How long is sufficient for optimal neuroprotection with cerebral cooling after ischemia in fetal sheep?

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Joanne O DavidsonAlistair J Gunn

Abstract

The optimal duration of mild "therapeutic" hypothermia for neonates with hypoxic-ischemic encephalopathy is surprisingly unclear. This study assessed the relative efficacy of cooling for 48 h versus 72 h. Fetal sheep (0.85 gestation) received sham ischemia (n = 9) or 30 min global cerebral ischemia followed by normothermia (n = 8) or delayed hypothermia from 3 h to 48 h (n = 8) or 72 h (n = 8). Ischemia was associated with profound loss of electroencephalogram (EEG) power, neurons in the cortex and hippocampus, and oligodendrocytes and myelin basic protein expression in the white matter, with increased Iba-1-positive microglia and proliferation. Hypothermia for 48 h was associated with improved outcomes compared to normothermia, but a progressive deterioration of EEG power after rewarming compared to 72 h of hypothermia, with impaired neuronal survival and myelin basic protein, and more microglia in the white matter and cortex. These findings show that head cooling for 48 h is partially neuroprotective, but is inferior to cooling for 72 h after cerebral ischemia in fetal sheep. The close association between rewarming at 48 h, subsequent deterioration in EEG power and increased cortical inflammation strongly suggests that delete...Continue Reading

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Citations

Aug 11, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Joanne O DavidsonAlistair J Gunn
Aug 29, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Raymond C KoehlerLee J Martin
Oct 20, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jingyan ZhaoXunming Ji
Sep 9, 2018·Archives of Disease in Childhood. Fetal and Neonatal Edition·Joanne O DavidsonAlistair J Gunn
Aug 15, 2019·Pediatric Research·Robert GalinskyAlistair J Gunn
Nov 22, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Patrick D LydenPadmesh S Rajput
Sep 25, 2017·Archives of Disease in Childhood. Fetal and Neonatal Edition·Peter J LallySudhin Thayyil
Jul 3, 2020·Developmental Medicine and Child Neurology·Kelly Q ZhouAlistair J Gunn
Mar 3, 2020·Pediatrics International : Official Journal of the Japan Pediatric Society·Kenta Ht ChoAlistair J Gunn
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Jul 19, 2021·Seminars in Fetal & Neonatal Medicine·Joanne O DavidsonUNKNOWN Newborn Brain Society Guidelines and Publications Committee

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Methods Mentioned

BETA
light microscopy

Software Mentioned

ImageJ
ARRIVE
LabView

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