1. Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a swine model of neonatal hypoxic-ischemic encephalopathy
- Author
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Hui Zhang, Junchao Zhu, Raymond C. Koehler, Ewa Kulikowicz, Nicole Moy, Zeng Jin Yang, Jeong Hoo Lee, Dawn Spicer, Bing Wang, Utpal Bhalala, Jillian S. Armstrong, Michael Reyes, Jennifer K. Lee, and Lee J. Martin
- Subjects
Swine ,animal diseases ,Encephalopathy ,H&E stain ,Apoptosis ,Neuroprotection ,Infant, Newborn, Diseases ,fluids and secretions ,Hypothermia, Induced ,Piriform cortex ,Medicine ,Animals ,Humans ,Asphyxia ,Neurons ,TUNEL assay ,integumentary system ,business.industry ,Infant, Newborn ,Motor Cortex ,Hypothermia ,medicine.disease ,Disease Models, Animal ,medicine.anatomical_structure ,Neurology ,Animals, Newborn ,Cerebral cortex ,Anesthesia ,Caspases ,Hypoxia-Ischemia, Brain ,Original Article ,Neurology (clinical) ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - 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.
- Published
- 2014