ArticleDevelopmental neuroscience2016
Hypothermia and Rewarming Activate a Macroglial Unfolded Protein Response Independent of Hypoxic-Ischemic Brain Injury in Neonatal Piglets.
Article in Developmental neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Hemodynamics in infants with hypoxemic ischemic encephalopathy: pathophysiology and beyond.Journal of perinatology : official journal of the California Perinatal Association · 2026Review
- Article
- Proteasome localization and activity in pig brain andFrontiers in cellular neuroscience · 2024Article
- Article
- Review
- Mechanisms of Tertiary Neurodegeneration after Neonatal Hypoxic-Ischemic Brain Damage.Pediatric medicine (Hong Kong, China) · 2022Article
- Article
- Fractional anisotropy from diffusion tensor imaging correlates with acute astrocyte and myelin swelling in neonatal swine models of excitotoxic and hypoxic-ischemic brain injury.The Journal of comparative neurology · 2021Article
- Targeting the mitochondrial permeability transition pore for neuroprotection in a piglet model of neonatal hypoxic-ischemic encephalopathy.Journal of neuroscience research · 2021Article
- Combining Hypothermia and Oleuropein Subacutely Protects Subcortical White Matter in a Swine Model of Neonatal Hypoxic-Ischemic Encephalopathy.Journal of neuropathology and experimental neurology · 2021Article
- Mean Diffusivity in Striatum Correlates With Acute Neuronal Death but Not Lesser Neuronal Injury in a Pilot Study of Neonatal Piglets With Encephalopathy.Journal of magnetic resonance imaging : JMRI · 2020Article
- Spatial T-maze identifies cognitive deficits in piglets 1 month after hypoxia-ischemia in a model of hippocampal pyramidal neuron loss and interneuron attrition.Behavioural brain research · 2019Article
- Biodistribution of Glial Progenitors in a Three Dimensional-Printed Model of the Piglet Cerebral Ventricular System.Stem cells and development · 2019Article
- Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro.International journal for parasitology. Drugs and drug resistance · 2019Article
- Hypoxia-Ischemia and Hypothermia Independently and Interactively Affect Neuronal Pathology in Neonatal Piglets with Short-Term Recovery.Developmental neuroscience · 2019Article
- Perinatal hypoxic-ischemic brain injury in large animal models: Relevance to human neonatal encephalopathy.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Review
- Neonatal cerebrovascular autoregulation.Pediatric research · 2018Review
- Proteasome Biology Is Compromised in White Matter After Asphyxic Cardiac Arrest in Neonatal Piglets.Journal of the American Heart Association · 2018Article
- Cerebral Autoregulation and Conventional and Diffusion Tensor Imaging Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy.Pediatric neurology · 2018Observational
- The search continues: neuroprotection for all neonates with hypoxic-ischemic encephalopathy.Journal of thoracic disease · 2017Article
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Authors and funding
9 authors at 1 institution in 1 country.
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Abstract
Therapeutic hypothermia provides incomplete neuroprotection after hypoxia-ischemia (HI)-induced brain injury in neonates. We previously showed that cortical neuron and white matter apoptosis are promoted by hypothermia and early rewarming in a piglet model of HI. The unfolded protein response (UPR) may be one of the potential mediators of this cell death. Here, neonatal piglets underwent HI or sham surgery followed by 29 h of normothermia, 2 h of normothermia + 27 h of hypothermia or 18 h of hypothermia + rewarming. Piglets recovered for 29 h. Immunohistochemistry for endoplasmic reticulum to nucleus signaling-1 protein (ERN1), a marker of UPR activation, was used to determine the ratios of ERN1+ macroglia and neurons in the motor subcortical white matter and cerebral cortex. The ERN1+ macroglia were immunophenotyped as oligodendrocytes and astrocytes by immunofluorescent colabeling. Temperature (p = 0.046) and HI (p < 0.001) independently affected the ratio of ERN1+ macroglia. In sham piglets, sustained hypothermia (p = 0.011) and rewarming (p = 0.004) increased the ERN1+ macroglia ratio above that in normothermia. HI prior to hypothermia diminished the UPR. Ratios of ERN1+ macroglia correlated with white matter apoptotic profile counts in shams (r = 0.472; p = 0.026), thereby associating UPR activation with white matter apoptosis during hypothermia and rewarming. Accordingly, macroglial cell counts decreased in shams that received sustained hypothermia (p = 0.009) or rewarming (p = 0.007) compared to those in normothermic shams. HI prior to hypothermia neutralized the macroglial cell loss. Neither HI nor temperature affected ERN1+ neuron ratios. In summary, delayed hypothermia and rewarming activate the macroglial UPR, which is associated with white matter apoptosis. HI may decrease the macroglial endoplasmic reticulum stress response after hypothermia and rewarming.
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