Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In neonates asphyxia is usually followed by hyperoxia due to resuscitation procedures. In order to study whether hyperoxic reoxygenation might cause additional cell injury we subjected organotypic hippocampal slice cultures of juvenile rats to normoxic or hyperoxic reoxygenation (19 or 85% oxygen, respectively) following hypoxia (3% oxygen) for 30, 60, and 120 min. Cell injury was quantified by lactate dehydrogenase (LDH) release and propidium iodide (PI) fluorescence 1 h after end of the reoxygenation period. In both experimental groups, LDH activity was significantly enhanced by hypoxia as compared to normoxic controls. However, hyperoxic reoxygenation caused a larger increase in LDH activity than normoxic reoxygenation (e.g., by a factor of 1.60 vs. 1.29 following 120 min hypoxia). PI fluorescence increased after hypoxia in all principal cell layers of the hippocampus but again showed a larger enhancement after hyperoxic reoxygenation as compared to normoxic reoxygenation (e.g., by a factor of 3.9 vs. 1.7 for CA1 and 120 min of hypoxia). After normoxic reoxygenation, PI fluorescence intensity was lower in the dentate gyrus as compared to CA1 and CA3, while it reached similar values like CA1 after high oxygen supply. In conclusion, juvenile hippocampal slice cultures subjected to hyperoxic reoxygenation display a greater amount of acute neuronal injury than slice cultures undergoing normoxic reoxygenation.
 ...
PMID:Acute neuronal injury after hypoxia is influenced by the reoxygenation mode in juvenile hippocampal slice cultures. 1212 52

Resuscitation with 100% ventilatory oxygen is routinely initiated after severe traumatic brain injury (TBI). Despite the objective to improve oxygenation of the injured brain, there are concerns about the increased production of reactive oxygen species (ROS), which can lead to further neuronal damage. 3-nitrotyrosine (3-NT), the product of peroxynitrite-meditated tyrosine residue nitration, has been used as a marker for ROS-induced oxidative damage to proteins. We hypothesized that posttraumatic resuscitation with hyperoxic ventilation with a fraction of inspired oxygen (Fio2, 100%) results in increased ROS-induced damage to proteins compared with resuscitation with normoxic ventilation or room air (Fio2, 21%). Male Sprague-Dawley rats underwent controlled cortical impact (CCI) and were resuscitated with either normoxic or hyperoxic ventilation for 1 hour after injury (n = 5 per group). Sham-operated control groups received 1 hour of normoxic or hyperoxic ventilation without CCI (n = 4-5 per group). Twenty-four hours after injury, rats were perfused with fixative, and hippocampi were evaluated for levels of 3-NT immunostaining. In a second experiment, for a delayed assessment of neuronal survival, another set of rats similarly underwent CCI and normoxic or hyperoxic ventilation for 1 hour (n = 4 per group), and a sham-operated group was used as a control (n = 4). One week after injury, neuronal cell counts and abnormal cell quantification were performed after staining with the neuron-specific NeuN antibody. Quantification of 3-NT staining revealed significantly increased levels in the ipsilateral hippocampus in the hyperoxic CCI group. The normoxic group showed a 51.0% reduction of staining in CA1 when compared with those rats resuscitated with hyperoxia and a 50.8% reduction in CA3 (both P < 0.05). There was no significant difference in staining between the injured normoxic group and the sham-operated groups. In the delayed analysis of neuronal survival, although neuronal counts were reduced in the hippocampus on the injured side in both injured groups, there was no significant difference between hyperoxic and normoxic groups. Similarly, abnormal cell counts were not significantly different between groups.
 ...
PMID:Synthes Award for Resident Research on Brain and Craniofacial Injury: normoxic ventilatory resuscitation after controlled cortical impact reduces peroxynitrite-mediated protein nitration in the hippocampus. 1662 92

Extremely premature infants are often exposed to supra-physiologic concentrations of oxygen, and frequently have hypoxemic episodes. These preterm infants are at high risk (~40%) for neurodevelopmental impairment (NDI) even in the absence of obvious intracranial pathology such as intraventricular hemorrhage or periventricular leukomalacia. The etiology for NDI has not been determined, and there are no animal models to simulate neurodevelopmental outcomes of prematurity. Our objectives were to develop and characterize a mouse model to determine long-term effects of chronic hypoxia or hyperoxia exposure on neurodevelopment. Newborn C57BL/6 mice were exposed to hypoxia (12% O(2)) or hyperoxia (85% O(2)) from postnatal days 1 to 14 and then returned to air. At 12-14 weeks of age, neurobehavioral assessment (Water Maze test, Novel Object Recognition test, Open Field test, Elevated Plus Maze, and Rotarod test) was performed, followed by MRI and brain histology. Neurobehavioral testing revealed that hyperoxia-exposed mice did poorly on the water maze and novel object recognition tests compared to air-exposed mice. MRI demonstrated smaller hippocampi in hyperoxia- and hypoxia-exposed mice with a greater reduction in hyperoxia-exposed mice, including a smaller cerebellum in hyperoxia-exposed mice. Brain histology showed reduced CA1 and CA3 and increased dentate gyral width in hippocampus. In conclusion, neonatal hyperoxia in mice leads to abnormal neurobehavior, primarily deficits in spatial and recognition memory, associated with smaller hippocampal sizes, similar to findings in ex-preterm infants. This animal model may be useful to determine mechanisms underlying developmental programming of NDI in preterm infants, and for evaluation of therapeutic strategies.
 ...
PMID:Neurodevelopmental impairment following neonatal hyperoxia in the mouse. 2306 37