Dataset Information

Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxic-ischemic encephalopathy.

ABSTRACT: The consequences of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy are poorly understood. Adverse effects from suboptimal rewarming could diminish neuroprotection from hypothermia. Therefore, we tested whether rewarming is associated with apoptosis. Piglets underwent hypoxia-asphyxia followed by normothermic or hypothermic recovery at 2 hours. Hypothermic groups were divided into those with no rewarming, rewarming at 0.5 °C/hour, or rewarming at 4 °C/hour. Neurodegeneration at 29 hours was assessed by hematoxylin and eosin staining, TUNEL assay, and immunoblotting for cleaved caspase-3. Rewarmed piglets had more apoptosis in motor cortex than did those that remained hypothermic after hypoxia-asphyxia. Apoptosis in piriform cortex was greater in hypoxic-asphyxic, rewarmed piglets than in naive/sham piglets. Caspase-3 inhibitor suppressed apoptosis with rewarming. Rapidly rewarmed piglets had more caspase-3 cleavage in cerebral cortex than did piglets that remained hypothermic or piglets that were rewarmed slowly. We conclude that rewarming from therapeutic hypothermia can adversely affect the newborn brain by inducing apoptosis through caspase mechanisms.

SUBMITTER: Wang B

PROVIDER: S-EPMC4420851 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxic-ischemic encephalopathy.

Wang Bing B Armstrong Jillian S JS Lee Jeong-Hoo JH Bhalala Utpal U Kulikowicz Ewa E Zhang Hui H Reyes Michael M Moy Nicole N Spicer Dawn D Zhu Junchao J Yang Zeng-Jin ZJ Koehler Raymond C RC Martin Lee J LJ Lee Jennifer K JK

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20150107 5

The consequences of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy are poorly understood. Adverse effects from suboptimal rewarming could diminish neuroprotection from hypothermia. Therefore, we tested whether rewarming is associated with apoptosis. Piglets underwent hypoxia-asphyxia followed by normothermic or hypothermic recovery at 2 hours. Hypothermic groups were divided into those with no rewarming, rewarming at 0.5 °C/hour, or rewarming at 4 °C/hour. Neurodegeneration ...[more]

PMID: 25564240

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Project description:Early induced therapeutic hypothermia represents the cornerstone treatment in neonates with probable hypoxic-ischemic encephalopathy. The selection of patients for treatment usually involves meeting criteria indicating evidence of perinatal hypoxia-ischemia and the presence of moderate or severe encephalopathy. In this review, we highlight the variability that exists between some of the different regional and national eligibility guidelines. Determining the potential presence of perinatal hypoxia-ischemia may require either one, two or three signs amongst history of acute perinatal event, prolonged resuscitation at delivery, abnormal blood gases and low Apgar score, with a range of cutoff values. Clinical neurological exams often define the severity of encephalopathy differently, with varying number of domains required for determining eligibility and blurred interpretation of findings assigned to different severity grades in different systems. The role of early electrophysiological assessment is weighted differently. A clinical implication is that infants may receive different care depending on the location in which they are born. This could also impact epidemiological data, as inference of rates of moderate-severe encephalopathy based on therapeutic hypothermia rates are misleading and influenced by different eligibility methods used. We would advocate that a universally endorsed single severity staging of encephalopathy is vital for standardizing management and neonatal outcome. IMPACT: Variability exists between regional and national therapeutic hypothermia eligibility guidelines for neonates with probable hypoxic-ischemic encephalopathy. Differences are common in both criteria indicating perinatal hypoxia-ischemia and criteria defining moderate or severe encephalopathy. The role of early electrophysiological assessment is also weighted unequally. This reflects in different individual care and impacts research data. A universally endorsed single severity staging of encephalopathy would be crucial for standardizing management.

Dataset Information

Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxic-ischemic encephalopathy.

Publications

Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxic-ischemic encephalopathy.

Similar Datasets

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