Research Projects

The Thoresen Group’s work is translational, taking experimental results into clinical practice. We focus on

  1. Hypoxic ischemic (HI) injury of the term infant around the time of birth (perinatal asphyxia) and effective treatment to reduce brain injury. Such treatments are therapeutic hypothermia, breathing the inert gas xenon as well longer term interventions to improve outcome.
  2. The consequences of intraventricular haemorrrhage (IVH) in the premature infant leading to expansion of the cerebral ventricles (hydrocephalus).

Recurring abbreviations

  • HT: Therapeutic Hypothermia (also referred to as “cooling”)
  • HI: Hypoxia ischemia
  • HIE: Hypoxic ischemic encephalopathy
  • Xe: Xenon
  • XeHT: Xenon (ventilation) combined with hypothermia as a treatment
  • IVH: Intraventricular haemorrhage
  • PHVD: Posthaemorrhagic ventricular dilatation

We pursue this work in two mains settings:

Experimental – Develop models (tissue and whole animal) that mimic the clinical question asked, in order to:

  • understand mechanisms of hypoxic-ischemic injury and repair (36, 40, 50, 54, 59, 59, 100, 146)
  • define the effective time window of therapeutic hypothermia; how late can you start (78, 108)
  • define the ideal degree of therapeutic hypothermia (see abstract)
  • define the ideal duration of therapeutic hypothermia (147)
  • develop interventions for effective neuro- and organ protection
    • Hypothermia (HT); short and long term survival (Neuroprotection: 55, 60, 68, 69, 78, 81, 147; Organ protection: 40, 58, 83, 108)
    • Hypothermia and Xenon (XeHT); short and long term survival (93, 103, 104, 113, 130, 139)
  • investigate interaction with treatment and other morbidities like infection (158, 183) and hyperoxia (141, 185)
  • document potential adverse effects and negative interactions of hypothermia and Xenon with physiology (69, 155)
  • develop a rat model for IVH leading to PHVD after short (79, 85) or long term (133) survival
  • Apply the rat PHVD model in the investigation of drug treatment against PHVD (86, 109, 135)
  • develop a newborn pig model of IVH leading to PHVD after short (101) or long term (187)
  • Apply the pig PHVD model in the investigation of pressure changes after IVH and PHVD (134)

Clinical – Apply the optimal treatment to patients based on fully explored experimental work:

  • Pilot feasibility- and safety studies (for HT: 64, 143)(for XeHT: 163)
  • Phase II randomised controlled trials(CoolXenon2, CoolXenon3)
  • Phase III randomised controlled trials (for HT: 87, 120)
  • Undertake long term follow-up for Phase III randomized controlled trials (140, 168)
  • Undertake further HT trial analysis (91, 92, 94, 99, 102, 106, 114, 121, 122, 136, 137, 144)
  • Feasibility study of premature infants with PHVD undergoing drainage of the ventricular system (80, 98, 148)

Most current projects

  • CoolXenon 2 and 3 randomised trials of XeHT – Between 2010 and 2012, we undertook a single site clinical feasibility study of XeHT – the CoolXenon2 randomised pilot study of XeHT versus HT. We are currently recruiting patients for its continuation – CoolXenon3 – a randomised Phase 2 trial where Xenon treatment is added to standard cooling therapy within five hours after birth.
  • Added therapies to cooling: Xenon inhalation and other interventions
  • Treatment options for severe perinatal encephalopathy when hypothermia is not effective
  • Cooling the right patients with tailored treatment
  • Cooling and infection (158, 183)
  • Cooling and hyperoxia (141, 185)
  • Clinical Xenon delivery devices (117, 179)
  • Audit clinical effectiveness of therapeutic hypothermia in different geographical regions

References
Numbers listed in parentheses refer to publications on the given subject matter, as listed in Marianne Thoresens’ publication list.