Article tools
Author information
Published in Volume 99, Issue 2 (January 15,1997)
J. Clin. Invest. 99(2): 248-256 (1997). doi:10.1172/JCI119153.
Copyright © 1997, The American Society for Clinical Investigation.

Research Article

Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs.

A J Gunn, T R Gunn, H H de Haan, C E Williams and P D Gluckman

Research Centre for Developmental Medicine and Biology, Department of Paediatrics, School of Medicine, University of Auckland, New Zealand. aj.gunn@auckland.ac.nz

Published January 15, 1997

Hypothermia has been proposed as a neuroprotective strategy. However, short-term cooling after hypoxia-ischemia is effective only if started immediately during resuscitation. The aim of this study was to determine whether prolonged head cooling, delayed into the late postinsult period, improves outcome from severe ischemia. Unanesthetized near term fetal sheep were subject to 30 min of cerebral ischemia. 90 min later they were randomized to either cooling (n = 9) or sham cooling (n = 7) for 72 h. Intrauterine cooling was induced by a coil around the fetal head, leading initially to a fall in extradural temperature of 5-10 degrees C, and a fall in esophageal temperature of 1.5-3 degrees C. Cooling was associated with mild transient systemic metabolic effects, but not with hypotension or altered fetal heart rate. Cerebral cooling reduced secondary cortical cytotoxic edema (P < 0.001). After 5 d of recovery there was greater residual electroencephalogram activity (-5.2+/-1.6 vs. -15.5+/-1.5 dB, P < 0.001) and a dramatic reduction in the extent of cortical infarction and neuronal loss in all regions assessed (e.g., 40 vs. 99% in the parasagittal cortex, P < 0.001). Selective head cooling, maintained throughout the secondary phase of injury, is noninvasive and safe and shows potential for improving neonatal outcome after perinatal asphyxia.

This article Copyright © 1997, The American Society for Clinical Investigation.

Articles that cite
this article:

Pathophysiology of an hypoxic–ischemic insult during the perinatal period
John W. Calvert, John H. Zhang
neurol res 27(3):246. [CrossRef]

Analysis of Neuronal, Glial, Endothelial, Axonal and Apoptotic Markers Following Moderate Therapeutic Hypothermia and Anesthesia in the Developing Piglet Brain
Pierre Gressens, John Dingley, Frank Plaisant, Helen Porter, Leslie Schwendimann, Catherine Verney, James Tooley, Marianne Thoresen
Brain Pathol 18(1):10. [CrossRef]

Therapeutic hypothermia: from lab to NICU
Alistair Jan Gunn, Malcolm Battin, Peter D. Gluckman, Tania R. Gunn, Laura Bennet
J Perinat Med 33(4):340. [CrossRef]

Perinatal brain injury
Richard Berger, Yves Garnier
J Perinat Med 28(4):261. [CrossRef]

Proinflammatory cytokines and interleukin-9 exacerbate excitotoxic lesions of the newborn murine neopallium
Marie-Aliette Dommergues, Juliana Patkai, Jean-Christophe Renauld, Philippe Evrard, Pierre Gressens
Ann Neurol 47(1):54. [CrossRef]

Extracellular amino acids and lipid peroxidation products in periventricular white matter during and after cerebral ischemia in preterm fetal sheep
Mhoyra Fraser, Laura Bennet, Pierre L. Van zijl, Tessa J. Mocatta, Christopher E. Williams, Peter D. Gluckman, Christine C. Winterbourn, Alistair J. Gunn
J Neurochem 105(6):2214. [CrossRef]

Brain-regulated metabolic suppression during hibernation: a neuroprotective mechanism for perinatal hypoxia–ischemia
Thomas I. Nathaniel
Int J Stroke 3(2):98. [CrossRef]

Strategies for the management of neonatal hypoxic–ischemic brain injury
Jeffrey M Perlman
3(3):379. [CrossRef]

Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit
Z-L Lin, H-M Yu, J Lin, S-Q Chen, Z-Q Liang, Z-Y Zhang
J Perinatol 26(3):180. [CrossRef]

Some like it cool: hypothermia for newborn infants with hypoxic ischemic encephalopathy
O D Saugstad
J Perinatol 26(3):144. [CrossRef]

Effects of rapid rewarming on cerebral nitric oxide production and cerebral hemodynamics after hypothermia therapy for kainic acid-induced seizures in immature rabbits
Yukito Takei, Daisuke Sunohara, Yasushi Nishikawa, Chikako Nagashima, Maki Tachibana, Takeshi Takami, Tasuku Miyajima, Akinori Hoshika
Pediatr Int 47(1):53. [CrossRef]

The cardiovascular and cerebrovascular responses of the immature fetal sheep to acute umbilical cord occlusion
L. Bennet, S. Rossenrode, M. I. Gunning, P. D. Gluckman, A. J. Gunn
J Physiol 517(1):247. [CrossRef]

Window of Opportunity of Cerebral Hypothermia for Postischemic White Matter Injury in the Near-Term Fetal Sheep
Vincent Roelfsema, Laura Bennet, Sherly George, David Wu, Jian Guan, Marije Veerman, Alistair Jan Gunn
J Cereb Blood Flow Metab [CrossRef]

Rapid Brain Cooling by Hypothermic Retrograde Jugular Vein Flush
Yi-Szu Wen, Mu-Shung Huang, Mao-Tsun Lin, Chen-Hsen Lee
Journal of Trauma Injury Infection and Critical Care 58(3):577. [CrossRef]

Depth of delayed cooling alters neuroprotection pattern after hypoxia-ischemia
Osuke Iwata, John S. Thornton, Mark W. Sellwood, Sachiko Iwata, Yasuko Sakata, Martina A. Noone, Frances E. O'brien, Alan Bainbridge, Enrico De vita, Gennadij Raivich
Ann Neurol 58(1):75. [CrossRef]


Shannon Hamrick, Donna Ferriero
Curr Opin Neurol 16(2):147. [CrossRef]

Therapeutic hypothermia for hypoxic???ischaemic encephalopathy in the newborn infant: review
Marianne Thoresen, Andrew Whitelaw
Curr Opin Neurol 18(2):111???116. [CrossRef]


Alistair Gunn
Curr Opin Pediatr 12(2):111. [CrossRef]


Andrew Whitelaw, Marianne Thoresen
Curr Opin Pediatr 14(6):664. [CrossRef]

Brain temperature in newborn piglets under selective head cooling with minimal systemic hypothermia
Osuke Iwata, Sachiko Iwata, Masanori Tamura, Tomohiko Nakamura, Masatoshi Sugiura, Yoshifumi Ogiso
Pediatr Int 45(2):163. [CrossRef]

Systemic hypothermia to decrease morbidity of hypoxic-ischemic brain injury
R A Polin, T M Randis, R Sahni
J Perinatol [CrossRef]

Cerebral oxygenation during postasphyxial seizures in near-term fetal sheep
Hernan Gonzalez, Christian J Hunter, Laura Bennet, Gordon G Power, Alistair J Gunn
J Cereb Blood Flow Metab 25(7):911. [CrossRef]

Coupling of Cerebral Blood Flow and Oxygen Metabolism in Infant Pigs During Selective Brain Hypothermia
Bernd Walter, Reinhard Bauer, Gernot Kuhnen, Harald Fritz, Ulrich Zwiener
J Cereb Blood Flow Metab [CrossRef]

Insulin-like Growth Factor-1 Reduces Postischemic White Matter Injury in Fetal Sheep
Jian Guan, Laura Bennet, Shirley George, David Wu, Harry J. Waldvogel, Peter D. Gluckman, Richard L. M. Faull, Philip S. Crosier, Alistair J. Gunn
J Cereb Blood Flow Metab [CrossRef]

Effects of Hypothermia on Energy Metabolism in Mammalian Central Nervous System
Maria Erecinska, Marianne Thoresen, Ian A. Silver
J Cereb Blood Flow Metab [CrossRef]

Induced hypothermia: A novel neuroprotective treatment of neonatal encephalopathy after intrapartum hypoxia-ischemia
Jeffrey Perlman
Curr Treat Options Neurol 7(6):451. [CrossRef]

Theoretical limits on brain cooling by external head cooling devices
A. L. Sukstanskii, D. A. Yablonskiy
Eur J Appl Physiol 101(1):41. [CrossRef]

Hypothermia as a Treatment for Birth Asphyxia
SEETHA Shankaran, ABBOT R. Laptook
Clin Obstet Gynec 50(3):624. [CrossRef]

Head Cooling for Neonatal Encephalopathy: The State of the Art
ALISTAIR JAN Gunn, PETER D. Gluckman
Clin Obstet Gynec 50(3):636. [CrossRef]

A review of selective hypothermia in the management of traumatic brain injury
Eisha Christian, Gabriel Zada, Gene Sung, Steven L. Giannotta
Neurosurg Focus 25(4):E9. [CrossRef]

Cochrane Review: Cooling for newborns with hypoxic ischaemic encephalopathy
Susan E Jacobs, Rod Hunt, William O Tarnow-mordi, Terrie E Inder, Peter G Davis
Evid -Based Child Health 3(4):1049. [CrossRef]

Keeping a cool head, post-hypoxic hypothermia–an old idea revisited
M. Thoresen, J. Wyatt
Acta Paediatr Suppl 86(10):1029. [CrossRef]

Delayed Hypothermia as Selective Head Cooling or Whole Body Cooling Does Not Protect Brain or Body in Newborn Pig Subjected to Hypoxia-Ischemia
MATHIAS Karlsson, JAMES R. Tooley, SAULIUS Satas, CATHERINE E. Hobbs, ELA Chakkarapani, JANET Stone, HELEN Porter, MARIANNE Thoresen
Pediatr Res 64(1):74. [CrossRef]