scholarly journals Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Eridan Rocha-Ferreira ◽  
Brogan Rudge ◽  
Michael P. Hughes ◽  
Ahad A. Rahim ◽  
Mariya Hristova ◽  
...  
Keyword(s):  
Brain Injury ◽  
Beneficial Effect ◽  
Nitrosative Stress ◽  
Birth Asphyxia ◽  
Treated Group ◽  
Ischemic Postconditioning ◽  
Perinatal Hypoxia ◽  
Enos Expression ◽  
Remote Ischemic Postconditioning ◽  
Hypoxia Ischemia

Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention that could be administered as an alternative to cooling in cases of perinatal hypoxia-ischemia (HI). In the current study we hypothesized that RIPostC in the piglet model of birth asphyxia confers protection by reducing nitrosative stress and subsequent nitrotyrosine formation, as well as having an effect on glial immunoreactivity. Postnatal day 1 (P1) piglets underwent HI brain injury and were randomised to HI (control) or HI + RIPostC. Immunohistochemistry assessment 48 hours after HI revealed a significant decrease in brain nitrotyrosine deposits in the RIPostC-treated group (p=0.02). This was accompanied by a significant increase in eNOS expression (p<0.0001) and decrease in iNOS (p=0.010), with no alteration in nNOS activity. Interestingly, RIPostC treatment was associated with a significant increase in GFAP (p=0.002) and IBA1 (p=0.006), markers of astroglial and microglial activity, respectively. The current study demonstrates a beneficial effect of RIPostC therapy in the preclinical piglet model of neonatal asphyxia, which appears to be mediated by modulation of nitrosative stress, despite glial activation.

Short-term outcomes of remote ischemic postconditioning 1 h after perinatal hypoxia–ischemia in term piglets

2020 ◽  
Author(s):  
Kasper J. Kyng ◽  
Sigrid Kerrn-Jespersen ◽  
Kristine Bennedsgaard ◽  
Torjus Skajaa ◽  
Michael Pedersen ◽  
...  
Keyword(s):  
Ischemic Postconditioning ◽  
Perinatal Hypoxia ◽  
Short Term ◽  
Remote Ischemic Postconditioning ◽  
Hypoxia Ischemia

scholarly journals Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter

2015 ◽  
Vol 36 (8) ◽  
pp. 1396-1411 ◽  
Author(s):  
Mojgan Ezzati ◽  
Alan Bainbridge ◽  
Kevin D Broad ◽  
Go Kawano ◽  
Aaron Oliver-Taylor ◽  
...  
Keyword(s):  
White Matter ◽  
Corpus Callosum ◽  
Grey Matter ◽  
Ischemia Reperfusion ◽  
Ischemic Postconditioning ◽  
White Female ◽  
Resonance Spectroscopy ◽  
Periventricular White Matter ◽  
Remote Ischemic Postconditioning ◽  
Hypoxia Ischemia

Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention ( n = 8); (ii) RIPostC – with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI ( n = 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate ( p = 0.005) and increased whole brain phosphorus-31 MRS ATP ( p = 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter ( p = 0.03), internal capsule ( p = 0.002) and corpus callosum ( p = 0.021); there was reduced microglial activation in corpus callosum ( p = 0.001) and more surviving oligodendrocytes in corpus callosum ( p = 0.029) and periventricular white matter ( p = 0.001). Changes in gene expression were detected in the white matter at 48 h, including KATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter.

scholarly journals Perinatal hypoxic-ischemic brain injury in large animal models: Relevance to human neonatal encephalopathy

2018 ◽  
Vol 38 (12) ◽  
pp. 2092-2111 ◽  
Author(s):  
Raymond C Koehler ◽  
Zeng-Jin Yang ◽  
Jennifer K Lee ◽  
Lee J Martin
Keyword(s):  
Brain Injury ◽  
Animal Models ◽  
Cerebral Hypoperfusion ◽  
Large Animal ◽  
Perinatal Hypoxia ◽  
Cellular Mechanisms ◽  
Fetal Sheep ◽  
Newborn Piglets ◽  
Large Animal Models ◽  
Hypoxia Ischemia

Perinatal hypoxia-ischemia resulting in death or lifelong disabilities remains a major clinical disorder. Neonatal models of hypoxia-ischemia in rodents have enhanced our understanding of cellular mechanisms of neural injury in developing brain, but have limitations in simulating the range, accuracy, and physiology of clinical hypoxia-ischemia and the relevant systems neuropathology that contribute to the human brain injury pattern. Large animal models of perinatal hypoxia-ischemia, such as partial or complete asphyxia at the time of delivery of fetal monkeys, umbilical cord occlusion and cerebral hypoperfusion at different stages of gestation in fetal sheep, and severe hypoxia and hypoperfusion in newborn piglets, have largely overcome these limitations. In monkey, complete asphyxia produces preferential injury to cerebellum and primary sensory nuclei in brainstem and thalamus, whereas partial asphyxia produces preferential injury to somatosensory and motor cortex, basal ganglia, and thalamus. Mid-gestational fetal sheep provide a valuable model for studying vulnerability of progenitor oligodendrocytes. Hypoxia followed by asphyxia in newborn piglets replicates the systems injury seen in term newborns. Efficacy of post-insult hypothermia in animal models led to the success of clinical trials in term human neonates. Large animal models are now being used to explore adjunct therapy to augment hypothermic neuroprotection.

Perinatal Hypoxia-Ischemia and Brain Injury

2000 ◽  
Vol 47 (4) ◽  
pp. 431-432 ◽  
Author(s):  
A D Edwards ◽  
D V Azzopardi
Keyword(s):  
Brain Injury ◽  
Perinatal Hypoxia ◽  
Hypoxia Ischemia

scholarly journals Nutraceuticals in the Prevention of Neonatal Hypoxia–Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions

2021 ◽  
Vol 22 (5) ◽  
pp. 2524
Author(s):  
Marta Reyes-Corral ◽  
Noelia Sola-Idígora ◽  
Rocío de la Puerta ◽  
Joan Montaner ◽  
Patricia Ybot-González
Keyword(s):  
Brain Injury ◽  
Birth Asphyxia ◽  
Blood Perfusion ◽  
In Vivo Studies ◽  
Omega 3 ◽  
Mortality And Morbidity ◽  
Nutritional Interventions ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

Neonatal hypoxia–ischemia (HI) is a brain injury caused by oxygen deprivation to the brain due to birth asphyxia or reduced cerebral blood perfusion, and it often leads to lifelong limiting sequelae such as cerebral palsy, seizures, or mental retardation. HI remains one of the leading causes of neonatal mortality and morbidity worldwide, and current therapies are limited. Hypothermia has been successful in reducing mortality and some disabilities, but it is only applied to a subset of newborns that meet strict inclusion criteria. Given the unpredictable nature of the obstetric complications that contribute to neonatal HI, prophylactic treatments that prevent, rather than rescue, HI brain injury are emerging as a therapeutic alternative. Nutraceuticals are natural compounds present in the diet or used as dietary supplements that have antioxidant, anti-inflammatory, or antiapoptotic properties. This review summarizes the preclinical in vivo studies, mostly conducted on rodent models, that have investigated the neuroprotective properties of nutraceuticals in preventing and reducing HI-induced brain damage and cognitive impairments. The natural products reviewed include polyphenols, omega-3 fatty acids, vitamins, plant-derived compounds (tanshinones, sulforaphane, and capsaicin), and endogenous compounds (melatonin, carnitine, creatine, and lactate). These nutraceuticals were administered before the damage occurred, either to the mothers as a dietary supplement during pregnancy and/or lactation or to the pups prior to HI induction. To date, very few of these nutritional interventions have been investigated in humans, but we refer to those that have been successful in reducing ischemic stroke in adults. Overall, there is a robust body of preclinical evidence that supports the neuroprotective properties of nutraceuticals, and these may represent a safe and inexpensive nutritional strategy for the prevention of neonatal HI encephalopathy.

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