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Newborns are not tiny adults

Blogger: Eva Brekke Foto: Merethe Wagelund/NTNU Info

One of the mantras from our training in paediatrics was that “children are not small adults”. By this they meant to remind us that we cannot make a direct transfer of what we know about diagnostics and treatment of adults to children, and assume it will be successful.

Our findings show how important it is to do research on different age groups, also within basic research. What works in adults could be potentially harmful in children and newborns, and what does not work in adults could turn out to be a valuable therapy.

This is something I that have experienced through my research, where we have looked at how the brain of seven days old rats work after an episode of blood and oxygen deprivation, also known as hypoxic-ischaemic (HI) brain damage.

HI brain damage during pregnancy or birth is one of the causes of cerebral palsy (CP). We found that the newborn brain cells work very differently from what we know about adult rat brains.

baby2istock

Oxidative stress is one of the mechanisms that damage brain cells when there is a lack of blood and oxygen. A process called the pentose phosphate pathway [1] plays an important role in the defence against oxidative stress by producing substances that are used to renew the body’s own antioxidants. Due to this, the antioxidants can be used again and again to neutralise oxygen radicals.

This could make the newborn brain especially vulnerable to oxidative stress.

In adults the activity of the pentose phosphate pathway increases during oxidative stress [2,3], which probably acts as a defence mechanism in the adult brain. To our surprise, we found that in newborns, however, the activity of the pentose phosphate pathway is reduced after an episode of blood and oxygen deprivation. This could make the newborn brain especially vulnerable to oxidative stress.

Another mechanism that damages the brain cells when there is a lack of blood and oxygen in the brain, is uncontrolled firing of the neurons which releases large quantities of the signalling substance glutamate. Such uncontrolled firing occurs when the neurons have too little energy, and is therefore common during HI when the lack of nutrients and oxygen causes an energy-crisis.

Glutamate in large quantities is poisonous to the brain cells. In adults the formation of glutamate is reduced during and after and HI episode [4,5]. In newborns the production is also reduced in the phase after HI, but with one important difference: Compared with other processes, the production of glutamate is actually prioritised over for example energy-production! This could be a contributing factor to the brain cells not being able to optimise the energy levels, with the result that this new glutamate is released and damages the surrounding brain cells.

Both oxidative stress and high doses of glutamate can lead to cell death even after the cells have regained sufficient blood supply. This means that brain cells are still being damaged at a stage when it may be possible to offer treatment. It is believed that much of the damage in the newborn brain happens after the blood supply has been restored. If we could give effective treatment at this stage, much of this damage could possibly be avoided.

These are two examples of how the brain seems to function differently in newborn and adult rats.

These are two examples of how the brain seems to function differently in newborn and adult rats. If the same differences exist between newborn and adult humans, this could lead us onto new ways of treating newborns that have experienced episodes of too little blood or oxygen to the brain during a difficult pregnancy or a complicated birth.

Our findings show how important it is to do research on different age groups, also within basic research. What works in adults could be potentially harmful in children and newborns, and what does not work in adults could turn out to be a valuable therapy.

This blog post is based on the paper “The Pentose Phosphate Pathway and Pyruvate Carboxylation after Neonatal Hypoxic-Ischemic Brain Injury”, which was recently published in the Journal of Cerebral Blood Flow and Metabolism: http://www.nature.com/jcbfm/journal/vaop/ncurrent/full/jcbfm20148a.html

Links:

[1] The Pentose Phosphate Pathway: http://en.wikipedia.org/wiki/Pentose_phosphate_pathway

[2] Bartnik BL, J Neurotrauma 2005: http://www.ncbi.nlm.nih.gov/pubmed/16238483

[3] Domańska-Janik K., Resuscitation 1988: http://www.ncbi.nlm.nih.gov/pubmed/2839885

[4] Håberg A, Neurochem Int 2006: http://www.ncbi.nlm.nih.gov/pubmed/16504342

[5] Håberg A, JCBFM 2001: http://www.ncbi.nlm.nih.gov/pubmed/11740207

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Filed under Child and youth, Neurological, NTNUmedicine, Research

Time spent in bed, in a sitting position and on physical activity early after stroke

Blogger: Torunn Askim Torunn Askim

 

 

 

 

Early on a Friday morning in the middle of November, PhD student Anne Hokstad and I, headed towards Trondheim airport, Værnes, to catch the early flight to Copenhagen. We did not spend much time in bed that night as the airport taxi came at 4.20 am. However, there should be good opportunities for sleeping over the next 24 hours, although it had to be in a sitting position, either at Kastrup airport, or during the 13-hour flight to Singapore.

Sleeping in a sitting position on economy class is not easy, and we arrived for a stop-over in Singapore early Saturday morning after only two hours of interrupted sleep. It was tempting to take a short morning nap, but we decided to spend the day on walking along the streets of Singapore, and keep going throughout the day instead. After a good night sleep, in bed, we were ready for some more physical activity the next morning until the departure of our flight to Melbourne, Australia. Again we spent Sunday night in a sitting position on a plane with a few hours of interrupted sleep, again we arrived early in the morning, and again we spent the next day being active, settling in in Melbourne.

The purpose of this exhausting flight was to visit Associate Professor Julie Bernhardt and her colleagues at the Stroke Division at Florey Institutes of Neuroscience and Mental Health in Melbourne, Australia, and to continue our research collaboration on physical activity early after stroke.

So, why all this interest in time spent in bed, in sitting position and on physical activity? It is well known within the stroke society that acute treatment in a comprehensive stroke unit saves lives and reduces disability. Furthermore, from the stroke unit trial in Trondheim we know that early mobilisation and activity is the most significant factor for beneficial outcome, followed by stabilising diastolic blood pressure. It is therefore of great interest and importance to have a closer look at the activity levels offered to stroke patients admitted to stroke units across the world, and furthermore to analyse its association to outcome. 

Physical activity can be measured in different ways, both by observation and by use of body worn sensor systems. Julie Bernhardt has developed the Behavioural Mapping method which is a standard method of observation every 10-minute from 8 am to 5 pm over the course of a single day. At each observation, the patient’s location, who the patient interacts with, and which activity the patient is doing, is registered. Up to 10 patients can be observed at a time. At the Department of Neuroscience at NTNU, we have observed more than 500 patients, including a pilot study of 117 patients from the stroke unit at St. Olavs Hospital and a multisite study of 411 stroke patients admitted to 11 Norwegian stroke units, mainly in Central Norway but also in Bærum, Lillehammer and Tromsø. All behavioural mapping forms completed in these studies have been scanned and sent to Florey for processing and the initial analyses.

The primary aim of our visit this time was to help cleaning up the data and to bring a complete and tidy overview over the activity levels of the patients back home again. In the pilot study we found that an increased proportion of time spent in bed in the early phase after stroke was strongly associated with an increased risk of poor outcome (death or disability) three months later. While, to our surprise time spent on physical activity, like standing, walking and climbing the stairs, did not show the inverse association.

We are now very interested in the results from the 411 patients included in the Life Early After STroke – the LEAST study. Will the results from the pilot study be confirmed? And, will the activity levels provided by the 11 Norwegian hospitals differ significantly? That is what PhD student Anne Hokstad is going to figure out over the next 18 months.

We did not spend very much time in bed during our Melbourne trip. However, a great proportion of the time was spent in a sitting position, either at work at Florey, on the train to Heidelberg, on the plane to Alice springs, or on the 17-hour bus tour from Alice Springs to visit Ayers Rock (or Uluru as the Aboriginals call it) during the weekend in-between.

As we both are aware of the risk of spending too much time in sitting position, we tried to spend a significant proportion of the time also on physical activity like running on the treadmill at the hotel, walking along the Yarra River and also by walking along the streets of Melbourne.

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Filed under Neurological, NTNUmedicine, Research, Stroke

From different angles

Survival is for many brain tumours related to how much of the tumour is removed during surgery. The methods and technology developed in Trondheim facilitates more complete resection of brain tumours, while preserving normal functionality. For low grade gliomas it has been shown that early radical resection with intraoperative 3D ultrasound results in better survival, than using a watchful wait-and-see approach [1]. Importantly this survival benefit can be achieved with low morbidity, preserving normal function and long-term quality of life in most instances. Image-guided surgery with the aid of intraoperative 3D ultrasound, as used in Trondheim, is therefore a useful tool for achieving safe and effective brain tumour surgery.

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Filed under Cancer, Neurological, NTNUmedicine, Research

Edvard and May-Britt Moser in The New York Times

Read Professor Edvard and May-Britt Moser interview in The New York Times.

NYT

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Ask a Researcher: Computational neuroscience and neuroinformatics

MedFakNTNU_ProfMennoWitter_

Guest blogger: Professor Menno Witter

 

 

 

Question:

What’s the core difference between “computational neuroscience” and “neuroinformatics” ? Are they used interchangeably ?

Answer:

Neuroinformatics stands for the meeting between neuroscience and informationscience and it includes a number of different approaches to hjerne2understanding the brain including to a large extent what is defined by computational neuroscience.

Computational neuroscience aims to give quantitative descriptions of functionally and biologically realistic neurons/neuronal networks and to capture those in realistic models that can be used to phrase new hypotheses to be experimentally tested. This field is also often loosely referred to as computational modeling within a neuroscience context.

Neuroinformatics in addition comprises the development of tools and databases to manage and share the overwhelming amount of neuroscientific data, as well as the development of tools to analyze these data. The latter includes tools for complex multidimensional analyses of electrophysiological data or the complex statistics needed to analyze functional imaging data. The website of the International Neuroinfromatics Coordinating Facility (INCF) is a good resource for more information. www. incf.org

This was first featured on our website 19.04.2010

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