Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia-Ischemia Brain Injury

• Background: 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. Methods: 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 N-2 with 5% CO2 balanced with O-2, at 33 degrees C for 2 h. Neuronal phospho-Akt, heme oxygenase-1 and phospho-glycogen synthase kinase-3a expression, and cell death were assessed. In in vivo studies, neonatal rats were subjected to unilateral common carotid artery ligation followed by hypoxia (8% O-2 balanced with N-2 and CO2) for 90 min. They were exposed to 70% Ar or N-2 balanced with oxygen at 33 degrees, 35 degrees, and 37 degrees C for 2 h. Brain injury was assessed at 24 h or 4 weeks after treatment. Results: In in vitro studies, argon-hypothermia treatment increased phospho-Akt and heme oxygenase-1 expression and significantly reduced the phospho-glycogen synthase kinase-3 beta 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-kappa B activation in the cortex and -hippocampus. It also reduced hippocampal astrocyte activation and proliferation. Inhibition of phosphoinositide-3-kinase (PI 3K)/Akt pathway through LY294002 attenuated cerebral protection conferred by argon-hypothermia treatment (n = 8). Conclusion: 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)

Nyckelord

cell-death

term neuroprotection

neuronal injury

noble-gases

xenon

rats

asphyxia

model

akt

neurodegeneration

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)