Searching for the Missing Link in Preterm Brain Injury

Dr Thorsten Gorba

Research Fellow

Liggins Institute

University of Auckland

Background to Research

Treatment and care of small prematurely born babies, of which there around 500 a year, comes at a high annual cost of $50m.  Approximately 50 of the 500 babies, who weigh less than 1.5kg at birth, die each year.  The surviving babies are highly susceptible to brain injury and subsequently develop problems in establishing the right connections between different brain areas.  About 10% of infants born less than 1500g will exhibit the severe spastic motor deficits of cerebral palsy and more than half will later suffer from less severe motor, cognitive and visual disabilities.

Lack of oxygen supply to the brain and infection are generally considered to be the cause of these injuries but we believe that disruption of normal developmental processes in the brain contribute to the problems later in life.

What are your research objectives?

We are working on the theory that the injury to the immature brain, due to lack of oxygen, may harm signpost and scaffold cells, leading to young, migrating nerve cells becoming disoriented and unable to establish the correct brain structure.  Because these nerve cells have gone astray we believe they will not be able to connect with their right partners in other brain regions, preventing information exchange and processing.  This could contribute to the motor, cognitive and visual problems.  Our research will hopefully provide a better understanding of how brain injury in prematurely delivered babies disrupts their normal brain development.  Out of this we can plan more targeted and effective therapeutic approaches, to give premature babies a better chance in life, and hopefully reduce costs to the health system.

How will you conduct your research?

Our group has established an infant rat model of the brain injury caused by lack of sufficient oxygen supply in preterm babies, which has been validated and repeatedly published in scientific journals.  The laboratory based research will allow us to ask new questions about the pathology and explore therapeutic interventions in a faster and more cost effective way.

Are there others in your field in NZ or globally conducting similar research?

No other group in New Zealand uses the same animal model.  It is used by another group in Geneva, Switzerland, who are our collaborators.  The Department of Physiology at the University of Auckland is successfully using a foetal sheep model to study the effects of reduced oxygen supply, but is not researching the same hypotheses as we are.

What is innovative about the approach you are taking?

If we can confirm our theory it will help with the development of appropriate therapeutic approaches to prevent or limit preterm brain injuries.

Our study which involves a combination of the infant rat injury model with living brain organ culture techniques is a powerful new approach, which will literally open a window, to study disruption to preterm infant brain development as it happens, rather than retrospectively.

The protective and restorative therapeutic approaches we will be testing in the lab are novel and our team, which is working closely at the clinical interface, is committed to seeing our research translate to positive hospital treatment for these premature babies.

If you achieve your objectives what will that mean to those suffering from the disease or to the knowledge advancement of this disease?

Our recent clinical monitoring studies suggest that it is possible to detect injuries to the brain of preterm babies during the first day, providing an opportunity to apply neuroprotective and restorative therapies which we hope to discover and verify with our laboratory work.  This will have obvious beneficial spinoffs for newborn premature babies and their families.

Is there national or international collaboration on your research project?

Nationally we collaborate with Dr Malcolm Battin (Paediatrics, School of Medicine, University of Auckland).  We have international collaborations with Dr Stephane Sizonenko (Child Development Unit, Department of Paediatrics, School of Medicine, University of Geneva), Professor Terrie Inder (Malinckrodt Institute of Radiology, Washington University Medical Centre, St Louis, USA) and Dr Vince Russo (Endocrine Research, Murdoch Children’s Research Institute, Parkville, Victoria, Australia).  These collaborations will allow us to explore therapeutic strategies and to relate our research to clinical data.