Melatonin Administration from 2000 to 2020 to Human Newborns with Hypoxic-Ischemic Encephalopathy

Author(s):  
Gabriella D'angelo ◽  
Laura Cannavò ◽  
Russel J. Reiter ◽  
Eloisa Gitto

Hypoxic-ischemic encephalopathy (HIE) is the main cause of long-term neurodevelopmental morbidity in term born infants worldwide. Melatonin is a hormone with antioxidant and anti-inflammatory effects that make it a promising molecule for the treatment of perinatal asphyxia. Probably, the synergistic use of hypothermia associated with melatonin treatment may improve the neurological outcome in infants with HIE. In the past 20 years, the efficacy of melatonin in reducing oxidative stress has been demonstrated in animals; however, clinical trials with sufficient sample size of newborns are lacking to date.Since in 2000 we were among the first to study the neuroprotective properties of melatonin on infants, in this review, we want to summarize the advantages and limitations of the investigations conducted to date. Key Points

Author(s):  
Shreyas Ramachandran ◽  
Smiti Sripathi

Background: Hypoxic ischemic encephalopathy (HIE) is one the common causes of neonatal fatality due to perinatal asphyxia. The long-term outcomes of HIE are impaired mental and motor development, hearing loss, recurrent seizures and cerebral palsy. MRI is increasingly becoming the gold standard in diagnosis of HIE as it involves no radiation and can be performed during a neonates physiological sleep. To evaluate the role of MRI in infants with suspected hypoxic ischemic encephalopathy in prognosticating neurological outcomes at end of one year.Methods: A total of 50 patients were included in the study who underwent MRI of brain. A clinical follow up was done at the end of one year.Results: The sensitivity of MRI in prognosticating clinical outcome was 72% and specificity was 71% while PPV and NPV was 86% and 50% respectively.Conclusions: MRI is a useful modality to assess early changes in HIE and it can prognosticate clinical outcome.


2020 ◽  
Vol 21 (4) ◽  
pp. 1487 ◽  
Author(s):  
Dorothy E. Oorschot ◽  
Rachel J. Sizemore ◽  
Ashraf R. Amer

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.


2021 ◽  
Vol 22 (9) ◽  
pp. 4822
Author(s):  
Viktória Kovács ◽  
Gábor Remzső ◽  
Tímea Körmöczi ◽  
Róbert Berkecz ◽  
Valéria Tóth-Szűki ◽  
...  

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.


2020 ◽  
Vol 159 ◽  
pp. S115
Author(s):  
Mari Merce Cascant Vilaplana ◽  
Ángel Sánchez-Illana ◽  
José David Piñeiro-Ramos ◽  
Guillermo Quintás ◽  
Camille Oger ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 569
Author(s):  
Jean-Nicolas Tournier ◽  
Joseph Kononchik

The eradication of infectious diseases has been achieved only once in history, in 1980, with smallpox. Since 1988, significant effort has been made to eliminate poliomyelitis viruses, but eradication is still just out of reach. As the goal of viral disease eradication approaches, the ability to recreate historically eradicated viruses using synthetic biology has the potential to jeopardize the long-term sustainability of eradication. However, the emergence of the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic has highlighted our ability to swiftly and resolutely respond to a potential outbreak. This virus has been synthetized faster than any other in the past and is resulting in vaccines before most attenuated candidates reach clinical trials. Here, synthetic biology has the opportunity to demonstrate its truest potential to the public and solidify a footing in the world of vaccines.


2015 ◽  
Vol 31 (6) ◽  
pp. 797-803 ◽  
Author(s):  
Jichong Huang ◽  
Jun Tang ◽  
Yi Qu ◽  
Li Zhang ◽  
Yan Zhou ◽  
...  

2013 ◽  
Vol 163 (4) ◽  
pp. 949-954 ◽  
Author(s):  
Vishal S. Kapadia ◽  
Lina F. Chalak ◽  
Tara L. DuPont ◽  
Nancy K. Rollins ◽  
Luc P. Brion ◽  
...  

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