Hyperoxia with 100% Oxygen following Hypoxia-Ischemia Increases Brain Damage in Newborn Rats

Shimabuku, Roberto; Ota, Arturo; Pereyra, Sonia; Véliz, Betty; Paz, Edith; Nakachi, Graciela; More, Mario; Oliveros, Miguel

doi:10.1159/000086206

Cited by 33 publications

(20 citation statements)

References 30 publications

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“…Several groups have found increased brain lesions in neonatal rats after hyperoxic reoxygenation following HI (25,38,39). The increased inflammatory gene response after hyperoxic reoxygenation we found in the present study, supports the evidence that increased inflammation might be one of the contributing factors to the increased brain damage after hyperoxic reoxygenation.…”

Section: Igf1rsupporting

confidence: 91%

Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation

et al. 2014

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Background: Hyperoxic reoxygenation following hypoxia increases the expression of inflammatory genes in the neonatal mouse brain. We have therefore compared the temporal profile of 44 a priori selected genes after hypoxia and hyperoxic or normoxic reoxygenation. Methods: Postnatal day 7 mice were subjected to 2 h of hypoxia (8% O 2 ) and 30 min reoxygenation with 60% or 21% O 2 . After 0 to 72 h observation, mRNA and protein were examined in the hippocampus and striatum. results: There were significantly higher gene expression changes in six genes after hyperoxic compared to normoxic reoxygenation. Three genes had a generally higher expression throughout the observation period: the inflammatory genes Hmox1 (mean difference: 0.52, 95% confidence interval (CI): 0.15-1.01) and Tgfb1 (mean difference: 0.099, CI: 0.003-0.194), and the transcription factor Nfkb1 (mean difference: 0.049, CI: 0.011-0.087). The inflammatory genes Cxcl10 and Il1b, and the DNA repair gene Neil3, had a higher gene expression change after hyperoxic reoxygenation at one time point only. Nineteen genes involved in inflammation, transcription regulation, apoptosis, angiogenesis, and glucose transport had significantly different gene expression changes with time in all intervention animals. conclusion: We confirm that hyperoxic reoxygenation induces a stronger inflammatory gene response than reoxygenation with air.

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Section: Igf1rsupporting

confidence: 91%

Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation

et al. 2014

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“…The volume of the hyperintense lesions after HHI was significantly larger compared to HI alone (3 weeks PI, Fig. 2) similarly to results reported elsewhere for one day post-injury (Gill et al, 2008) that showed larger cortical damage than previous reports (Shimabuku et al, 2005) where there was brain damage in 42% of rats treated with HHI and 13% of those treated with HI. We report that HI caused lesions in 60% of rats and HHI caused lesions in 100% of all rats.…”

Section: Injury After Hhisupporting

confidence: 89%

“…A guideline for the treatment of acute perinatal hypoxia is resuscitation with 100% oxygen (hyperoximia) (Niermeyer et al, 2000). It has been reported that in experimental perinatal hypoxia, acute hyperoximic treatment exacerbates the initial injury (Munkeby et al, 2004;Shimabuku et al, 2005). Hu et al (2003) reported that hyperoximia in rats triggers an additional apoptotic signaling pathway when compared to hypoxia alone.…”

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confidence: 99%

Normobaric hyperoximia increases hypoxia‐induced cerebral injury: DTI study in rats

Bockhorst

Narayana

Dulin

et al. 2009

J of Neuroscience Research

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Perinatal hypoxia affects normal neurological development and can lead to motor, behavioral and cognitive deficits. A common acute treatment for perinatal hypoxia is oxygen resuscitation (hyperoximia), a controversial treatment. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), was performed in a P7 rat model of perinatal hypoxia to determine the effect of hyperoximia. These studies were performed on two groups of animals: 1) animals which were subjected to ischemia followed by hypoxia (HI), and 2) HI followed by hyperoximic treatment (HHI). Lesion volumes on high resolution MRI and DTI derived measures, fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusivities (lambda(l) and lambda(t), respectively) were measured in vivo one day, one week, and three weeks after injury. Most significant differences in the MRI and DTI measures were found at three weeks after injury. Specifically, three weeks after HHI injury resulted in significantly larger hyperintense lesion volumes (95.26 +/- 50.42 mm(3)) compared to HI (22.25 +/- 17.62 mm(3)). The radial diffusivity lambda(t) of the genu of corpus callosum was significantly larger in HHI (681 +/- 330 x 10(-6) mm(2)/sec) than in HI (486 +/- 96 x 10(-6) mm(2)/sec). Over all, most significant differences in all the DTI metrics (FA, MD, lambda(t), lambda(l)) at all time points were found in the corpus callosum. Our results suggest that treatment of perinatal hypoxia with normobaric oxygen does not ameliorate, but exacerbates damage.

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“…Similarly, in other studies, the duration of postischemic reoxygenation with use of pure oxygen varies from 5 min to 24 h regardless of the resuscitation-induced changes in CBF (4,5,25). This may limit the clinical value of experimental data.…”

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confidence: 95%

“…Perhaps, significantly worse geotaxis reflex performance in Re-O 2 mice is related to this pathophysiological sequence. Physiologically unjustified, prolonged (24 h) use of pure O 2 after restoration of O 2 tissue delivery has been shown to adversely affect postHI recovery in neonatal rats (25).…”

mentioning

confidence: 99%

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

et al. 2006

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Study investigated neuroutcome in mice subjected at 7-8 d of life to hypoxic-ischemic brain injury (HI) followed by 30 min of reoxygenation with 100% O 2 (Re-O 2 ) or room air (Re-Air). At 24 h of recovery, mouse reflexes were tested. At 7 wks after HI spatial orientation and memory were assessed in the same mice. Mortality rate was recorded at 24 h and at 7 wks of recovery. In separate cohort of mice, changes in cerebral blood flow (CBF) during HI-insult and reoxygenation were recorded. T he resuscitation of asphyxiated neonates is aimed to reestablish tissue oxygen delivery by restoring blood flow and increasing the arterial oxygen content. Use of 100% O 2 during neonatal resuscitation is currently recommended (1). However, Re-O 2 compared with Re-Air significantly exacerbates an oxidative stress in asphyxiated neonates (2), which is one of the mechanisms of HI-brain injury (3). To avoid hyperoxia-induced oxidative stress, the efficacy of resuscitation with room air (RA) instead of 100% O 2 is being extensively studied. To date, results of these studies are conflicting. For instance, it was reported that in asphyxiated pigs the Re-O 2 restored CBF significantly faster and more complete compared with Re-Air (4). Significantly higher levels of excitatory amino acids were found in the striatum of newborn HI-piglets Re-Air compared with Re-O 2 piglets which may be indicative of less favorable neurologic prognosis for Re-Air animals (5). However, Liu. Y and co-authors, using a canine model of cardiac arrest, demonstrated that Re-O 2 versus ReAir resulted in greater neurologic impairment assessed at 24 h of recovery (6). In contrast, the postischemic use of hyperbaric oxygenation, which produces substantial oxidative stress (7), significantly improved neurologic score following focal cerebral ischemia in adult rats and HI in neonatal rats (8,9). Hyperbaric oxygenation used as a mode of resuscitation from experimental heatstroke in rats was shown to be significantly neuroprotective (10). Meier and co-authors reported that hyperoxic ventilation significantly reduced short-term (6 h) mortality due to systemic ischemia following an acute hemorrhagic shock in pigs (11). The most recent meta-analysis indicates that there are not enough data to challenge current recommendation of using of pure O 2 during resuscitation (12).The assessment of long-term neurologic handicap following HI is of paramount clinical value to define the ultimate efficacy of Re-O2 versus Re-Air in an asphyxiated subject. There are no reports on late neurologic outcome and reoxygenation strategy following asphyxia. This work was undertaken to provide experimental data on short-and long-term neuropathological and neurofunctional outcomes in HIaffected mice re-oxygenated with either 100% O 2 or RA immediately following the index event. MATERIALS AND METHODSMurine model of HI. Three day old (p3) C57/BL6J mice of both genders were purchased from Jackson Laboratories (Bar Harbor, ME) with their birth mothers. All research was conducted according ...

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Hyperoxia with 100% Oxygen following Hypoxia-Ischemia Increases Brain Damage in Newborn Rats

Cited by 33 publications

References 30 publications

Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation

Increased expression of inflammatory genes in the neonatal mouse brain after hyperoxic reoxygenation

Normobaric hyperoximia increases hypoxia‐induced cerebral injury: DTI study in rats

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

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