Prof Mario Valentino

Showcasing Brains

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In the second part of the final installment in the series dedicated to brain-related research, neuroscientist Professor Giuseppe Di Giovanni explains the inspiration behind the Malta Neuroscience Network and how it is helping to bring brain-related research to the forefront.

“The human brain is the most complex organ in the known universe. This complexity makes it the last and hardest frontier in medical research, and unravelling the brain’s secrets could change the lives of millions of people of all ages who suffer from neurological and psychological conditions, lesions or addictions.” Professor Giuseppe Di Giovanni

It was a warm afternoon in September 2014 when Professor Giuseppe Di Giovanni first realised that while there were many people interested and working in neuroscience, very few of them communicated between one another. This epiphany came as he was thinking about the Studio 7-produced RIDT and Science and the City documentary, Jien Min Jien, which outlined the research that was taking place at the University of Malta at the time. Professor Di Giovanni was one of those involved in the project, and organised the part about how neuroscience research had grown over the previous 10 years.

As a neuroscientist himself, Professor Di Giovanni has been working on understanding the pathophysiology of the central monoaminergic systems of different neuropsychiatric disorders (which, in layman’s terms, means the way diseases, such as depression, Parkinson’s and Alzehimer’s, affect the brain) for over 20 years. That, as well as his work attracting funding from many international bodies, such as ERUK UK, Physiological Society UK, PON Italy, and various national Maltese bodies (including the MCST R&I 2013 Grant), made him the ideal candidate for it and for what was to come.

“Malta is a small country, therefore collaborations among scientists is of pivotal importance for the scientific development of the nation and the education of our students,” he says. “So I went to Professor Richard Muscat’s [former pro-rector for Research & Innovation at the UoM] office and I said to him, ‘Richard, what if we form a virtual neuroscience institute to bring together all of the neuroscience researchers in Malta?’

“I could see the enthusiasm on his face. In fact, he immediately said ‘Yes’,” he continues. “After that, I started contacting everyone working on neuroscience, and anyone who I thought would be enthusiastic about this proposal to create a network of people, all with different neuroscience specialisms.” Among those people to first support the Malta Neuroscience Network (MNN) was Wilfred Kenely, the CEO of RIDT.

Working together, Professor Di Giovanni and Wilfred Kenely worked on holding the first Malta Brain Awareness Week (BAW), and fundraising which was meant for Professor Di Giovanni’s research on depression and epilepsy, was channeled to the entire research community. That funding will now, after being peer-reviewed, fund the first two projects.

“BAW is the global campaign that aims to increase public awareness of the progress and benefits of brain research,” says Professor Di Giovanni. “This global celebration, launched by The Dana Alliance for Brain Initiatives, presents an opportunity to bring attention to advances in brain science and advocate for science funding.  The best part is that activities are limited only by the organisers’ imaginations and include open days at neuroscience labs, exhibitions about the brain, lectures on brain-related topics, social media campaigns, displays at libraries and community centers, and classroom workshops, among others.” But that is just the tip of the iceberg of what the MNN network was set up to do.

The Network aims to encourage and facilitate interdisciplinary research so as to bring together academic members from all the Faculties of the UoM with an interest in the rapidly-growing field of Neuroscience, as well as to promote interdisciplinary dialogue among all those involved in neuroscience.

“But we also want it to go further,” he explains. “The MNN’s role is also to foster research and training in neuroscience at UoM; to sponsor and coordinate seminars by leading neuroscientists from home and abroad; to offer study units in neuroscience that may be included in both undergraduate and postgraduate programmes; to collaborate with local and overseas centres, universities, programmes and individuals with similar purpose and scope; and, just as importantly, to raise public awareness in neuroscience, brain disorders, and mental health through public talks, evening courses, and an annual Brain Awareness Week.”

Although it is still in its infancy, the Network has already been accepted as the 43rd member of the European Neuroscience Societies by FENS – “A pivotal affiliation in the development of neuroscience in Malta,” he says. And it is also collaborating with the Mediterranean Neuroscience Society (of which Professor Di Giovanni is the treasurer).

“The Mediterranean Neuroscience Society was created to support and help strengthen all initiatives that bring together Mediterranean neuroscientists. This has been achieved through schools and biannual meetings that have proven to be highly beneficial, not only for the scientific exchanges, but also in terms of training opportunities for students and young researchers. I am very happy that, after a successful 2015 meeting in Cagliari (Sardinia, Italy), the next meeting will take place in Malta in 2017, with the MNN being involved in its organisation,” he explains.

Rizzolatti Di Giovanni
Prof Rizzolatti & Prof Di Giovanni

Along with Professor Di Giovanni, the MNN is made up of numerous other members, including Professor Helen Grech, Dr George Azzopardi and Professor Mario Valentino, whose research we covered over the past few months. Moreover, Professor Giacomo Rizzolatti, who discovered mirror neurons, and Professor Vincenzo Crunelli from Cardiff University, who is a world-renowned neuroscientist specialising in epilepsy, are also part of the network.

The importance of such a Network cannot be overestimated, however. Going back to the initial quote by Professor Di Giovanni, the brain is our most precious tool – be it for health, problem solving, or the advancement of technology and society. Yet, although many would agree with this, few take the time to truly acknowledge the importance of research related to the brain.

The MNN is now changing that, bringing to the fore the people and the research that is taking place on our island and connecting them to many international channels. And while there is no doubt that there is still a long way to go before the brain becomes a priority – a statement that beggars belief in itself – Professor Di Giovanni (along with the MNN) are definitely on the right track.

You too can be part of this fascinating world of research by supporting researchers in all the faculties of the University of Malta. Please click here for more information on how to donate to research through the Research Trust (RIDT). To join the Malta Neuroscience Network Programme, please fill in this brief online membership application.



The Link Between White Matter & Stroke

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In the third installment dedicated to research in Brain related areas, we chat to Professor Mario Valentino about the Laboratory for the Study of Neurological Disorders’s latest finds, and about how these are ushering in a new era in real-time visualisation of the dynamics in stroke onset for the treatment of strokes.

Mario ValentinoIn 2012, the European Society of Cardiology and the European Heart Network released statistics that placed stroke at number two on the list of the single most common causes of death in Europe. In fact, some 1,100,000 people die from it annually on our continent alone.

But what is a stroke exactly?

“The brain is the most complex system in the universe consisting of 100 billion neurons which are interconnected in a still mysterious way,” explains Professor Mario Valentino, who, upon his return to Malta from stints at the Max Planck Institute for Neurological Research in Germany, and the Department for Neurology at Washington University and the Hope Centre for Neurological Disorders in the USA, set up the Laboratory for the Study of Neurological Disorders here at the University of Malta.

“Electrical signals coursing through this awesome network somehow underlie our perception of the world and our actions within it,” he continues. “Because of all this, the brain is an energy-hungry organ, and despite comprising of only 2% of the body’s weight, the brain consumes more than 20% of our daily energy intake.

When the blood supply to the brain is interrupted or blocked for any reason, the consequences are usually dramatic. Control over movement, perception, speech, and other mental or bodily functions can be impaired, and consciousness itself may be lost. Deterioration continues over hours, or even days, and depends primarily on the severity and the duration of the ischaemia [inadequate blood supply to the brain].

“Despite major advances in prevention and rehabilitation, few neurological injuries are as debilitating as stroke. The disease is currently the third leading cause of death after heart disease and cancer and the leading cause of long-term disability worldwide; it is similarly devastating in Malta.”

What’s worse is that, the already-staggering numbers are expected to grow in the years to
come. This is mostly due to the enhanced susceptibility to stroke at an older age as a result of an increase in life expectancy.

“The magnitude of the problem on pre-term babies is equally extraordinary and the main cause of cerebral palsy, the most common neurological disorder of infancy,” Professor Valentino adds. “Unfortunately, current options for acute treatment are extremely limited and there is an urgent need for new treatment strategies. After all, fast and timely restoration of blood flow is imperative for recovery after a stroke.”

Over the last few years, Professor Valentino, along with the members of the Laboratory for the Study of Neurological Disorders, has been working on understanding how white matterstroke.4722529_std (matter found in the brain that actively affects the way the brain learns and functions) could actually play a part in strokes.

“Stroke was once considered a disorder of blood vessels, yet growing evidence has led to the realisation that the biological processes underlying stroke are driven by the interaction of neurons, glia [supporting cells of the nervous system], vascular cells and matrix components, which actively participate in the mechanisms of tissue injury and repair,” he says.

“That’s why we have to understand how the injuries are occurring if we are to prevent them from happening, and that’s what driving us to study cell-to-cell interactions in the normal and diseased nervous system.”

For five years, the team has sought to understand not just the properties of individual cells, but also the dynamics of the loss of their interactions during a stroke. To do this, they have set-up a powerful technique for in vivo (occurring in a living organism) imaging that is centred around two-photon microscopy (a fluorescent imaging system that combines the use of a pulsed infra-red laser) that allows them to visualize in real-time the cellular workings of the brain.

“The mastering of two-photon microscopy combined with the use of mouse models whose different cell populations shine in different colors allow for simultaneous multicolor imaging, as well as unlimited number of examinations of the same field of view through a small ‘window’ in the skull. This opens the way to quantitative and correlative analysis of cell distributions and interactions in a truly physiological environment.

“In addition, large amounts of data are collected from a single animal, hence allowing for a reduction in the number of animals engaged in an experimental study and improving the significance of the results.”

As part of this study, Professor Valentino and his team have recently shown that the vulnerability of white matter to stroke varies during development, and that the metabolism of the brain’s wiring revolves around lactate that is provided by Brain_Cortex_Harvardastrocytes, the main supporting cells in the nervous system.”
It is clear that up to 30% of all strokes in humans occur as infarcts deep in the white matter – so much so, that these are what produce specific stroke impairments, including a weakness on one side of the body and cognitive decline. Moreover, white matter has been linked to many other disorders, including dementia and several leucodystrophies in children.

“While the pathophysiology of grey matter [a main component of the central nervous system] in stroke has been intensively studied, much less attention has been focused on the white matter, which comprises half of the volume of the human brain,” says Professor Valentino. “Most fibers in white matter serve to connect local or contralateral brain areas, and there is growing recognition of the potential neurocognitive consequences of white matter lesions.

“It is important to point out that the basic research in this area has been limited because of the difficulty in establishing an animal model of subcortical white matter stroke and the minimal volume of white matter volume in rodents,” he continues. “Yet, since neuronal death is seen as a consequence of the failure of astrocytes to support the metabolic demand of neurons, we have proposed that new efforts should be designed to protect the integrity of astrocytes as an alternative strategy for neuroprotection.” This perspective is centred around their recent finding that astrocytes are more vulnerable to ischaemic injury than previously thought.

All this, Professor Mario Valentino hopes, will develop better stroke therapies and help scientists, researchers and doctors understand how the brain’s vasculature (vascular system), and its interaction with neurons and glia cells, is altered after a stroke.

“It is this knowledge of the intricate dynamics and cross-talk between neurons, glia and the vasculature that is unraveling what causes these cells to die, and which might one day lead us to understand how they could be made to recover,” Professor Valentino concludes.

In other words, this study currently being undertaken at the University of Malta is trying to understand what goes wrong in the brain before, during and after someone experiences a stroke, in the hope of being able to rectify the short- and long-term consequences it has on the patient’s brain and life. And while we may not know the outcome for another couple of years, it’s definitely a very promising start.

You too can be part of this fascinating world of research by supporting researchers in all the faculties of the University of Malta. Please click here for more information on how to donate to research through the Research Trust (RIDT).