Xenon Combined With Hypothermia in Perinatal Hypoxic-Ischemic Encephalopathy: A Noble Gas, a Noble Mission

Amer, Ashraf R.; Oorschot, Dorothy E.

doi:10.1016/j.pediatrneurol.2018.02.009

Cited by 22 publications

(17 citation statements)

References 88 publications

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“…Amelioration of the process of ongoing brain injury through neuroprotective and neurorestorative interventions [9,11]. Neuroprotective interventions are delivered within 6 h of HIE, while neurorestorative interventions have a delayed onset.…”

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confidence: 99%

“…We recently reviewed the current literature on combining HT with xenon. We concluded that, while preclinical research provides supportive evidence, the routine use of this combined therapy awaits more clinical trials and the overcoming of major logistical constraints in the clinic to achieve timely post-hypoxic delivery of xenon [11]. Here we review the use of HT in combination with EPO for the treatment of perinatal HIE at term.…”

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confidence: 99%

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Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research

Oorschot

Sizemore

Amer

2020

IJMS

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Perinatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of morbidity and mortality. Moderate hypothermia (33.5 °C) is currently the sole established standard treatment. However, there are a large number of infants for whom this therapy is ineffective. This inspired global research to find neuroprotectants to potentiate the effect of moderate hypothermia. Here we examine erythropoietin (EPO) as a prominent candidate. Neonatal animal studies show that immediate, as well as delayed, treatment with EPO post-injury, can be neuroprotective and/or neurorestorative. The observed improvements of EPO therapy were generally not to the level of control uninjured animals, however. This suggested that combining EPO treatment with an adjunct therapeutic strategy should be researched. Treatment with EPO plus hypothermia led to less cerebral palsy in a non-human primate model of perinatal asphyxia, leading to clinical trials. A recent Phase II clinical trial on neonatal infants with HIE reported better 12-month motor outcomes for treatment with EPO plus hypothermia compared to hypothermia alone. Hence, the effectiveness of combined treatment with moderate hypothermia and EPO for neonatal HIE currently looks promising. The outcomes of two current clinical trials on neurological outcomes at 18–24 months-of-age, and at older ages, are now required. Further research on the optimal dose, onset, and duration of treatment with EPO, and critical consideration of the effect of injury severity and of gender, are also required.

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confidence: 99%

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confidence: 99%

Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research

Oorschot

Sizemore

Amer

2020

IJMS

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“…Xenon can also be used as an adjuvant with hypothermia therapy to treat neonatal HIE and has been proven to be effective in reducing brain injury and improving long-term recovery (Ma et al, 2005;Chakkarapani et al, 2010;Amer and Oorschot, 2018). However, at present, there is not enough evidence to support xenon as a conventional clinical adjuvant neuroprotective agent (Rüegger et al, 2017;Amer and Oorschot, 2018). Hence, further studies are required to optimize its application for human neonatal hypoxia ischemia.…”

Section: Treatment Of Neonatal Hypoxic-ischemic Encephalopathymentioning

confidence: 99%

The Function of the NMDA Receptor in Hypoxic-Ischemic Encephalopathy

2020

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Hypoxic-ischemic encephalopathy (HIE) is one of the main forms of neonatal brain injury which could lead to neonatal disability or even cause neonatal death. Therefore, HIE strongly affects the health of newborns and brings heavy burden to the family and society. It has been well studied that N-methyl-D-aspartate (NMDA) receptors are involved in the excitotoxicity induced by hypoxia ischemia in adult brain. Recently, it has been shown that the NMDA receptor also plays important roles in HIE. In the present review, we made a summary of the molecular mechanism of NMDA receptor in the pathological process of HIE, focusing on the distinct role of GluN2A-and GluN2Bcontaining NMDA receptor subtypes and aiming to provide some insights into the clinical treatment and drug development of HIE.

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“…However, the widespread clinical application of xenon is hampered by the difficulty of its separation and its scarce availability. Nevertheless, the potential neuroprotective effect of xenon has been the focus of scientific research 97. Xenon alleviates oxidative stress, reduces N-methyl-D-aspartate receptor mediated neurodegeneration and exerts both neurotrophic as well as neuroprotective effects in cholinergic neurons 6465.…”

Section: Inert Gasesmentioning

confidence: 99%

Recent advances in the neuroprotective effects of medical gases

Wang¹,

Li²,

Cao³

et al. 2019

Med Gas Res

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Central nervous system injuries are a leading cause of death and disability worldwide. Although the exact pathophysiological mechanisms of various brain injuries vary, central nervous system injuries often result in an inflammatory response, and subsequently lead to brain damage. This suggests that neuroprotection may be necessany in the treatment of multiple disease models. The use of medical gases as neuroprotective agents has gained great attention in the medical field. Medical gases include common gases, such as oxygen, hydrogen and carbon dioxide; hydrogen sulphide and nitric oxide that have been considered toxic; volatile anesthetic gases, such as isoflurane and sevoflurane; and inert gases like helium, argon, and xenon. The neuroprotection from these medical gases has been investigated in experimental animal models of various types of brain injuries, such as traumatic brain injury, stroke, subarachnoid hemorrhage, cerebral ischemic/reperfusion injury, and neurodegenerative diseases. Nevertheless, the transition into the clinical practice is still lagging. This delay could be attributed to the contradictory paradigms and the conflicting results that have been obtained from experimental models, as well as the presence of inconsistent reports regarding their safety. In this review, we summarize the potential mechanisms underlying the neuroprotective effects of medical gases and discuss possible candidates that could improve the outcomes of brain injury.

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Xenon Combined With Hypothermia in Perinatal Hypoxic-Ischemic Encephalopathy: A Noble Gas, a Noble Mission

Cited by 22 publications

References 88 publications

Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research

Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research

The Function of the NMDA Receptor in Hypoxic-Ischemic Encephalopathy

Recent advances in the neuroprotective effects of medical gases

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