Extended Combined Neonatal Treatment With Erythropoietin Plus Melatonin Prevents Posthemorrhagic Hydrocephalus of Prematurity in Rats

Robinson, Shenandoah; Conteh, Fatu S; Oppong, Akosua Y.; Yellowhair, Tracylyn R.; Newville, Jessie; Demerdash, Nagat El; Shrock, Christine; Maxwell, Jessie R.; Jett, Stephen D.; Northington, Frances J.; Jantzie, Lauren L.

doi:10.3389/fncel.2018.00322

Cited by 38 publications

(40 citation statements)

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“…Phase I safety studies and careful incremental dose studies are needed prior to RCTs. There is a growing interest in the combination of agents with different neuroprotection profiles; melatonin with erythropoietin in preterm brain injury shows promise 61 .…”

Section: Scientific Reports |mentioning

confidence: 99%

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

Robertson

Lingam

Meehan

et al. 2020

Sci Rep

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With the current practice of therapeutic hypothermia for neonatal encephalopathy, disability rates and the severity spectrum of cerebral palsy are reduced. Nevertheless, safe and effective adjunct therapies are needed to optimize outcomes. This study's objective was to assess if 18 mg/kg melatonin given rapidly over 2 h at 1 h after hypoxia-ischemia with cooling from 1-13 h was safe, achieved therapeutic levels within 3 h and augmented hypothermic neuroprotection. Following hypoxia-ischemia, 20 newborn piglets were randomized to: (i) Cooling 1-13 h (HT; n = 6); (ii) HT+ 2.5% ethanol vehicle (Ht+V; n = 7); (iii) HT + Melatonin (Ht+M; n = 7). Intensive care was maintained for 48 h; aEEG was acquired throughout, brain MRS acquired at 24 and 48 h and cell death (TUNEL) evaluated at 48 h. There were no differences for insult severity. Core temperature was higher in HT group for first hour after Hi. comparing Ht+M to HT, aEEG scores recovered more quickly by 19 h (p < 0.05); comparing HT+V to HT, aEEG recovered from 31 h (p < 0.05). Brain phosphocreatine/inorganic phosphate and NTP/ exchangeable phosphate were higher at 48 h in HT+M versus Ht (p = 0.036, p = 0.049 respectively). Including both 24 h and 48 h measurements, the rise in Lactate/N-acetyl aspartate was reduced in white (p = 0.030) and grey matter (p = 0.038) after HI. Reduced overall TUNEL positive cells were observed in Ht+M (47.1 cells/mm 2 ) compared to HT (123.8 cells/mm 2 ) (p = 0.0003) and HT+V (97.5 cells/mm 2 ) compared to Ht (p = 0.012). Localized protection was seen in white matter for HT+M versus Ht (p = 0.036) and internal capsule for HT+M compared to Ht (p = 0.001) and HT+V versus Ht (p = 0.006). Therapeutic melatonin levels (15-30mg/l) were achieved at 2 h and were neuroprotective following HI, but ethanol vehicle was partially protective.Intrapartum-related neonatal encephalopathy (NE) is a major healthcare problem. Worldwide in 2010, NE accounted for 287,000 deaths and 400,000 survivors with impairment 1 . NE cannot be prevented in most cases and therapies are limited. The incidence of NE in Western Europe is 1-3/1000 term births and in low-and mid-resource settings the incidence is ~10 times higher 1,2 . Over the last 2 decades, in settings with neonatal intensive care facilities, therapeutic hypothermia (HT) is routinely used for moderate-to-severe NE, improving survival and reducing disability 3 . However, although the severity of cerebral palsy has reduced with HT 4 , survivors have significantly lower cognitive scores which are on average 14 IQ points lower than matched peers even in the absence of cerebral palsy at school-age 5 . Further adjustments to HT protocols do not improve outcome 6,7 , therefore adjunct therapies to augment HT protection are urgently needed.Pre-clinical studies suggest that melatonin (N-acetyl-5-methoxytryptamine) in pharmacologic levels is safe and neuroprotective for hypoxic-ischemic injury in the adult 8 and neonatal 9 brain, mediated by anti-oxidant, anti-apoptotic and anti-inflammatory properties 10,11 . Ex...

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Section: Scientific Reports |mentioning

confidence: 99%

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

Robertson

Lingam

Meehan

et al. 2020

Sci Rep

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“…20,21 In reference to the available literature, 30 to 60% of the patients who suffered severe IVH developed symptomatic PHH, whereas 16 to 25% manage to avoid the implantation of the VPS as the permanent treatment. 1,4 Percentage of patients who managed to avoid the VPS after grade III or IV IVH in our clinic was totaled 34,29%.…”

Section: Discussionmentioning

confidence: 92%

Potential Risk Factors for Ventriculoperitoneal Shunt Implantation in Paediatric Patients with Posthemorrhagic Hydrocephalus of Prematurity Treated with Subcutaneous Reservoir: An Institutional Experience

2021

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Background Posthemorrhagic hydrocephalus of prematurity (PHHP) is a result of intraventricular hemorrhage (IVH). IVH occurs in 6 to 23% of the preterms in countries with advanced medical health care. Most of these patients will eventually require the use of ventriculoperitoneal shunt (VPS). The purpose of this study is to assess the risk factors of VPS implantation in patients with PHHP who have been treated with ventricular catheter with subcutaneous reservoir (VCSR). Methods The retrospective study was conducted evaluating 35 premature patients who suffered from severe IVH. Their mean gestational age was 28 weeks. The assessment included antenatal factors such as gestational age, birth weight, and intrauterine and perinatal infection. Postparturient period factors such as the IVH grade, time between diagnosis, and VCSR implantation and body weight on VCSR implantation were also considered in the study. Postprocedural complications, such as bacterial cerebrospinal fluid (CSF) infection, sepsis, and skin lesions, were evaluated. Data were calculated with R program, version 4.04. Results From among 35 evaluated patients, 23 (65.71%) required a VPS. Median of birth weight was 1,190 g. Infections were observed in 11 (31.43%) cases. Mean time between IVH diagnosis and VCSR implantation was 2.6 weeks. Postprocedural complications occurred in 19 (54.29%) patients. None of the evaluated factors has proven its statistical significance (p > 0.05) for being a potential risk factor for VPS implantation. Conclusion External factors seem to not affect the necessity of VPS implantation in patients after the severe IVH. Ostensibly, there seems to be no difference between the grades III and the IV of Papile's IVH scale regarding VPS implantation necessity.

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“…Recent publications span the spectrum from basic research to clinical trials. [44][45][46][47][48][49] Productive, cutting-edge collaborations are ongoing between clinicians and neuroscientists. The direct, frequent interactions during the weekly Neurosciences Intensive Care Nursery and monthly Pediatric Neurosciences Collaborative fosters interaction across the spectrum from basic, translational, and clinical investigation, with propagation and acceleration of research in every realm.…”

Section: Developmental Neuroscientistsmentioning

confidence: 99%

The Johns Hopkins Neurosciences Intensive Care Nursery Tenth Anniversary (2009-2019): A Historical Reflection and Vision for the Future

Carrasco

Stafstrom

Tekes

et al. 2020

Child Neurology Open

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Since 2009, the Neurosciences Intensive Care Nursery at Johns Hopkins Children’s Center has provided a multidisciplinary approach toward the care of newborns with neurological disorders. The program’s cornerstone is an interdisciplinary approach that involves the primary neonatology team plus experts from more than 10 specialties who convene at a weekly team conference at which newborns with neurological problems are discussed in detail. This interdisciplinary approach fosters in-depth discussion of clinical issues to optimize the management of neonates with neurological problems as well as the opportunity to generate research ideas and provide education about neonatal neuroscience at all levels (faculty, nurses, and trainees). The purpose of this article is to provide a 10-year reflection of our Neurosciences Intensive Care Nursery with a view toward expanding efforts in the 3 areas of our mission: clinical care, research, and education. We hope that our experience will enhance the spread of neonatal neuroscience education, care, and research as widely as possible.

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Extended Combined Neonatal Treatment With Erythropoietin Plus Melatonin Prevents Posthemorrhagic Hydrocephalus of Prematurity in Rats

Cited by 38 publications

References 135 publications

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

Potential Risk Factors for Ventriculoperitoneal Shunt Implantation in Paediatric Patients with Posthemorrhagic Hydrocephalus of Prematurity Treated with Subcutaneous Reservoir: An Institutional Experience

The Johns Hopkins Neurosciences Intensive Care Nursery Tenth Anniversary (2009-2019): A Historical Reflection and Vision for the Future

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