Centre for Brain Research


Fetal Physiology

Principal Investigator


Research interests


We are a multidisciplinary systems physiology team, working on key physiological and pathophysiological questions in the fetus and newborn and on translational research. Our current interests are focused on the cerebrovascular and cardiovascular adaptation to asphyxia in utero and the mechanisms and treatment of post-asphyxial encephalopathy.

Fellows

  • Dr Sherly George
  • Dr David Wu

Current research projects


  • Cerebral hypothermia and post asphyxial brain injury in the preterm fetus
  • The role of endogenous growth factors in promoting recovery from preterm brain injury
  • The pathogenesis and treatment of cystic white matter lesions in the preterm brain Role of endogenous inhibitory neurotransmitters after asphyxia
  • The mechanisms of secondary mesenteric and cerebral hypoperfusion.
  • Chronic hypoxia and ECG prediction of fetal compromise during brief repeated asphyxia
  • The mechanisms of sudden infant death and ALTEs in the post back-to-sleep era.

Active research collaborations


National

  • Dr Sherly Tonkin, New Zealand Cot Death Society
  • A/Prof Jenny A Westgate, Dept of O&G, University of Auckland

International

  • Professor Gordon Power, Loma Linda University , CA
  • Professor Erik Heineman, Dept of Surgery, Maastricht , the Netherlands

Facilities / technology platform

Multidisciplinary Research with clinical applications

Commercial / translational activities

Olympic Technology (Seattle , Wa), development of the CoolCap trial.

Educational conferences


  • Nonalcoholic Steatohepatitis in childhood. 9 th Novo Nordisk Paediatric Endocrine Workshop, Auckland , 25 th August, 2000.
  • Causes of perinatal HIE. Clinical audit presentation (with Warwick Smith and Sue Belgrave), Jade Ward, Waitemata Health, 12 th October, 2000.
  • Insulin infusion pumps: results of meta-analysis. 11 th Novo Nordisk Paediatric Endocrine Workshop, Auckland, 2002
  • Management of Precocious puberty. 11 th Novo Nordisk Paediatric Endocrine Workshop, 2002. Communications to Society · The CoolCap Trial, interview with TV one, presented May 6 th, 2004.
  • "The Development of Head Cooling". Health Innovation Award, (Small group category) awarded by Dept of Health and ACC, New Zealand . Video produced to publicize the award (director Gresham Bradley), 2003.
  • "Fetal Adaptation". Interview with Veronika Meduna. Radio New Zealand Eureka Programme. 2nd of August 2002.
  • "Countering brain damage in premature infants". HRC Newsletter, July 2002.
  • Hypothermia and the newborn, presented by Dr Alistair J. Gunn to HM the Queen, on the occasion of the official opening of the Liggins Institute. 26th Feb, 2002
  • Fetal Origins of Adult Disease. Interview with Alan Coukell. Radio New Zealand Eureka Programme. December 2001.
  • "Babies at risk if left in car seats' New Zealand Doctor, 24th May 2000.

Research publications


  • Bennet L, Quaedackers J, Gunn AJ, Rossenrode S, Heineman E. The effect of asphyxia on superior mesenteric artery blood flow in the premature sheep fetus. Journal of Pediatric Surgery. 35(1):34-40, Jan 2000
  • Guan J, Gunn AJ, Sirimanne E, Clark R, Tuffin J, Gunning MI and Gluckman PD. The window of opportunity for neuronal rescue with insulin-like growth factor (IGF)-1 after hypoxia-ischemia (HI) in rats is critically modulated by changes in post-insult temperature. Journal of Cerebral Blood Flow & Metabolism, 20(3):513-519, 2000 Gunn TR, Tonkin SL, Haden W, Davis SL, Gunn AJ. Neonatal micrognathia is associated with smaller upper airways on radiographic measurement. Acta Paediatrica, 89(1):82-87, 2000
  • Gunn TR, Thompson JM, Jackson H, McKnight S, Buckthought G, Gunn AJ. Does early hospital discharge with home support of families with preterm infants affect breastfeeding success? A randomized trial. Acta Paediatrica 89(11):1358-1363, 2000
  • Gunn AJ, Maxwell L, de Haan HH, Bennet L, Williams CE, Gluckman PD, Gunn TR. Delayed hypotension and subendocardial injury after repeated umbilical cord occlusion in near-term fetal lambs. American Journal of Obstetrics & Gynecology. 183(6):1564-72, 2000
  • Quaedackers JS, Beuk RJ, Bennet L, Charlton A, oude Egbtrink MG, Gunn AJ, Heineman E. An evaluation of methods for grading histological injury following ischemia/reperfusion of the small bowel. Transplantation Proceedings, 32(6): 1307-1310, 2000
  • Battin MR, Dezoete JA, Gunn TR, Gluckman PD, Gunn AJ. Neurodevelopmental outcome of infants treated with selective head cooling following perinatal asphyxia. Pediatrics, 107(3):480-484, 2001
  • Bennet L, Oliver MH, Gunn AJ, Hennies M, Breier BH. Recovery from asphyxia in the premature fetal sheep is associated with differential changes in IGF-1 and IGF-2 and their binding proteins. Journal of Physiology( London ), 531(3):835-841, 2001
  • Guan J, Bennet L, Wu DD, George S, Waldvogel HJ, Gluckman PD, Faull RLM, Crosier PS and Gunn AJ. Insulin-like growth factor-1 reduces post-ischemic white matter injury in fetal sheep. Journal of Cerebral Blood Flow and Metabolism, 21(5):493-502, 2001
  • Lumbers ER, Gunn AJ, Zhang DY, Wu JJ, Maxwell L and Bennet L. Non-immune hydrops fetalis and activation of the renin angiotensin system after asphyxia in the mid-gestation fetal sheep. American Journal of Physiology, Regulatory and Integrative Physiology, 280: R1045-1051, 2001
  • Tonkin SL, Gunn AJ. Failure of mouth to mouth resuscitation in cases of sudden infant death. Resuscitation, 48(2), 181-184, 2001
  • Westgate JA, Bennet L, de Haan HH, Gunn AJ: Fetal heart rate overshoot during repeated umbilical cord occlusion in sheep. Obstetrics & Gynecology 97(3):454-459, 2001
  • Westgate J, Bennet L, Brabyn C, Williams CE, Gunn AJ. ST waveform changes during brief repeated asphyxia in near term fetal sheep. American Journal of Obstetrics & Gynecology. 184(4):743-751, 2001
  • Westgate JA and Gunn AJ. Early neonatal mortality and timing of low risk births. Data suggest that difficulties in fetal monitoring are magnified at night. BMJ 322(7283):433-434, 2001
  • Williamson K, Gunn AJ, Johnson N, Milsom SR The impact of ethnicity on the presentation of the polycystic ovarian syndrome. Australian and New Zealand Journal of Obstetrics & Gynaecology. 41(2):202-206, 2001
  • Battin MR, Harding J, Gunn AJ. Neonatal Scleroderma. Journal of Paediatrics and Child Health. 38(5):533-534, 2002.
  • Milsom SR, Gibson G, Buckingham K, and Gunn AJ. Factors associated with ovulation and conception after Clomiphene Therapy in WHO Group II anovulatory women. Australian and New Zealand Journal of Obstetrics & Gynaecology, 42(2):170-175, 2002
  • Tonkin SL, Vogel S, Bennet L, Gunn AJ. Positional upper-airways narrowing and an apparent life-threatening event. New Zealand Medical Journal, 115:24-25 2002.
  • Westgate J, Bennet L, Gunn AJ. Meconium and fetal hypoxia: some experimental observations and clinical relevance. BJOG, 109(10): 1171-1174, 2002
  • Battin MR, Penrice J, Gunn TR, Gunn AJ. Treatment of term infants with head cooling and mild systemic hypothermia (35 and 34.5 OC) following perinatal asphyxia. Pediatrics,111:244-251, 2003
  • Cao Y, Gunn AJ, Bennet L, Wu D, George S, Gluckman, PD, Shao, XM and Guan J. Insulin-like growth factor (IGF) -1 suppresses oligodendrocyte caspase-3 activation and increases glial proliferation after ischemia in near term fetal sheep. Journal of Cerebral Blood Flow & Metabolism, 23(6): 739-747, 2003
  • Hunter CJ, Bennet L, Power GG, Roelfsema V, Blood AB, Quaedackers JS, Guan J, George S, Gunn AJ. Key neuroprotective role for endogenous adenosine A1 receptor activation during asphyxia in the fetal sheep. Stroke, 34(9): 2240-2245., 2003
  • Tonkin SL, McIntosh C, Hadden W, Dakin,C, Rowley S, Gunn AJ. Simple car seat insert to prevent upper airway narrowing in preterm infants: A pilot study. Pediatrics 112(4): 907-913, 2003
  • Milsom SR, Sowter MC, Carter MA, Knox BS, Gunn AJ. LH levels in women with PCOS: have modern assays made them irrelevant? BJOG, 110(8):760-764, 2003
  • Quaedackers JS, Roelfsema V, Hunter CJ, Heineman E, Gunn AJ, Bennet L. Asphyxia leads to polyuria and disturbed renal function in preterm fetal sheep. Am J Physiol Regul Integr Comp Physiol, 286(3):R576-83, 2004
  • Roelfsema V, Bennet L, George S, Wu D, Guan J, Veerman M, Gunn AJ. The window of opportunity for cerebral hypothermia and white matter injury after cerebral ischemia in near-term fetal sheep. Journal of Cerebral Blood Flow and Metabolism, in press, Feb 2004
  • Guan J, Miller OT, Waugh KM, McCarthy DC , Gluckman PD and Gunn AJ. TGF-beta improves somatosensory function after hypoxia-ischemia in adult rats. Neuroreport, 2004 12;15(6):961-964. 2004
  • Quaedackers JS, Roelfsema V, Heineman E, Gunn AJ, Bennet L. The role of the sympathetic nervous system in post-asphyxial intestinal hypoperfusion in the preterm sheep fetus. Journal of Physiology, April 8, 2004 , 10.1113/jphysiol.2004.062554

Reviews and commentary in peer reviewed journals


  • MacLennan A, for the International Cerebral Palsy Task Force, including: Gunn AJ, Bennet L, Westgate JA. A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensus statement. BMJ 319(7216):1054-1059, 1999.
  • Reprinted by permission of the BMJ, Australian & New Zealand Journal of Obstetrics & Gynaecology, 40(1):13-14. Australian Health Law, Australian Midwifery Journal, Recent Advances in Obstetrics & Gynecology [ed John Bonnar], 2000.
  • Gunn AJ. Cerebral hypothermia for prevention of brain injury following perinatal asphyxia. Current Opinion in Pediatrics, 12(2):111-115, 2000.
  • Gunn AJ & Gluckman PD. Should we try to prevent hyperthermia after cardiac arrest? Pediatrics, 106(1):132-133, 2000. Gunn AJ & Battin M. Hypothermic centralization: New use for old knowledge? Pediatrics, 106(1):133-134, June 2000.
  • Gunn AJ. Changing causality of post asphyxial seizures in term infants. Expertos Invitados, Sociedad Iberoamericana de Information Cientifica, http://www.siicsalud.com/dato/dat019/00818046.htm, 23rd August, 2000.
  • Gunn AJ, Gunn TR, Mitchell EA. Is changing the sleep environment enough? Current recommendations for SIDS. Sleep Medicine Reviews, 4(5): 453-469, 2000.
  • Niermeyer S, Kattwinkel J, Van Reempts P, Nadkarni V, Phillips B, Zideman D, Azzopardi D, Berg R, Boyle D, Boyle R, Burchfield D, Carlo W, Chameides L, Denson S, Fallat M, Gerardi M, Gunn A, Hazinski M, Keenan W, Knaebel S, Milner A, Perlman J, Saugstad OD, Schleien C, Solimano A, Speer M, Toce S, Wiswell T, Zaritsky A: International Guidelines for Neonatal Resuscitation: An excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Pediatrics 106(3): E29, 2000.
  • Newly born Panel, [including Gunn AJ]. The international guidelines 2000 for CPR and ECC. A consensus on science. Part 11: neonatal resuscitation. Resuscitation 46(1-3):401-416, 2000.
  • Gunn AJ. Comprehensive followup care and life threatening illnesses among high risk infants [invited commentary]. Evidence-based Healthcare, 5(2):31, 2001.
  • Gluckman PD, Pinal CS and Gunn AJ. Hypoxic-ischemic brain injury in the newborn: pathophysiology and potential strategies for intervention. [Invited Review]. Seminars in Neonatology, 6(2):109-120, 2001.
  • Gunn AJ, Bennet L. Is temperature important in delivery room resuscitation? [Invited review] Seminars in Neonatology, 6(3):241-249, 2001.
  • Gunn AJ, Quaedackers JS, Guan J, Heineman E, Bennet L. The premature fetus: not as defenceless as we thought, but still paradoxically vulnerable? Developmental Neuroscience. 23(3):175-179, 2001.
  • Niermeyer S, Van Reempts P, Kattwinkel J, Wiswell T, Burchfield D, Saugstad OD, Milner A, Knaebel S, Perlman J, Azzopardi D, Gunn A, Boyle R, Toce S, Solimano A: Resuscitation of newborns. Annals of Emergency Medicine 37(4 Pt 2):S110-S125, 2001
  • Feigin VL, Anderson CS, Rodgers A, Anderson NE , Gunn AJ. The emerging role of induced hypothermia in the management of acute stroke. Journal of Clinical Neuroscience, 9(5):502-507, 2002.
  • Gunn AJ, Bennet L. Hypothermia in the management of hypoxic-ischemic encephalopathy. [invited review]. NeoReviews, 3: e116-122, 2002
  • Tonkin SL, Gunn TR, Bennet L, Vogel SA, Gunn AJ. A review of the anatomy of the upper airway in early infancy and its possible relevance to SIDS [invited review]. Early Human Development, 66(2):107-121, 2002.
  • Westgate JA, Bennet L, Gunn AJ. Fetal ECG monitoring. [invited review] Fetal and Neonatal Medicine Reviews, 13:2:119-139, 2002.
  • Bennet L, Gunn AJ. Memories of the fetal heart. [invited commentary]. Am J Physiol Regul Integr Comp Physiol. 285(3):R517-8, 2003.
  • Guan J, Bennet L, Gluckman PD, and Gunn AJ. Insulin-like growth factor-1 and post-ischemic brain injury [invited review]. Progress in Neurobiology, 70(6): 443-462, 2003.
  • Feigin V, Anderson N, Gunn AJ, Rodgers A, Anderson C. The emerging role of therapeutic hypothermia in acute stroke. The Lancet Neurology, 2(9):529, September 2003.
  • Tonkin SL, Bennet L, Gunn AJ. The upper airway in early infancy and SIDS [invited review] Expertos Invitados, Sociedad Iberoamericana de Information Cientifica, http://www.siicsalud.com/des/des036/04225001.htm, 2004.
  • Gunn AJ. Importancia de la vía aérea superior infantil en la patogénesis de algunos eventos potencialmente fatales y de muerte súbita infantil, Sociedad Iberoamericana de Information Cientifica, Feb 27th, 2004.
  • Gunn AJ, Bennet L. Magnesium sulphate given before birth does not significantly reduce death or cerebral palsy in premature babies, but may improve motor dysfunction [invited commentary]. Evidence-based Healthcare, 8(3):162-164, 2004.

Chapters in books


  • Bennet L, Westgate JA, Gluckman PD, Gunn AJ. Pathophysiology of asphyxia. Chapter 23, In: Fetal and Neonatal Neurology and Neurosurgery. 3 rd Edition, M. Levene, M. Whittle, F.A. Chervenak, J. Punt, M.J. Bennett (Eds), Harcourt Brace, London, pp 407-426, 2001.
  • Gunn AJ, Guan J, Bennet L, Jones K, Gluckman P. Hypoxic-ischemic injury of the perinatal brain and neuronal rescue. In: Cerebral hypoxia and ischemia in forensic medicine, Research in Legal Medicine. M. Oehmichen. (Ed), Schmidt-Romhild, Lubeck , Vol 24, pp41-57, 2001.
  • Gunn AJ, Gluckman PD, Bennet L. Asphyxia and the developing brain. Chapter 4. In: Acquired Damage to the Developing Brain; Timing and Causation. W.M.V. Squier (Ed). Arnold , London . pp 56-76, 2002.
  • Westgate JA, Bennet L, Gunn AJ. Intrapartum hypoxia. In: Birth asphyxia and the brain: basic science and clinical implications. SM Donn , SK Sinha, ML Chiswick (Eds), Futura Publishing Co, NY. Chapter 11, p243-278, 2002.
  • Bennet L, Westgate J, Gluckman PD, Gunn AJ. Fetal responses to asphyxia. In: Fetal and Neonatal Brain Injury: Mechanisms, Management, and the Risks of Practice, 2 nd Ed, Stevenson DK and Sunshine P (Eds), Cambridge University Press, Cambridge, UK. Chapter 4, pp 83-110 2003.
  • Gunn AJ, Guan J, Bennet L. Neuroprotective mechanisms after asphyxia. In: Fetal and Neonatal Brain Injury: Mechanisms, Management, and the Risks of Practice, 2 nd Ed, Stevenson DK and Sunshine P (Eds), Cambridge University Press, Cambridge, UK. Chapter 36, pp 715-734, 2003.
  • Gunn AJ, Bennet L. Responses of the fetus and neonate to hypothermia. In: Fetal & Neonatal Physiology, 3 rd edition. Polin R, Fox, Abman (Eds), W.B. Saunders, Section IX (Thermoregulation), Chapter 58, pp 42–48, 2003.
  • Tonkin SL, Vogel S, Gunn AJ. The relevance to sudden death of the anatomy of the infant upper airway passages and the identification of those infants at possible risk. In: Sudden Infant Death. Jenik A (Ed), in press, 2004.
  • Gunn AJ, Bennet L. Neonatal Encephalopathy. In: Therapeutic Hypothermia, Tisherman S (Ed). In press, 2004.
  • Guan J, Bennet L, and Gunn AJ. Treatment in Animal Models, In: IGF-1 and IGF binding protein assessment and therapeutic benefit". S Ciafarani , DR Clemmons and MO Savage (Eds), Volume 8, book series Endocrine Development, in press, Sept 2004.
  • Guan J, Bennet L and Gunn AJ. Experimental therapies for hypoxia-ischemia. In: Progress in Cerebral Palsy. In press, 2004.
  • Guan J, Bennet L and Gunn AJ. Experimental therapies for hypoxia-ischemia. In: Progress in Cerebral Palsy. In press, 2004