The aim of a collaboration between researchers in Denmark and the USA is to glean new knowledge about the many different types of neurons that make the human brain work. It could have implications for the design of drugs for conditions such as dementia and for rehabilitation of patients after a stroke. The project is receiving funding from the Lundbeck Foundation.
Can you ask someone about to undergo surgery for a brain tumour to donate living brain cells to science? The answer is yes.
And within a few months, cells left over from brain tumour surgeries performed by neurosurgeons at Aarhus University Hospital will begin to play a key role in efforts to map neurons in the human cerebral cortex.
Basically, in time, this mapping should enable neuroscience to eliminate the need to use mice and other rodents as laboratory animals when attempting to answer questions about neurons in the human cerebral cortex. This is the part of our brain that is crucial to cognitive skills such as learning and abstract thinking.
‘There are countless questions of this kind,’ says Professor Marco Capogna from the Department of Biomedicine at Aarhus University.
‘For instance, how many different types of neurons do we have in the cerebral cortex? We don’t have the answer today – maybe 50? Maybe more? Other questions, which are just as important to answer, concern how the various cells communicate with each other. And we need to know as much as possible about this if we’re to try to design drugs for dementia and other brain disorders.’
Marco Capogna – who holds degrees in experimental psychology, biology and neuroscience – is heading the mapping study, and he has just been awarded a research grant worth DKK 3.5 million by the Lundbeck Foundation.
He will work with Jonathan Ting, a neuroscientist at the Allen Institute for Brain Science in Seattle, USA, to acquire new knowledge about neurons in the cerebral cortex, using studies of living human brain cells.
Ting has developed a technique that registers activity between neurons at molecular level, and Professor Capogna will use the equipment for his analyses of the living brain cells he receives from the neurosurgeons at Aarhus University Hospital.
There are many contexts in which scientists benefit from using mice, rats and other mammals in studies whose ultimate aim is to develop new drugs or therapies for humans. Human beings actually have many basic biological mechanisms in common with other mammals.
However, when it comes to the brain, things get a lot more complicated – because our brains can do much more than the brains of other mammals. This is why we are interested in studying the way the human brain works by looking at living human brain cells. On the other hand, it creates an ethical dilemma:
How do we do this? For obvious reasons, we can’t simply insert registration devices into the brains of our trial subjects.
This is where the neurosurgeons from Aarhus University Hospital, headed by Professor Jens Christian Hedemann Sørensen, come in. When they remove a brain tumour from a patient – cutting through the cerebral cortex – some of the tumour is always ‘left over’. These are cortical cells which are removed before closing and suturing.
The two professors began working together a few years ago to study these cells, with the permission of the Danish Research Ethics Committee and the individual patient.
When the neurosurgeons at Aarhus University Hospital perform surgery on a brain tumour, Marco Capogna is often waiting outside the door of the operating theatre. He receives the left-over cortical tissue, which is collected in a small container and submerged in oxygenated fluid with added nutrients and salts.
Twenty minutes later, Professor Capogna is back at the Department of Biomedicine. He can keep the cortical tissue alive for some hours while he studies the neurons in the tissue. But first, he cuts the tissue into slices approximately 0.3 mm thick.
Marco Capogna explains that previous studies have dealt with issues other than mapping of human cortical cells and their communication networks, which will soon begin due to the funding provided by the Lundbeck Foundation:
‘The difference is that we now have access to the special analysis equipment developed by Jonathan Ting. On top of that, the American research team has recently proven that human brain cells can be kept alive in the laboratory for up to a few weeks if they are kept in the right fluid. This technique gives us a whole range of new options for studying neurons in the cerebral cortex.’
During the difficult conversation
Jens Christian Hedemann Sørensen explains that cancer patients are extremely generous when it comes to donating their cells to science:
‘It may not seem an easy task to put this difficult question to someone in severe crisis because they’re about to have a brain tumour removed. But neurosurgeons are used to these difficult conversations, and none of the 25 or so patients we’ve asked so far have said no. That’s impressive. We’re deeply grateful, and we’re convinced that patients will also give us permission to use these cells for research in the future.’
However, Jens Christian Hedemann Sørensen explains that the next phase of the study – mapping of neurons and their communication networks within the cerebral cortex, which will start up in a few months – requires extended permission from the Research Ethics Committee:
‘In order to keep these cells alive for several weeks, they need to be stored – cultivated – in cerebrospinal fluid. Human beings produce around half a litre of this fluid every 24 hours, and it flushes through our brain and spinal cord. We need to ask the Research Ethics Committee for permission to use the surplus cerebrospinal fluid to cultivate the cells and cerebral cortex removed during brain tumour surgery. I’m in the process of writing the application.’
The surplus cerebrospinal fluid the researchers need to cultivate cortical cells can come from patients admitted to the intensive care unit, for example after a traffic accident or a stroke. As Jens Christian Hedemann Sørensen says, some of these patients need to have cerebrospinal fluid drawn off regularly to prevent it from accumulating in the brain:
‘Today, we destroy the cerebrospinal fluid we draw off. In the future, we’d like permission to use some of this for cultivation of cells. This will require permission from the patient, and I’m sure we’ll get this when we explain that it will support important research – for example, how we best facilitate rehabilitation after a stroke by electrical stimulation of the patient’s cerebral cortex.’
‘In such cases, we really need to know how the different types of cell in the cerebral cortex work together – and Professor Capogna’s analyses will help elucidate this.’
Marco Capogna’s grant comes from the LF & NIH BRAIN Initiative. This is a collaboration between the Lundbeck Foundation and American research giant National Institutes of Health (NIH). The collaboration enables neuroscientists at Danish scientific institutions to enter into research partnerships with colleagues in the USA.