Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Ma, Daqing; Hossain, Mahmuda; Pettet, Garry K J; Luo, Yan; Lim, Ta; Akimov, Stanislav; Sanders, Robert D.; Franks, Nicholas P.; Maze, Mervyn

doi:10.1038/sj.jcbfm.9600184

Cited by 166 publications

(127 citation statements)

References 45 publications

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“…The absence of a safe and effective therapy for hypoxia-ischemia brain injury in newborns has prompted the investigation of the possible protective effects of noble gases, especially xenon 19 . Argon, another noble gas, possesses similar protective properties 20 .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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 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. Results 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). 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Accordingly, the organ-protective properties of Xe preconditioning have been demonstrated for the heart 9 and brain. 10 Here, we show that Xe preconditioning protects against IRI to the kidney in mice and that the mechanism is due to increased expression of HIF-1␣ as well as its downstream effectors through enhanced translational efficiency involving the mammalian target of rapamycin (mTOR) pathway.…”

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Xenon Preconditioning Protects against Renal Ischemic-Reperfusion Injury via HIF-1α Activation

Lim

et al. 2009

Journal of the American Society of Nephrology

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The mortality rate from acute kidney injury after major cardiovascular operations can be as high as 60%, and no therapies have been proved to prevent acute kidney injury in this setting. Here, we show that preconditioning with the anesthetic gas xenon activates hypoxia-inducible factor 1␣ (HIF-1␣) and its downstream effectors erythropoietin and vascular endothelial growth factor in a time-dependent manner in the kidneys of adult mice. Xenon increased the efficiency of HIF-1␣ translation via modulation of the mammalian target of rapamycin pathway. In a model of renal ischemia-reperfusion injury, xenon provided morphologic and functional renoprotection; hydrodynamic injection of HIF-1␣ small interfering RNA demonstrated that this protection is HIF-1␣ dependent. These results suggest that xenon preconditioning is a natural inducer of HIF-1␣ and that administration of xenon before renal ischemia can prevent acute renal failure. If these data are confirmed in the clinical setting, then preconditioning with xenon may be beneficial before procedures that temporarily interrupt renal perfusion.

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“…14,15 Volatile anesthetics, such as sevoflurane, have also been shown to protect myocardium from ischemic injury in a preconditioning setting. 16,17 Furthermore, sevoflurane (0.8% in oxygen) has recently been shown to provide labor analgesia that is superior to that of nitrous oxide (50%)-oxygen 18 ; however, it is unknown whether sevoflurane can precondition against perinatal asphyxial injury like xenon can.…”

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Xenon and Sevoflurane Protect against Brain Injury in a Neonatal Asphyxia Model

Luo

Ieong

et al. 2008

Anesthesiology

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Background: Perinatal hypoxia-ischemia causes significant morbidity and mortality. Xenon and sevoflurane may be used as inhalational analgesics for labor. Therefore, the authors investigated the potential application of these agents independently and in combination to attenuate perinatal injury.Methods: Oxygen-glucose deprivation injury was induced in pure neuronal or neuronal-glial cocultures 24 h after preconditioning with xenon and/or sevoflurane. Cell death was assessed by lactate dehydrogenase release or staining with annexin V-propidium iodide. The mediating role of phosphoinositide-3-kinase signaling in putative protection was assessed using wortmannin, its cognate antagonist. In separate in vivo experiments, perinatal asphyxia was induced 4 hours after preconditioning with analgesic doses alone and in combination; infarct size was assessed 7 days later, and neuromotor function was evaluated at 30 days in separate cohorts. The role of phosphorylated cyclic adenosine monophosphate response element binding protein in the preconditioning was assessed by immunoblotting.Results: Both anesthetics preconditioned against oxygen-glucose deprivation in vitro alone and in combination. The combination increased cellular viability via phosphoinositide-3-kinase signaling. In in vivo studies, xenon (75%) and sevoflurane (1.5%) alone as well as in combination (20% xenon and 0.75% sevoflurane) reduced infarct size in a model of neonatal asphyxia. Preconditioning with xenon and the combination of xenon and sevoflurane resulted in long-term functional neuroprotection associated with enhanced phosphorylated cyclic adenosine monophosphate response element binding protein signaling.Conclusions: Preconditioning with xenon and sevoflurane provided long-lasting neuroprotection in a perinatal hypoxicischemic model and may represent a viable method to preempt neuronal injury after an unpredictable asphyxial event in the perinatal period.

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Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Cited by 166 publications

References 45 publications

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

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

Xenon Preconditioning Protects against Renal Ischemic-Reperfusion Injury via HIF-1α Activation

Xenon and Sevoflurane Protect against Brain Injury in a Neonatal Asphyxia Model

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