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Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia-Ischemia Brain Injury.
- Source :
-
Anesthesiology . Jul2016, Vol. 125 Issue 1, p180-192. 13p. - Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>Hypoxic-ischemic encephalopathy is a major cause of mortality and disability in the newborn. The authors investigated the protective effects of argon combined with hypothermia on neonatal rat hypoxic-ischemic brain injury.<bold>Methods: </bold>In in vitro studies, rat cortical neuronal cell cultures were challenged by oxygen and glucose deprivation for 90 min and exposed to 70% Ar or N2 with 5% CO2 balanced with O2, at 33°C for 2 h. Neuronal phospho-Akt, heme oxygenase-1 and phospho-glycogen synthase kinase-3β expression, and cell death were assessed. In in vivo studies, neonatal rats were subjected to unilateral common carotid artery ligation followed by hypoxia (8% O2 balanced with N2 and CO2) for 90 min. They were exposed to 70% Ar or N2 balanced with oxygen at 33°, 35°, and 37°C for 2 h. Brain injury was assessed at 24 h or 4 weeks after treatment.<bold>Results: </bold>In in vitro studies, argon-hypothermia treatment increased phospho-Akt and heme oxygenase-1 expression and significantly reduced the phospho-glycogen synthase kinase-3β Tyr-216 expression, cytochrome C release, and cell death in oxygen-glucose deprivation-exposed cortical neurons. In in vivo studies, argon-hypothermia treatment decreased hypoxia/ischemia-induced brain infarct size (n = 10) and both caspase-3 and nuclear factor-κB activation in the cortex and hippocampus. It also reduced hippocampal astrocyte activation and proliferation. Inhibition of phosphoinositide-3-kinase (PI3K)/Akt pathway through LY294002 attenuated cerebral protection conferred by argon-hypothermia treatment (n = 8).<bold>Conclusion: </bold>Argon combined with hypothermia provides neuroprotection against cerebral hypoxia-ischemia damage in neonatal rats, which could serve as a new therapeutic strategy against hypoxic-ischemic encephalopathy. [ABSTRACT FROM AUTHOR]
- Subjects :
- *THERAPEUTIC use of gases
*ANIMAL experimentation
*ANIMAL populations
*CELL culture
*CELL death
*CELL physiology
*CELLS
*COMBINED modality therapy
*GASES
*HEMOPROTEINS
*INDUCED hypothermia
*NEURONS
*OXIDOREDUCTASES
*RATS
*RESEARCH funding
*TRANSFERASES
*NEUROPROTECTIVE agents
*CEREBRAL anoxia-ischemia
*PHARMACODYNAMICS
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 00033022
- Volume :
- 125
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Anesthesiology
- Publication Type :
- Academic Journal
- Accession number :
- 116282933
- Full Text :
- https://doi.org/10.1097/ALN.0000000000001128