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Professor Marianne Thoresen Neuroprotection and the newborn brain Full contact details |
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Projects - Diseases - Processes - Techniques - Equipment - Funding - Collaborations - Teaching - Group members - Publications & further information
Research
Worldwide, newborn infants suffer death or permanent brain damage caused by diseases arising before or around the time of birth. We do translational research aimed at developing effective treatment:
- We have developed three experimental models that mimic important diseases leading to permanent handicap in children. We use these models to
- understand the mechanism of disease and repair processes
- develop effective treatment against injury caused by lack of oxygen (asphyxia) or reduced brain blood flow
- We have shown that hypothermia is neuroprotecive
- We have shown that adding Xenon to hypothermia doubles the neurorpotection
- We carry out clinical pilot safety and feasibility trials in order to embark on randomised trials
- We fund, plan, carry out and participate in large international trials of hypothermia after perinatal asphyxia that has confirmed the effectiveness seen in our experimental studies
- We are currently implementing neuroprotective hypothermia as standard care in newborn infants both locally and worldwide
We were the first to experimentally demonstrate the protective effect of hypothermia on the newborn brain after HIE and describe mechanisms of hypothermic neuroprotection such as lower cerebral excitatory amino acid concentrations and reduced apoptosis. Left untreated, moderate or severe HIE results in 70% of the infants either dying or surviving with severe disability.
Our hypothermia research successfully translated into clinical trials, and we are now implementing cooling after HIE as treatment for newborn infants around the world.
Since hypothermia reduces injury by, on average, 35%, we are now developing combination therapy to improve its effectiveness.
Adding the inert gas xenon to hypothermia increases neuroprotection to 70% in the rodent model. With our large HIE model we have examined the protective effect of XeHT on brain and organ injury. Since Xenon is very expensive we have developed a unique delivery system for Xenon (uses < 0.5L gas per hour) necessary for effective delivery in a clinical setting. We plan to translate this combination therapy to allow its medical use.
In premature infants hydrocephalus following intraventricular haemorrage is a condition for which there is no effective treatment. Seventy percent of these children develop cerebral palsy and or cognitive delay.
We have developed the first long term survival neonatal models of this condition.
We are currently testing whether draining out the blood or giving antifibrotic drugs inhibit the processes that disrupts the reabsorption of cerebrospinal fluid with the aim to cure the condition.
- The neuroprotective effect of Xenon inhalation and hypothermia in both a small and large neonatal survival model
- Defining what time window, Xe concentration, duration of inhalation and delay of treatment limit the effectiveness of XeHT
- The effect of xenon hypothermia on organ protection (heart, lung, liver, kidney)
- Clinical use of Xenon, feasibility study
- Protective strategies against posthaemorrhagic ventricular dilatation and white matter injury after intraventricular haemorrhage in both a small and a large model with long term survival
- A series of physiological and neuropathological studies related to these projects, in particular cerebral autoregulation, bloodflow studies, EEG changes and detailed examinations of the brain.
Further investigations into neuroprotection of both the term and preterm brain, and of the paediatric and adult brain after cardiac arrest and stroke.
Ischemic brain damage from many causes and ages; perinatal asphyxia, cardiac arrest, perinatal and adult stroke, cerebral palsy, cognitive disability, intraventricular haemorrhage in premature infants, hydrocephalus and seizures
Neuroprotection in a wider sense, white and grey matter injury, cellular markers of brain injury, excitotoxicity, long term survival, behavioural and neuromotor examinations
Cardiovascular monitoring, laser Doppler flow studies, Intracranial pressure, regional temperature, EEG, aEEG, neurological assessment, long term behavioural testing, ultrasound imaging, biochemistry, immuno-histochemistry, light microscopy, histology
Cardiovascular and intracranial pressure monitoring equipment, EEG, temperature, cerebral blood flow velocity, ultrasound imaging, O2, CO2, and metabolic markers
Projects - Diseases - Processes - Techniques - Equipment - Funding - Collaborations - Teaching - Group members - Publications & further information
Grants and funding
- SPARKS
- Laerdal Foundation for Acute Medicine (Norway)
- Action Medical Research
- BBSRC
- MRC (clinical projects)
- Swedish MRC
Collaborations
In Bristol:
- Professor Seth Love - Neuropathology, Frenchay Hospital
- Professor Elek Molnar - MRC Centre for Synaptic Plasticity, University of Bristol
- Professor Andrew Whitelaw - Neonatology, Southmead Hospital
External collaborators:
External collaborators:
- Professor Linda deVries - Utrecht, The Netherlands
- Professor Donna Ferriero - San Francisco, US
- Professor Pierre Gressens - Paris, France
- Professor Alistair Gunn - Auckland NZ
- Professor Henrik Hagberg - Gothenburg/London
- Dr Mathias Karlsson - Karlstad/Stockholm Sweden
- Helen Porter - Perinatal Pathology, Leicester, UK
- Professor Mary Rutherford - Imperial, London UK
Teaching
Undergraduate and postgraduate teaching in Neonatology. Physiology
Running Postgraduate courses x 3/year (CPD approved) - see details of courses for more information.
Publications, recommended reading and further information
Recent selected publications:
Thoresen M, Hobbs C, Wood T, Chakkarapani E, Dingley J.
Cooling combined with immediate or delayed Xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia.
J Cereb Blood Flow Metab 2009 (1-8) E-pub Jan 14
Malcolm R. Battin, Marianne Thoresen, Elizabeth Robinson, Richard A. Polin, A. David Edwards, Alistair Jan Gunn, on behalf of the Cool Cap Trial Group.
Does head cooling with mild systemic hypothermia affect requirement for blood pressure support?
Pediatrics 2009 Mar;123(3):1031-6
Liu X, Borooah M, Stone J, Chakkarapani E, Thoresen M.
The effect of 3-day therapeutic hypothermia on serum gentamicin levels in new born encephalopathic infants.
Pediatrics 2009 (in press)
Chakkarapani E, Thoresen M, Hobbs C, Aquilina K, Liu X, Dingley J.
A closed-circuit neonatal xenon delivery system: technical neuroprotection feasibility study in newborn pigs.
Anesthesia & Analgesia 2009 (in press)
For more general background reading:
Thoresen M, Whitelaw A. (2005)
Therapeutic hypothermia for hypoxic-ischaemic encephalopathy in the newborn infant: review.
Current Opinion in Neurology April 2005;18(2):111-116. (Review)
Erecinsca M, Thoresen M, Silver IA (2003)
Brain metabolism and hypothermia.
Journal of Cerebral Blood Flow and Metabolism 23:513-530
Thoresen M (2000)
Cooling the newborn after asphyxia - physiological and experimental background and its clinical use.
In: Protecting the Perinatal Brain (Ed) Thoresen M - Seminars in Neonatology 5: 61-74
Please also see the article 'Keeping a Cool Head', on pages 4-5 in the special Neuroscience edition of Re:search, at www.bris.ac.uk/neuroscience/extfiles/re-search_pdf/.
Please also find more about Marianne Thoresen's research and career with her CV.
Projects - Diseases - Processes - Techniques - Equipment - Funding - Collaborations - Teaching - Group members - Publications & further information