensory-motor level, we often observe hemiplegia with loss of sensitivity, known as “hemiparetic”.
A hemibody corresponds to one of the two sides of the body (left or right). Hemiparesis is a partial paralysis of one hemibody (often mobility of the limbs but with little muscle strength), while hemiplegia is a more complete paralysis.
Measuring neuroplasticity in humans involves cognitive or blood tests to measure markers of neuroplasticity. However, to be able to fully verify functional recovery (sensorimotor and cognitive), researchers must be able to observe the presence of neurotrophins (proteins essential for the survival and differentiation of neurons during development and involved in neurogenesis) in the different areas of the brain.
The animal model remains the best way to verify this recovery. The team chose the rat as a model because it has the same neurotrophins as humans. Moreover, using an injury protocol (simulating a stroke), the researchers were able to observe the same type of functional losses in animals as in humans.
Focus on the experimental protocol
How is stroke induced in rats?
The lesion is carried out using the MCAO method, which stands for monofilament intraluminal cerebral ischaemic injury. What is this gibberish? Well, let’s talk technique: a filament is introduced into the common carotid artery and pushed along the internal carotid artery: there it obstructs the start of the middle cerebral artery (the artery most affected in case of stroke in humans). MCAO sutures are the raw material for successful stroke modelling in rats, mice and other animals.
Post-injury (post-stroke) experiments
Jérôme Laurin and his team use the same parameters as humans to measure recovery from exercise.
📌 First step: exercise tests
Exercise tests are performed at two days post-surgery on the injured rats as well as on a control population. These tests consist of having the rats run on a treadmill, in the same configuration as in humans. This test makes it possible to measure parameters such as walking speed or Vo2max, the latter being a very important clinical criterion. Indeed, the Volume of Maximum Oxygen (VO2max) is the maximum quantity of oxygen that the body consumes during an intense effort per unit of time. It is an excellent indicator of the subject’s potential performance in endurance events: the higher it is, the better the performance will eventually be.
These tests show the researchers the strong decrease in the animals’ performance following the lesion and make it possible to determine the sports programme to be carried out according to the “threshold limit” defined for each animal.
📌 Definition of the individualised programme
The sports programme carried out by each animal according to its results in the exercise tests will be either of moderate or intense intensity. Running on the treadmill must be done in a controlled manner so as not to endanger the health of the animal, as would be done in the stroke patient. The interest of the programme lies in the fact that sport has naturally beneficial endogenous repercussions, particularly on neuroplasticity: this is known as the “multi-pill” effect.
The information on the performance and endurance of the animals collected in the two weeks after the injury is the most important! This is indeed a period of intense plasticity that will greatly condition recovery in the long term.
Evidence at the cellular level
📌 Studying neurotrophic factors at the cellular level
In order to prove the beneficial effects of sport on the post-stroke brain, Jerome and his team are also conducting studies at the molecular level by studying neurotrophic factors, such as BDNF or VEGF, as well as receptors related to synaptic plasticity. In addition, Jérôme is studying energy markers of aerobic metabolism; in particular mitochondrial markers, a real energy factory that will influence brain plasticity.
His studies so far show a positive correlation between neurogenesis and these energy markers. This correlation is all the stronger if the training sessions are also positive.
For the future, the aim is to combine the results with the famous “miracle gel“, cognitive exercises and physical exercises. Taken separately, each experiment has had beneficial effects on post-injury recovery, but are these effects increased by combining the three methods? Would inhibition be observed?
📌 Combined studies
The study will soon be completed with the injection of a hydrogel containing pharmacological molecules useful for post-injury recovery. But also with cognitive exercises, in particular, spatial memory in the Barnes maze.
Jérôme Laurin explains that physical exercise is essential for recovery but not sufficient. Combining it with other therapeutic acts is very interesting insofar as it can amplify their effects (particularly the effects of cognitive exercises!).
What about humans?
In humans, a determining factor comes into play: motivation!
It is more than essential to work on these post-stroke recovery processes, as this pathology is very frequent – there are 140,000 cases per year in France – and affects both ageing people and infants. But, in addition to finding the most favourable type of physical training, a key point is to find a way to motivate the patient to follow this training. Jérôme Laurin tells us that being interested in physiology is important but that man is a social animal. This social function of sport is a fundamental component in the recovery process, to keep patients motivated to train for long periods of time and sometimes even for the rest of their lives. The role of structures such as the Heart and Health Clubs coordinated by the Federation of Cardiology is to set up actions and sports monitoring to supervise and motivate patients to adopt a healthy lifestyle to maximise the effect of rehabilitation and minimise the risk of a new accident. Combining pleasure with sport: a scientifically proven recipe for rehabilitation!
The public health issue of stroke also raises a challenge in terms of prevention: informing people about the factors that affect the quality of the arteries, such as smoking, alcohol consumption or stress. This pathology should therefore be included in broader actions to fight against addictions, malnutrition or mental health.
To go further
During Neurobinar #7 which took place on April 29 2021, the PhD thesis of Nicolas Hugues, PhD student under the supervision of Jérôme Laurin, was presented to the NeuroMarseille community. Learn more about his research on the impact of different post-ischemic brain endurance programs in young and ageing rats and the effect on the neuroplasticity of combining endurance with an implantable and degradable hydrogel in the brain! The video is online !