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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the systemic and cerebral effects induced by an increase to 100% of the inspired oxygen fraction (FiO2) on 20 comatose patients with head injury (9 patients) and SAH (11 patients). Brain tissue oxygen tension (PtiO2) was measured through a Clark electrode inserted in penumbra-like areas. We performed 55 hyperoxia tests by increasing FiO2 from 35 +/- 8% to 100% in one second and calculating the PtiO2 index as: PtiO2 variation from baseline at 1 minute/arterial oxygen tension (PaO2) variation from baseline at 1 minute x 100. One hundred percent FiO2 caused an increase of both arterial (from 139 +/- 28 to 396 +/- 77 mmHg) and cerebral (from 22.6 +/- 14 to 65.4 +/- 60 mmHg) oxygenation after 1 minute. The range of the PtiO2 response was not uniform and two groups were identified. The change was small, 0.8 mmHg/min/100 mmHg PaO2 (+/- 0.7; range 0-2) when mean PtiO2 was 19.7 +/- 13.1 mmHg, while a stronger response, 8 mmHg/min/100 mmHg PaO2 (+/- 5; range 3-18) (p < 0.01) was found when mean PtiO2 was 31.7 +/- 14.3 mmHg. Since O2 diffusion should follow the gas diffusion law, the increase in diffusion distance due to a reduction of capillary density in focal lesions may explain this relationship.
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PMID:Effects of hyperoxia on brain tissue oxygen tension in cerebral focal lesions. 1216 35

Stroke causes heterogeneous changes in tissue oxygenation, with a region of decreased blood flow, the penumbra, surrounding a severely damaged ischemic core. Treatment of acute ischemic stroke aims to save this penumbra before its irreversible damage by continued ischemia. However, effective treatment remains elusive due to incomplete understanding of processes leading to penumbral death. While oxygenation is central in ischemic neuronal death, it is unclear exactly what actual changes occur in interstitial oxygen tension (pO2) in ischemic regions during stroke, particularly the penumbra. Using the unique capability of in vivo electron paramagnetic resonance (EPR) oximetry to measure localized interstitial pO2, we measured both absolute values, and temporal changes of pO2 in ischemic penumbra and core during ischemia and reperfusion in a rat model. Ischemia rapidly decreased interstitial pO2 to 32% +/- 7.6% and 4% +/- 0.6% of pre-ischemic values in penumbra and core, respectively 1 hour after ischemia. Importantly, whilst reperfusion restored core pO2 close to its pre-ischemic value, penumbral pO2 only partially recovered. Hyperoxic treatment significantly increased penumbral pO2 during ischemia, but not in the core, and also increased penumbral pO2 during reperfusion. These divergent, important changes in pO2 in penumbra and core were explained by combined differences in cellular oxygen consumption rates and microcirculation conditions. We therefore demonstrate that interstitial pO2 in penumbra and core is differentially affected during ischemia and reperfusion, providing new insights to the pathophysiology of stroke. The results support normobaric hyperoxia as a potential early intervention to save penumbral tissue in acute ischemic stroke.
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PMID:Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats. 1509 Nov 15

Normobaric hyperoxia (NBO) has been shown to extend the reperfusion window after focal cerebral ischemia. Employing diffusion (DWI)- and perfusion (PWI)-weighted magnetic resonance imaging (MRI), the effect of NBO (100% started at 30 mins after middle cerebral artery occlusion (MCAO)) on the spatiotemporal evolution of ischemia during and after permanent (pMCAO) and transient suture middle cerebral artery occlusion (tMCAO) was investigated (experiment 3). In two additional experiments, time window (experiment 1) and cell death pathways (experiment 2) were investigated in the pMCAO model. In experiment 1, NBO treatment reduced infarct volume at 24 h after pMCAO by 10% when administered for 3 h (P>0.05) and by 44% when administered for 6 h (P<0.05). In experiment 2, NBO acutely (390 mins, P<0.05) reduced in situ end labeling (ISEL) positivity in the ipsilesional penumbra but increased contralesional necrotic as well as caspase-3-mediated apoptotic cell death. In experiment 3, CBF characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the apparent diffusion coefficient (ADC)-derived lesion volume essentially stopped progressing during NBO treatment, resulting in a persistent PWI/DWI mismatch that could be salvaged by delayed (3 h) reperfusion. In conclusion, NBO (1) acutely preserved the perfusion/diffusion mismatch without altering CBF, (2) significantly extended the time window for reperfusion, (3) induced lasting neuroprotection in permanent ischemia, and (4) although capable of reducing cell death in hypoperfused tissue it also induced cell death in otherwise unaffected areas. Our data suggest that NBO may represent a promising strategy for acute stroke treatment.
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PMID:Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats. 1731 Oct 78

Normobaric hyperoxia is under investigation as a treatment for acute ischaemic stroke. In experimental models, normobaric hyperoxia reduces cerebral ischaemic injury and improves functional outcome. The mechanisms of neuroprotection are still debated because, (i) inhalation of 100% O2 does not significantly increase total blood O2 content; (ii) it is not known whether normobaric hyperoxia increases O2 delivery to the severely ischaemic cortex because of its short diffusion distance; and (iii) hyperoxia may reduce collateral cerebral blood flow (CBF) to ischaemic penumbra because it can cause vasoconstriction. We addressed these issues using real-time two-dimensional multispectral reflectance imaging and laser speckle flowmetry to simultaneously and non-invasively determine the impact of normobaric hyperoxia on CBF and oxygenation in ischaemic cortex. Ischaemia was induced by distal middle cerebral artery occlusion (dMCAO) in normoxic (30% inhaled O2, arterial pO2 134 +/- 9 mmHg), or hyperoxic mice (100% inhaled O2 starting 15 min after dMCAO, arterial pO2 312 +/- 10 mmHg). Post-ischaemic normobaric hyperoxia caused an immediate and progressive increase in oxyhaemoglobin (oxyHb) concentration, nearly doubling it in ischaemic core within 60 min. In addition, hyperoxia improved CBF so that the area of cortex with < or =20% residual CBF was decreased by 45% 60 min after dMCAO. Furthermore, hyperoxia reduced the frequency of peri-infarct depolarizations (PIDs) by more than 60%, and diminished their deleterious effects on CBF and metabolic load. Consistent with these findings, infarct size was reduced by 45% in the hyperoxia group 2 days after 75 min transient dMCAO. Our data show that normobaric hyperoxia increases tissue O2 delivery, and that novel mechanisms such as CBF augmentation, and suppression of PIDs may afford neuroprotection during hyperoxia.
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PMID:Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia. 1746 17

Spreading depression (SD) is a slowly propagating wave of transient neuronal and glial depolarization that develops after stroke, trauma and subarachnoid hemorrhage. In compromised tissue, repetitive SD-like injury depolarizations reduce tissue viability by worsening the mismatch between blood flow and metabolism. Although the mechanism remains unknown, SDs show delayed electrophysiological recovery within the ischemic penumbra. Here, we tested the hypothesis that the recovery rate of SD can be varied by modulating tissue perfusion pressure and oxygenation. Systemic blood pressure and arterial pO(2) were simultaneously manipulated in anesthetized rats under full physiologic monitoring. We found that arterial hypotension doubled the SD duration, whereas hypertension reduced it by a third compared with normoxic normotensive rats. Hyperoxia failed to shorten the prolonged SD durations in hypotensive rats, despite restoring tissue pO(2). Indeed, varying arterial pO(2) (40 to 400 mm Hg) alone did not significantly influence SD duration, whereas blood pressure (40 to 160 mm Hg) was inversely related to SD duration in compromised tissue. These data suggest that cerebral perfusion pressure is a critical determinant of SD duration independent of tissue oxygenation over a wide range of arterial pO(2) levels, and that hypotension may be detrimental in stroke and subarachnoid hemorrhage, where SD-like injury depolarizations have been observed.
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PMID:Perfusion pressure-dependent recovery of cortical spreading depression is independent of tissue oxygenation over a wide physiologic range. 2008 71

According to the new revised tissue-based definition, transient ischemic attack is a transient episode of neurological dysfunction caused by a focal brain, spinal cord, or retinal ischemia without acute infarction. This review addresses the pathophysiology of transient ischemic attack and the impact of normobaric hyperoxia on the penumbral tissue. Neuroimaging in transient ischemic attack patients and advances in penumbra imaging allow the transient ischemic attack, from pathophysiological viewpoint, to be defined as an ischemic penumbra of varied duration, which could proceed to a cerebral infarction or reduce to a benign oligemia. Persisting perfusion abnormalities are observed, despite resolution of the neurological symptoms. Preclinical and clinical studies have shown that the normobaric hyperoxia treatment is associated with improvement of hemodynamic and metabolic disturbances, particularly in the penumbral tissue. Transient ischemic attack, considered an ischemic penumbra, may present an ideal target for early normobaric hyperoxia therapy, administered as soon as possible after the onset of the neurological deficit. Follow-up perfusion imaging could guide and individualize the treatment.
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PMID:Transient ischemic attack may present a target for normobaric hyperoxia treatment. 2019 87

Oxygen therapy is a promising treatment strategy for ischemic stroke. One potential safety concern with oxygen therapy, however, is the possibility of increased generation of reactive oxygen species (ROS), which could exacerbate ischemic brain injury. Our previous study indicated that normobaric hyperoxia (NBO, 95% O(2) with 5% CO(2)) treatment during ischemia salvaged ischemic brain tissue and significantly reduced ROS generation in transient experimental stroke. In this follow-up study, we tested the hypothesis that suppression of NADPH oxidase is an important mechanism for NBO-induced reduction of ROS generation in focal cerebral ischemia. Male Sprague-Dawley rats were given NBO (95% O(2)) or normoxia (21% O(2)) during 90-min filament occlusion of the middle cerebral artery, followed by 22.5-hour reperfusion. NBO treatment increased the tissue oxygen partial pressure (pO(2)) level in the ischemic penumbra close to the pre-ischemic value, as measured by electronic paramagnetic resonance (EPR), and led to a 30.2% reduction in magnetic resonance imaging (MRI) apparent diffusion coefficients (ADC) lesion volume. Real time PCR and western blot analyses showed that the mRNA and protein expression of NADPH oxidase catalytic subunit gp91(phox) were upregulated in the ischemic brain, which was significantly inhibited by NBO. As a consequence of gp91(phox) inhibition, NBO treatment reduced NADPH oxidase activity in the ischemic brain. Our results suggest that NBO treatment given during ischemia reduces ROS generation via inhibiting NADPH oxidase, which may serve as an important mechanism underlying NBO's neuroprotection in acute ischemic stroke.
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PMID:Inhibition of gp91(phox) contributes towards normobaric hyperoxia afforded neuroprotection in focal cerebral ischemia. 2054 41

Preconditioning-induced ischemic tolerance is one of the most important mechanisms, responsible for the increased brain resistance after stroke. Recent studies over the past years have provided interesting insights into the molecular mechanisms of this neuroprotective phenomenon. In this research, we attempted to see changes in the expression of group I and II metabotropic glutamate receptors (mGluR I and II) following intermittent hyperoxia preconditioning. Rats were divided into five groups (hyperoxia-intact, hyperoxia-MCAO, room air-intact, room air- MCAO, room air-sham). Hyperoxia groups were exposed to 95% inspired O2 for 4 h/day and 6 consecutive days. Oxygen level in room air groups was %21. 48 hours after pretreatment, MCAO-operated groups were subjected to focal cerebral ischemia for 60 min. 24 hours after reperfusion, neurologic deficit score (NDS) and brain infarct volume (IV) were evaluated in MCAO-operated subgroups. Sham-operated and intact groups were used to assess expression of group I and II mGluR and glutathione (GSH) levels of core, penumbra and subcortex regions. The results of this study showed that preconditioning with intermittent HO decreased NDS and IV, increased GSH levels in subcortex, and upregulated mGluRs I and II significantly. Although additional studies will be required to further elucidate precise mechanism(s) of ischemic tolerance, it seems that intermittent HO may exert its protective effects in part through upregulation of mGluR I and II.
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PMID:Ischemic tolerance induced by normobaric hyperoxia and evaluation of group I and II metabotropic glutamate receptors. 2315 Oct 72

Cerebral ischemia interrupts oxygen supply to the affected tissues. Our previous studies have reported that normobaric hyperoxia (NBO) can maintain interstitial partial pressure of oxygen (pO2) in the penumbra of ischemic stroke rats at the physiological level, thus affording significant neuroprotection. However, the mechanisms that are responsible for the penumbra rescue by NBO treatment are not fully understood. Recent studies have shown that zinc, an important mediator of intracellular and intercellular neuronal signaling, accumulates in neurons and leads to ischemic neuronal injury. In this study, we investigate whether NBO could regulate zinc accumulation in the penumbra and prevent mitochondrial damage in penumbral tissue using a transient cerebral ischemic rat model. Our results showed that NBO significantly reduced zinc-staining positive cells and zinc-staining intensity in penumbral tissues, but not in the ischemic core. Moreover, ischemia-induced zinc accumulation in mitochondria, isolated from penumbral tissues, was greatly attenuated by NBO or a zinc-specific chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). NBO or TPEN administration stabilized the mitochondrial membrane potential in the penumbra after cerebral ischemia. Finally, ischemia-induced cytochrome c release from mitochondria in penumbral tissues was significantly reduced by NBO or TPEN treatment. These findings demonstrate a novel mechanism for NBO's neuroprotection, especially to penumbral tissues, providing further evidence for the potential clinical benefit of NBO for acute ischemic stroke.
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PMID:Reduction of zinc accumulation in mitochondria contributes to decreased cerebral ischemic injury by normobaric hyperoxia treatment in an experimental stroke model. 2589 41

In order to protect the brain before an irreversible injury occurs, penumbral oxygenation is the primary goal of current acute ischemic stroke treatment. However, hyperoxia treatment remains controversial due to the risk of free radical generation and vasoconstriction. Melatonin is a highly potent free radical scavenger that protects against ischemic stroke. Considering its anti-oxidant activity, we hypothesized that melatonin may augment the survival-promoting action of normobaric oxygen (NBO) and prevent brain infarction. Herein, we exposed mice to 30 or 90 min of intraluminal middle cerebral artery occlusion (MCAo) and evaluated the effects of NBO (70% or 100% over 90 min), administered either alone or in combination with melatonin (4 mg/kg, i.p.), on disseminate neuronal injury, neurological deficits, infarct volume, blood-brain barrier (BBB) permeability, cerebral blood flow (CBF) and cell signaling. Both NBO and particularly melatonin alone reduced neuronal injury, neurological deficits, infarct volume and BBB permeability, and increased post-ischemic CBF, evaluated by laser speckle imaging (LSI). They also improved CBF significantly in the ischemic- core and penumbra, which was associated with reduced IgG extravasation, DNA fragmentation, infarct volume, brain swelling and neurological scores. Levels of phosphorylated Akt, anti-apoptotic Bcl-xL, pro-apoptotic Bax and endothelial nitric oxide synthase (NOS) were re-regulated after combined oxygen and melatonin delivery, whereas neuronal and inducible NOS, which were increased by oxygen treatment, were not influenced by melatonin. Our present data suggest that melatonin and NBO are promising approaches for the treatment of acute-ischemic stroke, which encourage proof-of-concept studies in human stroke patients.
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PMID:Effects of normobaric oxygen and melatonin on reperfusion injury: role of cerebral microcirculation. 2641 28


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