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Stroke. 2015 Jan;46(1):275-8. doi: 10.1161/STROKEAHA.114.007330. Epub 2014 Nov 25.

Brain cell death is reduced with cooling by 3.5°C to 5°C but increased with cooling by 8.5°C in a piglet asphyxia model.

Author information

1
From the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.).
2
From the Institute for Women's Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King's College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United Kingdom (X.G.). n.robertson@ucl.ac.uk.

Abstract

BACKGROUND AND PURPOSE:

In infants with moderate to severe neonatal encephalopathy, whole-body cooling at 33°C to 34°C for 72 hours is standard care with a number needed to treat to prevent a adverse outcome of 6 to 7. The precise brain temperature providing optimal neuroprotection is unknown.

METHODS:

After a quantified global cerebral hypoxic-ischemic insult, 28 piglets aged <24 hours were randomized (each group, n=7) to (1) normothermia (38.5°C throughout) or whole-body cooling 2 to 26 hours after insult to (2) 35°C, (3) 33.5°C, or (4) 30°C. At 48 hours after hypoxia-ischemia, delayed cell death (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and cleaved caspase 3) and microglial ramification (ionized calcium-binding adapter molecule 1) were evaluated.

RESULTS:

At 48 hours after hypoxia-ischemia, substantial cerebral injury was found in the normothermia and 30°C hypothermia groups. However, with 35°C and 33.5°C cooling, a clear reduction in delayed cell death and microglial activation was observed in most brain regions (P<0.05), with no differences between 35°C and 33.5°C cooling groups. A protective pattern was observed, with U-shaped temperature dependence in delayed cell death in periventricular white matter, caudate nucleus, putamen, hippocampus, and thalamus. A microglial activation pattern was also seen, with inverted U-shaped temperature dependence in periventricular white matter, caudate nucleus, internal capsule, and hippocampus (all P<0.05).

CONCLUSIONS:

Cooling to 35°C (an absolute drop of 3.5°C as in therapeutic hypothermia protocols) or to 33.5°C provided protection in most brain regions after a cerebral hypoxic-ischemic insult in the newborn piglet. Although the relatively wide therapeutic range of a 3.5°C to 5°C drop in temperature reassured, overcooling (an 8.5°C drop) was clearly detrimental in some brain regions.

KEYWORDS:

hypothermia; hypoxia-ischemia, brain; neonatal encephalopathy; neuroprotection

PMID:
25424475
PMCID:
PMC4276417
DOI:
10.1161/STROKEAHA.114.007330
[Indexed for MEDLINE]
Free PMC Article

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