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Abstract Background Anemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries. Methods This is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann–Whitney tests, and linear and logistic regression. Results The final analysis included 33 patients (median age 62 [IQR 58–66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3–57.8) versus − 5.3% (IQR − 19.2–57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines’ values. Conclusions This study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings. Trial registration The study was retrospectively registered under NCT number 06321874 on The 10th of April 2024.

Background: Anemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries. Methods: This is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann–Whitney tests, and linear and logistic regression. Results: The final analysis included 33 patients (median age 62 [IQR 58–66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3–57.8) versus − 5.3% (IQR − 19.2–57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines’ values. Conclusions: This study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings. Trial registration: The study was retrospectively registered under NCT number 06321874 on The 10th of April 2024. [ABSTRACT FROM AUTHOR]

Background: Stroke, including ischemic and hemorrhagic stroke, is a severe and prevalent acute cerebrovascular disease. The development of hypoxia following stroke can trigger a cascade of pathological events, including mitochondrial dysfunction, energy deficiency, oxidative stress, neuroinflammation, and excitotoxicity, all of which are often associated with unfavorable prognosis. Nonetheless, a noninvasive intervention, referred to as normobaric hyperoxia (NBO), is known to have neuroprotective effects against stroke. Results: NBO can exert neuroprotective effects through various mechanisms, such as the rescue of hypoxic tissues, preservation of the blood–brain barrier, reduction of brain edema, alleviation of neuroinflammation, improvement of mitochondrial function, mitigation of oxidative stress, reduction of excitotoxicity, and inhibition of apoptosis. These mechanisms may help improve the prognosis of stroke patients. Conclusions: This review summarizes the mechanism by which hypoxia causes brain injury and how NBO can act as a neuroprotective therapy to treat stroke. We conclude that NBO has significant potential for treating stroke and may represent a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

Normobaric hyperoxia (NBO) is a potentially promising stroke treatment strategy that could protect the ischemic penumbra and could be administered as an adjunct before vascular recanalization. However, the efficacy and safety of NBO have not been confirmed by randomized controlled trials. The study aims to assess the efficacy and safety of NBO for ischemic stroke due to large artery occlusion (LVO) of acute anterior circulation among patients who had endovascular treatment (EVT) and were randomized within 6 h from symptom onset. Based on the data of the modified Rankin Scale (mRS) score at 90 days from the normobaric hyperoxia combined with EVT for acute ischemic stroke (OPENS: NCT03620370) trial, 284 patients will be included to achieve a 90% power by using Wilcoxon-Mann-Whitney test and the proportional odds model to calculate the sample size. The study is a prospective, multicenter, blinded, randomized controlled trial. The NBO group is administered with mask oxygen therapy of 10 L/min, while the sham NBO group is with that of 1 L/min. The primary outcome is the mRS score at 90 days. Secondary endpoints include cerebral infarct volume at 24–48 h, functional independence (mRS ≤2) at 90 days, and improvement in neurological function at 24 h. Safety outcomes include 90-day mortality, oxygen-related adverse events, and serious adverse events. This study will indicate whether NBO combined with EVT is superior to EVT alone for acute ischemic stroke caused by LVO in subjects randomized within 6 h from symptom onset and will provide some evidence for NBO intervention as an adjunct to thrombectomy for acute stroke. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease, and the complement cascade exacerbates brain injury after ICH. As the most abundant component of the complement system, complement component 3 (C3) plays essential roles in all three complement pathways. However, the effects of C3 on neurological impairment and brain injury in ICH patients and the related mechanism have not been fully elucidated. Normobaric hyperoxia (NBO) is regarded as a treatment for ICH patients, and recent clinical studies also have confirmed the neuroprotective role of NBO against acute ICH‐mediated brain damage, but the underlying mechanism still remains elusive. Aims: In the present study, we investigated the effects of complement C3 on NBO‐treated ICH patients and model mice, and the underlying mechanism of NBO therapy in ICH‐mediated brain injury. Results: Hemorrhagic injury resulted in the high plasma C3 levels in ICH patients, and the plasma C3 levels were closely related to hemorrhagic severity and clinical outcomes after ICH. BO treatment alleviated neurologic impairments and rescued the hemorrhagic‐induced increase in plasma C3 levels in ICH patients and model mice. Moreover, the results indicated that NBO exerted its protective effects of on brain injury after ICH by downregulating the expression of C3 in microglia and alleviating microglia‐mediated synaptic pruning. Conclusions: Our results revealed that NBO exerts its neuroprotective effects by reducing C3‐mediated synaptic pruning, which suggested that NBO therapy could be used for the clinical treatment of ICH. [ABSTRACT FROM AUTHOR]

Background: Gentamicin (GM) induced nephrotoxicity is one of the most common causes of acute kidney injury and limits its administration. Evidence suggests that pre-treatment with oxygen increases the activity of antioxidant enzymes and protects tissues against different kinds of damage. In this study, the effect of daily normobaric heperoxia pre-treatment on alleviating gentamicin induced nephrotoxicity was investigated. Materials and Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): Control (room air); Gentamicin (100 mg/kg, IP, for 9 days); Hyperoxia60 (60 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days) and Hyperoxia180 (180 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days). Then 24 h urine was collected and on day 10, the rats were sacrificed for serum, urine and renal tissue sampling. Results: Results showed that hyperoxia significantly enhanced renal antioxidative capacity and decreased serum creatinine and renal failure index. Histological examination and SPECT scan also showed that tissue damage in the hyperoxia groups was lower compared to the gentamicin group. However, hyperoxia effect on body weight, kidney-to-body weight ratio, urine volume, blood urea nitrogen and glomerular filtration was not significant. Conclusion: Although pre-treatment with hyperoxia enhances the antioxidant capacity of renal tissue and improves some of the functional and histopathological parameters of the kidney, it failed to completely restore the adverse effects of gentamicin-induced nephrotoxicity. Thus, more studies are needed to determine the clinical effect of hyperoxia on gentamicin-induced nephrotoxicity.

Background: Ischemic stroke is one of the most severe cerebrovascular diseases that leads to disability and death and seriously endangers health and quality of life. Insufficient oxygen supply is a critical factor leading to ischemic brain injury. However, effective therapies for ischemic stroke are lacking. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve prognosis after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBHO) has been shown to have neuroprotective effects during ischemic stroke and is considered an appropriate neuroprotective therapy for ischemic stroke. Evidence indicates that NBHO plays a neuroprotective role through different mechanisms in acute ischemic stroke. Recent studies have also reported that combinations with other drug therapies can enhance the efficacy of NBHO in ischemic stroke. Here, we aimed to provide a summary of the potential mechanisms underlying the use of NBHO in ischemic stroke and an overview of the benefits of NBHO in ischemic stroke. Methods: We screened 83 articles on PubMed and other websites. A quick review was conducted, including clinical trials, animal trials, and reviews of studies in the field of NBHO treatment published before July 1, 2023. The results were described and synthesized, and the bias risk and evidence quality of all included studies were assessed. Results: The results were divided into four categories: the mechanism of NBHO, animal and clinical trials of NBHO, the clinical application and prospects of NBHO, and adverse reactions of NBHO. Conclusion: NBHO is a simple, non-invasive therapy that may be delivered early after stroke onset, with promising potential for the treatment of acute ischemic stroke. However, the optimal therapeutic regimen remains uncertain. Further studies are needed to confirm its efficacy and safety.

Acute ischemic stroke (AIS) is a serious neurological disease. Normobaric hyperoxia (NBHO) is both a non-invasive and easy method that seems to be able to improve outcomes after cerebral ischemia/reperfusion. In clinical trials, normal low-flow oxygen has been shown to be ineffective, but NBHO has been shown to have a transient brain-protective effect. Today, NBHO combined with recanalization is the best treatment available. NBHO combined with thrombolysis is considered to improve neurological scores and long-term outcomes. Large randomized controlled trials (RCTs), however, are still needed to determine the role they will have in stroke treatment. RCTs of NBHO combined with thrombectomy have both improved infarct volume at 24 hours and the long-term prognosis. These two mechanisms most likely play key roles in the neuroprotective actions of NBHO after recanalization, including the increase in penumbra oxygen supply and the integrity of the blood-brain barrier (BBB). Considering the mechanism of action of NBHO, oxygen should be given as early as possible to increase the duration of oxygen therapy before recanalization is initiated. NBHO can further prolong the existence time of penumbra, so that more patients may benefit from it. Overall, however, recanalization therapy is still essential. [ABSTRACT FROM AUTHOR]

Background: Gentamicin (GM) induced nephrotoxicity is one of the most common causes of acute kidney injury and limits its administration. Evidence suggests that pre-treatment with oxygen increases the activity of antioxidant enzymes and protects tissues against different kinds of damage. In this study, the effect of daily normobaric heperoxia pre-treatment on alleviating gentamicin induced nephrotoxicity was investigated. Materials and Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): Control (room air); Gentamicin (100 mg/kg, IP, for 9 days); Hyperoxia60 (60 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days) and Hyperoxia180 (180 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days). Then 24 h urine was collected and on day 10, the rats were sacrificed for serum, urine and renal tissue sampling. Results: Results showed that hyperoxia significantly enhanced renal antioxidative capacity and decreased serum creatinine and renal failure index. Histological examination and SPECT scan also showed that tissue damage in the hyperoxia groups was lower compared to the gentamicin group. However, hyperoxia effect on body weight, kidney-to-body weight ratio, urine volume, blood urea nitrogen and glomerular filtration was not significant. Conclusion: Although pre-treatment with hyperoxia enhances the antioxidant capacity of renal tissue and improves some of the functional and histopathological parameters of the kidney, it failed to completely restore the adverse effects of gentamicin-induced nephrotoxicity. Thus, more studies are needed to deter- mine the clinical effect of hyperoxia on gentamicin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Background: Gentamicin (GM) induced nephrotoxicity is one of the most common causes of acute kidney injury and limits its administration. Evidence suggests that pre-treatment with oxygen increases the activity of antioxidant enzymes and protects tissues against different kinds of damage. In this study, the effect of daily normobaric heperoxia pre-treatment on alleviating gentamicin induced nephrotoxicity was investigated. Materials and Methods: Twenty-eight male Wistar rats were randomly divided into four groups (n=7): Control (room air); Gentamicin (100 mg/kg, IP, for 9 days); Hyperoxia60 (60 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days) and Hyperoxia180 (180 min daily pretreatment with 95% oxygen and then 100 mg/kg gentamicin, IP, for 9 days). Then 24 h urine was collected and on day 10, the rats were sacrificed for serum, urine and renal tissue sampling. Results: Results showed that hyperoxia significantly enhanced renal antioxidative capacity and decreased serum creatinine and renal failure index. Histological examination and SPECT scan also showed that tissue damage in the hyperoxia groups was lower compared to the gentamicin group. However, hyperoxia effect on body weight, kidney-to-body weight ratio, urine volume, blood urea nitrogen and glomerular filtration was not significant. Conclusion: Although pre-treatment with hyperoxia enhances the antioxidant capacity of renal tissue and improves some of the functional and histopathological parameters of the kidney, it failed to completely restore the adverse effects of gentamicin-induced nephrotoxicity. Thus, more studies are needed to determine the clinical effect of hyperoxia on gentamicin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: Acute cerebral ischemia is caused by an insufficient blood supply to brain tissue. Oxygen therapy, which is able to aid diffusion to reach the ischemic region, has been regarded as a possible treatment for cerebral ischemia. Recent animal and pilot clinical studies have reported that normobaric hyperoxia (NBO) showed neuroprotective effects if started soon after the onset of stroke. However, little is known about the role and mechanism of NBO treatment in astrocytes. Connexin43, one of the main gap junction proteins in astrocytes, is extremely sensitive to hypoxia and oxidative stress after cerebral ischemia. Aims: In the present study, we used sutures to develop an ischemia/reperfusion model in rats to mimic clinical recanalization and investigated the role of connexin43 in NBO‐treated stroke rats, as well as the underlying mechanism of NBO therapy. Results: Normobaric hyperoxia treatment maintained the homeostasis of oxidoreductases: glutathione peroxidase 4 (GPX4) and NADPH oxidase 4 (two important oxidoreductases) and rescued the ischemia/reperfusion‐induced downregulation of connexin43 protein in astrocytes. Furthermore, NBO treatment attenuated cerebral ischemia‐induced cytochrome c release from mitochondria and was involved in neuroprotective effects by regulating the GPX4 and connexin43 pathway, using Ferrostatin‐1 (an activator of GPX4) or Gap27 (an inhibitor of connexin43). Conclusions: This study showed the neuroprotective effects of NBO treatment by reducing oxidative stress and maintaining the level of connexin43 in astrocytes, which could be used for the clinical treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance is a substantial obstacle in cancer therapy. The microenvironment of solid tumor growth can be hypoxic, which promotes the survival, growth, and progression of cancer cells and reduces the effects of chemotherapy and radiotherapy. Hyperoxia treatment has potential to enhance cancer therapies. Objective: We evaluated whether normobaric hyperoxia (NBO) therapy has an anticancer effect and can be a strategy for overcoming anticancer drug resistance. Human alveolar adenocarcinoma (A549) and paclitaxel (PTX)-resistant (A549/PR) cell lines were used. Cells were assessed after exposure to room air (RA) or NBO for 48 h with and without PTX application. Results: NBO exposure inhibited cell viability, migration abilities, and proliferation in both cell lines. Chemo-resistant cell lines have shown variable viability upon NBO exposure. NBO exposure induced critical cytotoxicity and attenuated the characteristics of cancer in A549/PR cells. NBO induced a decline of chemoresistance in A549/PR cells when co-treated with PTX, consequently increasing cell death. In addition, NBO leads to intracellular reactive oxygen species and induced endoplasmic reticulum (ER) stress through the CCAAT/enhancer-binding protein homologous protein (CHOP) signaling pathway. Conclusion: In summary, NBO increased cell death in lung cancer cells and promoted PTX re-sensitization in A549/PR cells through apoptosis and CHOP-mediated ER stress. [ABSTRACT FROM AUTHOR]

Abstract Background All of the existing medication and surgical therapies currently cannot completely inhibit intracerebral hemorrhage (ICH)-mediated brain damage, resulting in disability in different degrees in the involved patients. Normobaric oxygenation (NBO) was reported attenuating ischemic brain injury. Herein, we aimed to explore the safety and efficacy of NBO on rescuing the damaged brain tissues secondary to acute ICH, especially those in the perihematoma area being threatened by ischemia and hypoxia. Methods A total of 150 patients confirmed as acute spontaneous ICH by computed tomography (CT) within 6 h after symptoms onset, will enroll in this study after signing the informed consent, and enter into the NBO group or control group randomly according to a random number. In the NBO group, patients will inhale high-flow oxygen (8 L/min, 1 h each time for 6 cycles daily) and intake low-flow oxygen (2 L/min) in intermittent periods by mask for a total of 7 days. While in the control group, patients will breathe in only low-flow oxygen (2 L/min) by mask for 7 consecutive days. Computed tomography and perfusion (CT/CTP) will be used to evaluate cerebral perfusion status and brain edema. CT and CTP maps in the two groups at baseline and day 7 and 14 after NBO or low-flow oxygen control will be compared. The primary endpoint is mRS at both Day14 post-ICH and the end of the 3rd month follow-up. The secondary endpoints include NIHSS and plasma biomarkers at baseline and Day-1, 7, and 14 after treatment, as well as the NIHSS at the end of the 3rd month post-ICH and the incidence of bleeding recurrence and the mortalities within 3 months post-ICH. Discussion This study will provide preliminary clinical evidence about the safety and efficacy of NBO on correcting acute ICH and explore some mechanisms accordingly, to offer reference for larger clinical trials in the future. Trial registration ClinicalTrials.gov NCT04144868 . Retrospectively registered on October 29, 2019.

Intravenous thrombolysis elevates the prognostic level of acute ischemic stroke (AIS) patients. Normobaric hyperoxia (NBO) delays the progression of the infarct core and promotes neurological recovery. However, it is uncertain whether NBO can further raise the prognostic level of AIS patients based on intravenous thrombolysis. To explore the efficacy and safety of NBO combined with intravenous thrombolysis on AIS patients. This observational study included anterior circulation stroke patients who received intravenous thrombolysis within 4.5 h after stroke onset. These patients were divided into two groups based on whether or not they received NBO therapy. The baseline data and the prognosis of the two groups were compared. The primary outcome was the proportion of functional independence (modified Rankin Scale 0–2) at 90 days post discharge. A total of 227 patients were included in this study. 125 patients received NBO therapy combined with intravenous thrombolysis, while 102 patients received intravenous thrombolysis only. Overall, the rate of recanalization was 83.3%. Consequently, 101 patients (80.8%) who received NBO combined with intravenous thrombolysis and 63 patients (61.8%) in the control group achieved functional independence (P = 0.002). Multivariable logistic regression analysis showed that NBO combined with intravenous thrombolysis over intravenous thrombolysis alone was associated with 90-day functional independence (OR: 2.318; 95% CI: 1.226–4.381; P = 0.01). This study verified the efficacy and safety of NBO combined with intravenous thrombolysis in AIS patients. Prospective study is needed to further substantiate these findings. [ABSTRACT FROM AUTHOR]

The "Normobaric Oxygen Paradox" (NOP) is a physiologic mechanism that induces an increase of endogenous erythropoietin (EPO) production by creating a state of relative hypoxia in subjects previously exposed to hyperoxia, followed by a rapid return to normoxia. Oxygen exposure duration and inspired oxygen fraction required to observe a significant increase in EPO or hemoglobin are not clearly defined. Consequently, we here study the effect of one model of relative hypoxia on EPO, reticulocytes and hemoglobin stimulation in patients after surgery. Patients were prospectively randomized in two groups. The O2 group (n = 10) received 100% oxygen for 1 h per day for eight consecutive days, via a non-rebreathing mask. The control group (n = 12) received no oxygen variation. Serum EPO, hemoglobin and reticulocyte count were measured on admission and postoperatively on days seven and nine. Percentage EPO at day nine with respect to the baseline value was significantly elevated within the groups [O2 group: 323.7 (SD ± 139.0); control group: 365.6 (SD± 162.0)] but not between them. No significant difference was found between the groups in terms of reticulocytes count and hemoglobin. Our NOP model showed no difference on EPO increase between the two groups. However, both groups expressed separately significant EPO elevation. [ABSTRACT FROM AUTHOR]

The “Normobaric Oxygen Paradox” (NOP) is a physiologic mechanism that induces an increase of endogenous erythropoietin (EPO) production by creating a state of relative hypoxia in subjects previously exposed to hyperoxia, followed by a rapid return to normoxia. Oxygen exposure duration and inspired oxygen fraction required to observe a significant increase in EPO or hemoglobin are not clearly defined. Consequently, we here study the effect of one model of relative hypoxia on EPO, reticulocytes and hemoglobin stimulation in patients after surgery. Patients were prospectively randomized in two groups. The O2 group (n = 10) received 100% oxygen for 1 h per day for eight consecutive days, via a non-rebreathing mask. The control group (n = 12) received no oxygen variation. Serum EPO, hemoglobin and reticulocyte count were measured on admission and postoperatively on days seven and nine. Percentage EPO at day nine with respect to the baseline value was significantly elevated within the groups [O2 group: 323.7 (SD ± 139.0); control group: 365.6 (SD± 162.0)] but not between them. No significant difference was found between the groups in terms of reticulocytes count and hemoglobin. Our NOP model showed no difference on EPO increase between the two groups. However, both groups expressed separately significant EPO elevation.

Purpose: We investigated the effects of a relatively inexpensive, non-invasive, short-term treatment with low-dose normobaric hyperoxia (NBH) on macular edema in patients with retinal vein occlusion (RVO). Methods: Participants with macular edema associated with RVO were treated with 5 LPM of NBH via facemask (40% fraction of inspired oxygen, FIO2) for 3 h. Patients with non-fovea involving edema who elected to be observed returned for a second treatment 1 month later to test reproducibility. Results: A 3-h session of NBH (n = 45) resulted in decreased maximum macular thickness (MMT) (mean 7.10%, t34=9.63 P<.001) and central macular thickness (CMT) (mean 4.64%, t34=6.90, P<.001) when compared to untreated eyes with RVO measured over the same period of time (n = 12) or their healthy fellow eye (n = 34; MMT:t34=−9.60, P<.001;CMT: t34=−6.72, P<.001). Patients who had a second NBH treatment 1 month later experienced a recurrence of their edema, but demonstrated a similar significant reduction in MMT and CMT after the second NBH treatment. Conclusions: Three-hour treatment with 40% FIO2 NBH results in a significant reduction in MMT and CMT. This study supports an ischemic mechanism for macular edema associated with retinal vein occlusion. Translational relevance: Short-term low-dose normobaric hyperoxia is a simple, inexpensive, and ubiquitous treatment that may provide an alternate or adjunctive approach to treating macular edema in patients who are resistant to or cannot afford anti-VEGF medications. [ABSTRACT FROM AUTHOR]

Background: All of the existing medication and surgical therapies currently cannot completely inhibit intracerebral hemorrhage (ICH)-mediated brain damage, resulting in disability in different degrees in the involved patients. Normobaric oxygenation (NBO) was reported attenuating ischemic brain injury. Herein, we aimed to explore the safety and efficacy of NBO on rescuing the damaged brain tissues secondary to acute ICH, especially those in the perihematoma area being threatened by ischemia and hypoxia.Methods: A total of 150 patients confirmed as acute spontaneous ICH by computed tomography (CT) within 6 h after symptoms onset, will enroll in this study after signing the informed consent, and enter into the NBO group or control group randomly according to a random number. In the NBO group, patients will inhale high-flow oxygen (8 L/min, 1 h each time for 6 cycles daily) and intake low-flow oxygen (2 L/min) in intermittent periods by mask for a total of 7 days. While in the control group, patients will breathe in only low-flow oxygen (2 L/min) by mask for 7 consecutive days. Computed tomography and perfusion (CT/CTP) will be used to evaluate cerebral perfusion status and brain edema. CT and CTP maps in the two groups at baseline and day 7 and 14 after NBO or low-flow oxygen control will be compared. The primary endpoint is mRS at both Day14 post-ICH and the end of the 3rd month follow-up. The secondary endpoints include NIHSS and plasma biomarkers at baseline and Day-1, 7, and 14 after treatment, as well as the NIHSS at the end of the 3rd month post-ICH and the incidence of bleeding recurrence and the mortalities within 3 months post-ICH.Discussion: This study will provide preliminary clinical evidence about the safety and efficacy of NBO on correcting acute ICH and explore some mechanisms accordingly, to offer reference for larger clinical trials in the future.Trial Registration: ClinicalTrials.gov NCT04144868 . Retrospectively registered on October 29, 2019. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a significant clinical problem associated with poor outcome. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery, and intrarenal hypoxia is a hallmark of AKI and progression to chronic kidney disease. However, the role of intrarenal hypoxia per se in the recovery from an ischemic insult is presently unclear. The present study was designed to investigate 1) the role of systemic hypoxia in the acute progression and recovery of AKI and 2) whether increased intrarenal oxygenation improves recovery from an ischemic insult. Anesthetized male Sprague-Dawley rats were subjected to unilateral warm renal ischemia for 45 min followed by 2 h of reperfusion under systemic hypoxia (10% inspired oxygen), normoxia (21% inspired oxygen), or hyperoxia (60% inspired oxygen). Intrarenal oxygen tension was successfully manipulated by altering the inspired oxygen. Glomerular filtration rate (GFR) before the ischemic insult was independent of intrarenal oxygen tension. GFR during the recovery from the ischemic insult was significantly lower compared with baseline in all groups (3 ± 1%, 13 ± 1%, and 30 ± 11% of baseline for hypoxia, normoxia, and hyperoxia, respectively). However, GFR was significantly higher in hyperoxia than hypoxia (P < 0.05, hypoxia vs. hyperoxia). During recovery, renal blood flow was only reduced in hyperoxia, as a consequence of increased renal vascular resistance. In conclusion, the present study demonstrates that renal function during the recovery from an ischemic insult is dependent on intrarenal oxygen availability, and normobaric hyperoxia treatment has the potential to protect kidney function. [ABSTRACT FROM AUTHOR]

As we all know that stroke is still a leading cause of death and acquired disability. Etiological treatment and brain protection are equally important. This review aimed to summarize the advance of normobaric-hyperoxia (NBHO) on brain protection in the setting of experimental stroke and brain trauma. We analyzed the data from relevant studies published on PubMed Central (PMC) and EMBASE, about NBHO on brain protection in the setting of experimental ischemic and hemorrhagic strokes and brain trauma, which revealed that NBHO had important value on improving hypoxia and attenuating ischemia damage. The mechanisms of NBHO involved increasing the content of oxygen in brain tissues, restoring the function of mitochondria, enhancing the metabolism of neurons, alleviating blood-brain barrier (BBB) damage, weakening brain cell edema, reducing intracranial pressure, and improving cerebral blood flow, especially in the surrounding of injured area of the brain, to make the neurons in penumbral area alive. Compared to hyperbaric oxygen (HBO), NBHO is more safe and more easily to transform to clinical use, whereby, further studies about the safety and efficacy as well as the proper treatment protocol of NBHO on human may be still needed.

Blast-induced traumatic brain injury (bTBI) is a leading cause of disability and mortality in soldiers during the conflicts in Iraq and Afghanistan. Although substantial clinical and animal studies have investigated the pathophysiology and treatments of bTBI, few effective therapies have been found, especially for the early rescue in the battlefield. The aim of this study is to evaluate neuroprotective effects of early normobaric hyperoxia (NBO) on bTBI. We established a rat model of bTBI caused by explosion in the cabin. It exhibited typical changes of mild bTBI, like impaired neurological function, brain edema, minor intracranial hemorrhage and neuron necrosis. The rats were divided into 4 groups (n = 12): Sham, Vehicle, hyperbaric oxygen (HBO) and NBO. Neurological function of the rats was assessed by the Neurological Severity Scores (NSS) at 24 h and 72 h after explosion. Serum interleukin-6 (IL-6), neuron specific enolase (NSE) and tau protein were measured at 24 h and 72 h after explosion. Brain water content was measured and Aquaporin-4 (AQP4) immunostaining was performed. Neuronal apoptosis was analyzed by TUNEL staining. NBO demonstrated curative effects on protecting the neurological function. Serum levels of NSE and tau protein were reduced at 24 h and 72 h after explosion. But the levels of IL-6 were not reduced significantly at both time points. Cerebral edema was alleviated. Simultaneously, AQP4 immunostaining of the hippocampus showed remarkably decreased expression after treatment. The number of apoptotic cells in hippocampus was also decreased. Compared with HBO, NBO is simple and convenient, and can be administered in remote areas. It may be a promising therapy for early rescue of bTBI in the battlefield. [ABSTRACT FROM AUTHOR]

Following renal ischemia-reperfusion injury (RIRI), because of the decrease in oxygen supply to the kidney, a large amount of oxygen-free radicals is generated, and in severe cases, tissue cells will undergo apoptosis or even die. Normobaric hyperoxia (NBHO) is a very common clinical adjuvant treatment. It restores the oxygen supply after renal ischemia and combats oxidative stress in tissues, thus playing a protective role. In this study, our aim is to elucidate the protective mechanism of NBHO inhalation in a rat RIRI model. We performed a surgical excision of the left kidney of the rat and established a right kidney solitary kidney model. Later, the right renal pedicle of the rat was clamped using a non-invasive vascular clamp for 45 min. After the vascular clamp was released and reperfused for 24 h, the rat was placed in a closed oxygen chamber. It was subjected to inhalation of high-concentration oxygen (50%–55%), 2 h daily, for 7 days.RIRI induces postoperative weight loss, impaired renal function, increased oxygen free radicals, reduced antioxidant substances, increased histopathological damage, and increased levels of apoptosis. These effects were significantly improved after treatment with NBHO. At the same time, NBHO significantly increased the expression levels of Nrf2 and HO-1 in the tissues after RIRI. To verify whether HO-1 induced by Nrf2 is involved in the resistance to oxidative stress, after the rat RIRI and before inhaling NBHO, we intraperitoneally injected HO-1 specific inhibitor zinc protoporphyrin (ZnPP) (45 μmol/Kg). However, we found that ZnPP reversed the protective effect of NBHO on RIRI in rats. Combining all the results, we have demonstrated the protective effect of NBHO on RIRI, which can be at least partially attributed to the activation of the Nrf2/HO-1 antioxidative stress pathway. • The first direct evidence that normobaric hyperoxia has a protective effect after renal ischemia-reperfusion injury. • The first suggested that its role may be achieved by activating the Nrf2/HO-1 anti-oxidative stress pathway. • Further validated the role of Nrf2/HO-1 antioxidative stress pathway in renal ischemia-reperfusion injury. • Normobaric hyperoxia is a simple, low-cost, and less side effect clinical treatment method. • Provide new ideas for clinical adjuvant therapy after renal ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

As we all know that stroke is still a leading cause of death and acquired disability. Etiological treatment and brain protection are equally important. This review aimed to summarize the advance of normobaric-hyperoxia (NBHO) on brain protection in the setting of experimental stroke and brain trauma. We analyzed the data from relevant studies published on PubMed Central (PMC) and EMBASE, about NBHO on brain protection in the setting of experimental ischemic and hemorrhagic strokes and brain trauma, which revealed that NBHO had important value on improving hypoxia and attenuating ischemia damage. The mechanisms of NBHO involved increasing the content of oxygen in brain tissues, restoring the function of mitochondria, enhancing the metabolism of neurons, alleviating blood-brain barrier (BBB) damage, weakening brain cell edema, reducing intracranial pressure, and improving cerebral blood flow, especially in the surrounding of injured area of the brain, to make the neurons in penumbral area alive. Compared to hyperbaric oxygen (HBO), NBHO is more safe and more easily to transform to clinical use, whereby, further studies about the safety and efficacy as well as the proper treatment protocol of NBHO on human may be still needed. [ABSTRACT FROM AUTHOR]

Abstract Background: Recent studies indicate that hyperoxia has a significant therapeutic effect in the acute ischemic injury. The role of intracellular kinases, including ERK, has been posed in the phenomenon of ischemic tolerance. In the present study, the effect of intermittent normobaric hyperoxia on the activity of ERK in the stroke model was studied Material and Methods: This is an experimental study. Animals include 4 groups (sham, hyperoxia–sham, stroke and hyperoxia–stroke); each group consisted of 6 male Wistar rats in the weight range of 250 to 350 grams. Hyperoxia groups were exposed to 95% inspired oxygen for 4 h/day and 6 consecutive days. Oxygen concentration in the control groups was 21% (normoxia, room air). After 24h, the stroke group animals were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24h reperfusion, neurological deficit scores (NDS) and ERK activity were assessed. Results: 5 hours after MCAO, stroke groups showed a significant increase in ERK activity in the cortex (p

Objective(s):Every year, a large number of people lose their lives due to stroke. Stroke is the second leading cause of death worldwide. Surprisingly, recent studies have shown that preconditioning with hyperoxia (HO) increases tissue tolerance to ischemia, ultimately reducing damages caused by stroke. Addressed in this study are beneficial contributions from HO preconditioning into reduced harm to be incurred by the attack, as well as its effect on the expression levels of vascular endothelial growth factor (VEGF) and endostatin. Materials and Methods: A set of experiments was conducted where a number of rats were divided into three groups. The animals in the first group received 90% oxygen for 4 hr a day, for 6 days. The second group was housed in room air and the third group was a sham (surgical stress). After 60 min of ischemia, 24 hr blood flow, neurological deficit score (NDS) and infarct volume (IV) in the group MCAO (Middle Cerebral Artery Occlusion) were investigated. Immediately following a 48 hr HO pre-treatment, sampling was performed to measure the expression levels of VEGF and endostatin. Results: Preconditioning with alternating HO led to reduced infarct volume and NDS. Moreover, pre-treatment with HO resulted in increased VEGF expression while decreasing endostatin. Conclusion: Although further studies are deemed necessary to clarify the mechanisms of ischemic tolerance, apparently, somewhat intermittent hyperoxia can be associated with positive impacts by increasing VEGF and decreasing expression of endostatin.

Background: Ischemic stroke is one of the most severe cerebrovascular diseases that leads to disability and death and seriously endangers health and quality of life. Insufficient oxygen supply is a critical factor leading to ischemic brain injury. However, effective therapies for ischemic stroke are lacking. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve prognosis after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBHO) has been shown to have neuroprotective effects during ischemic stroke and is considered an appropriate neuroprotective therapy for ischemic stroke. Evidence indicates that NBHO plays a neuroprotective role through different mechanisms in acute ischemic stroke. Recent studies have also reported that combinations with other drug therapies can enhance the efficacy of NBHO in ischemic stroke. Here, we aimed to provide a summary of the potential mechanisms underlying the use of NBHO in ischemic stroke and an overview of the benefits of NBHO in ischemic stroke., Methods: We screened 83 articles on PubMed and other websites. A quick review was conducted, including clinical trials, animal trials, and reviews of studies in the field of NBHO treatment published before July 1, 2023. The results were described and synthesized, and the bias risk and evidence quality of all included studies were assessed., Results: The results were divided into four categories: the mechanism of NBHO, animal and clinical trials of NBHO, the clinical application and prospects of NBHO, and adverse reactions of NBHO., Conclusion: NBHO is a simple, non-invasive therapy that may be delivered early after stroke onset, with promising potential for the treatment of acute ischemic stroke. However, the optimal therapeutic regimen remains uncertain. Further studies are needed to confirm its efficacy and safety., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Abstract—A hypothesis about the mechanism of radiosensitizing effect of hyperoxia during irradiation on the course and outcome of gastrointestinal radiation syndrome in the absence of significant modification of the course of hematopoietic radiation syndrome is presented. The important role of an increased production of reactive oxygen species (ROS) in hyperoxia in promoting gastrointestinal radiation injury in the absence of a significant contribution of the "oxygen effect" to this process is considered. The role of the accumulation of the toxic effects of ROS under repeated hyperoxia with exposure to fractionated irradiation in exacerbating acute radiation syndrome is emphasized. Attention is paid to the role of the preliminary daily stress effect of vibration on the potentiation of the radiosensitizing effect of hyperoxia on the course of gastrointestinal radiation syndrome. The metabolic changes in the regulation of the energy supply of the body under combined exposure to ionizing radiation and hyperoxia are analyzed. Possible mechanisms of radiomitigating effect of hyperoxia on the hematopoietic tissue, manifested during short-term 100% oxygen breathing before or immediately after irradiation of animals are considered. The signaling role of ROS and the cytostatic effect caused by hyperoxia in enhancing the postradiation recovery of hemopoietic tissue is emphasized. [ABSTRACT FROM AUTHOR]

Purpose of the article: To determine whether intraoperative ventilation with pure oxygen during the last stage of surgery reduces the occurrence and volume of postoperative pneumocephalus when compared to conventional air/oxygen mixture in patients undergoing craniotomy. Material and Methods: prospective randomized single-blinded study to compare the rate of occurrence and volume of postoperative pneumocephalus in patients undergoing craniotomy receiving intraoperative ventilation with pure oxygen (Group B) versus a conventional air/oxygen 1:1 mixture (Group A) during the last stage of surgery. This trial was registered in ClinicalTrials.gov #NCT02722928, protocol number 2015H0032. Results: One hundred patients were randomized into group 'A' and group 'B'. Seventy patients were included in the final analysis with 39 patients allocated in group 'A' and 31 patients in group 'B'. Median and IQR were used for postoperative penumocephalus volume. Group A: 9.65 [3.61–23.20]; Group B: 7.06 [2.70–20.1]. Our study showed no prophylactic effect on postoperative pneumocephalus volume when using mechanical ventilation with higher oxygen concentrations than the standard FiO2 during the last stage of surgery in patients undergoing craniotomy (p =.47). No statistical difference was found in SICU LOS between groups (median 1,380 min [group A] versus 1,524 min [group B]; p =.18). Conclusion: The use of intraoperative mechanical ventilation with pure oxygen was not associated with a prophylactic effect on the occurrence and extent of postoperative pneumocephalus in our patient setting. Published literature describing the extent of postoperative pneumocephalus is limited or highly variable among institutions. [ABSTRACT FROM AUTHOR]

Exposure to normobaric hyperoxia (NH) is known to increase the production of reactive oxygen species (ROS) by mitochondria. The present study was designed to examine mitochondrial ultrastructure morphological changes in the cortical brainin relation to glutathione peroxidase (GPX) activity and free radicals (FR) productions in brain tissue during hyperoxia exposure. The experimental groups were exposed to NH for 24 and 48 h continuously. Following the exposure periods, animals were sacrificed and cortical tissues were divided randomly into two parts; the first part was processed for the ultrastructural examination and the second was homogenized for GPX and FR determinations. Analysis of variance (ANOVA) showed that the main effects of O2 exposure periods were significant (p<0.05) for GPX and FR. Pair-wise means comparisons showed that NH elevated the average (+SE) GPX activity significantly (p<0.05) from the baseline control value of 5670.99+556.34 to13748.42+283.04 and 15134.19+1529.26 U/L with increasing length of NH exposure period from 24 to 48 h, respectively. Similarly, FR production was increased significantly (p<0.05) to 169.73+10.31 and 185.33+21.87, above baseline control of 105.27+5.25 Unit. Ultrastructure examination showed that O2 breathing for 48 h resulted in giant and swelled mitochondria associated with diluted inner membrane and damaged cristae. These mitochondria pathological alterations were associated with damages of myelin, axonal and cellular organelles. Normobaric-hyperoxia inducts mitochondria oxidative stress (MOS) and the subsequent rise of ROS causes variety of ultrastructure morphological pathological alterations in the organelles of cortical brain cells. [ABSTRACT FROM AUTHOR]

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There has been no major advancement in a quarter of a century for the treatment of acute severe traumatic brain injury (TBI). This review summarizes 40 years of clinical and pre-clinical research on the treatment of acute TBI with hyperbaric oxygen therapy (HBO2) in the context of an impending National Institute of Neurologic Disorders and Stroke-funded, multi-center, randomized, adaptive Phase II clinical trial -the Hyperbaric Oxygen Brain Injury Treatment (HOBIT) trial. Thirty studies (eight clinical and 22 pre-clinical) that administered HBO2 within 30 days of a TBI were identified from PubMed searches. The pre-clinical studies consistently reported positive treatment effects across a variety of outcome measures with almost no safety concerns, thus providing strong proof-of-concept evidence for treating severe TBI in the acute setting. Of the eight clinical studies reviewed, four were based on the senior author's (GR) investigation of HBO2 as a treatment for acute severe TBI. These studies provided evidence that HBO2 significantly improves physiologic measures without causing cerebral or pulmonary toxicity and can potentially improve clinical outcome. These results were consistent across the other four reviewed clinical studies, thus providing preliminary clinical data supporting the HOBIT trial. This comprehensive review demonstrates that HBO2 has the potential to be the first significant treatment in the acute phase of severe TBI. [ABSTRACT FROM AUTHOR]

Objective(s):Gentamicin sulphate (GS) nephrotoxicity seems to be related to the generation of reactive oxygen species. There is evidence that oxygen preconditioning increases the activity of antioxidant enzymes. Materials and Methods: Forty eight female rats were divided into 6 groups (n=8) as follows: group 1 was the control, group 2 received daily GS, groups 3,4 and 5 received oxygen 2 hr/day for 2 days, 4 hr/day for 2 days, 4 hr/day for 4 days, recpectively and then received daily GS, group 6 received oxygen 2 hr/day for 2 days and then received 2 hr oxygen before daily GS injection. Oxygen (with 90% purity) used at the flow rate of 4 l/min. GS administred for 8 days (100 mg/kg, IP). Tissue sections prepared from the left kidney, stained with PAS method and then studied hisopathologically and stereologically. The right kidneys were homogenized and the supernatants were prepared. Serum MDA, creatinine and urea, renal MDA, gluthatione and catalase activity were measured. The data were analyzed by Mann-Whitney U test at the significant level of PResults: Oxygen therapy significantly improves serum creatinine and urea, preserve tubular volume density, reduce tubular necrosis in groups 4 and 6 compared to group 2. Oxygen therapy significantly increases renal catalase in groups 4 and 6 compared to group 2. Conclusion: Pretreatment with normobaric hyperoxia and daily oxygen therapy improved gentamicin nephrotoxicity possibly via inhibition of lipid peroxidation and increasing the renal catalase activity but could not restore any parameter at the same levels as control group.

Background: Recent studies indicate that hyperoxia has a significant therapeutic effect in the acute ischemic injury. The role of intracellular kinases, including ERK, has been posed in the phenomenon of ischemic tolerance. In the present study, the effect of intermittent normobaric hyperoxia on the activity of ERK in the stroke model was studied Material and Methods: This is an experimental study. Animals include 4 groups (sham, hyperoxia–sham, stroke and hyperoxia–stroke); each group consisted of 6 male Wistar rats in the weight range of 250 to 350 grams. Hyperoxia groups were exposed to 95% inspired oxygen for 4 h/day and 6 consecutive days. Oxygen concentration in the control groups was 21% (normoxia, room air). After 24h, the stroke group animals were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24h reperfusion, neurological deficit scores (NDS) and ERK activity were assessed. Results: 5 hours after MCAO, stroke groups showed a significant increase in ERK activity in the cortex (p <0.01) and subcortex (p <0.001). At the same time, hyperoxia significantly increased the activity of ERK in cortex compared to the normoxia group (p<0.05). In subcortex, hyperoxia had no significant effect on ERK activity. Twenty-four hours after MCAO, stroke groups showed a significant reduction in ERK activity in the cortex (p <0.001) and subcortex (p <0.05). 24hr after MCAO, The activity of ERK in the hyperoxia groups; in both cortex and subcortex areas was significantly higher than that of the normoxia groups (p<0.05). Also, hyperoxia caused a significant decrease in NDS (p=0.0220). Conclusion: Increased levels of ERK activity in the hyperoxia groups can be used to protect the nervous system, but the presence of other malicious factors may have been more effective in some cases, so that hyperoxia alone hasn't been able to prevent stroke progression. [ABSTRACT FROM AUTHOR]

Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia.Clarifying the underlying pathophysiology of HIBI is imperative and has been the focus of considerable research to identify therapeutic targets. Most notably, targeted temperature management has been studied rigorously in preventing secondary injury after HIBI and is associated with improved outcome compared with hyperthermia. Recent advances point to important roles of anemia, carbon dioxide perturbations, hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury after HIBI and adverse outcomes. Furthermore, breakthroughs in the individualization of perfusion targets for patients with HIBI using cerebral autoregulation monitoring represent an attractive area of future work with therapeutic implications.We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized. [ABSTRACT FROM AUTHOR]

Background: The normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of 'relative hypoxia' which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients. Methods: In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) ≤0.5 and PaO2/FiO2 ≥ 200 mmHg underwent a 2-hour exposure to hyperoxia (FiO2 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24 h and 48 h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2 h of hyperoxia (t1) and 2 h after returning to their baseline FiO2 (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test. Results: EPO increased within 48 h in patients exposed to hyperoxia from 16.1 [7.4-20.2] to 22.9 [14.1-37.2] IU/L (p = 0.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79-90] of baseline). The response after 2 h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO2. Conclusions: A two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48 h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis. Trial registration: ClinicalTrials.gov (www.clinicaltrials.gov), NCT02481843, registered 15th June 2015, retrospectively registered [ABSTRACT FROM AUTHOR]

Objective(s): Every year, a large number of people lose their lives due to stroke. Stroke is the second leading cause of death worldwide. Surprisingly, recent studies have shown that preconditioning with hyperoxia (HO) increases tissue tolerance to ischemia, ultimately reducing damages caused by stroke. Addressed in this study are beneficial contributions from HO preconditioning into reduced harm to be incurred by the attack, as well as its effect on the expression levels of vascular endothelial growth factor (VEGF) and endostatin. Materials and Methods: A set of experiments was conducted where a number of rats were divided into three groups. The animals in the first group received 90% oxygen for 4 hr a day, for 6 days. The second group was housed in room air and the third group was a sham (surgical stress). After 60 min of ischemia, 24 hr blood flow, neurological deficit score (NDS) and infarct volume (IV) in the group MCAO (Middle Cerebral Artery Occlusion) were investigated. Immediately following a 48 hr HO pretreatment, sampling was performed to measure the expression levels of VEGF and endostatin. Results: Preconditioning with alternating HO led to reduced infarct volume and NDS. Moreover, pretreatment with HO resulted in increased VEGF expression while decreasing endostatin. Conclusion: Although further studies are deemed necessary to clarify the mechanisms of ischemic tolerance, apparently, somewhat intermittent hyperoxia can be associated with positive impacts by increasing VEGF and decreasing expression of endostatin. [ABSTRACT FROM AUTHOR]

The presence of a salvageable penumbra, a region of ischemic brain tissue with sufficient energy for short-term survival, has been widely agreed as the premise for thrombolytic therapy with tissue plasminogen activator (tPA), which remains the only United States Food and Drug Administration (FDA) approved treatment for acute ischemia stroke. However, the use of tPA has been profoundly constrained due to its narrow therapeutic time window and the increased risk of potentially deadly hemorrhagic transformation (HT). Blood brain barrier (BBB) damage within the thrombolytic time window is an indicator for tPA-induced HT and both normobaric hyperoxia (NBO) and hypothermia have been shown to protect the BBB from ischemia/reperfusion injury. Therefore, providing the O2 as soon as possible (NBO treatment), freezing the brain (hypothermia treatment) to slow down ischemia-induced BBB damage or their combined use may extend the time window for the treatment of tPA. In this review, we summarize the protective effects of NBO, hypothermia or their use combined with tPA on ischemia stroke, based on which, the combination of NBO and hypothermia may be an ideal early stroke treatment to preserve the ischemic penumbra. Given this, there is an urge for large randomized controlled trials to address the effect. [ABSTRACT FROM AUTHOR]

Introduction: Hyperoxia is an easy access preconditioner which attracts the researcher to use it in the clinic. Drug dependence is a widespread prevalence among different societies and one of the confounding factors in many diseases. Among different drugs, morphine dependence has shown preconditioning effects. According to both widespread phenomenon of drug addiction and use of hyperoxia in the clinic, there is a high probability of interaction between these two preconditioner factors on the ischemia-reperfusion injuries. Therefore, in this study, interaction of these two preconditioners on the ischemia-reperfusion injuries has been investigated. Method: Each containing ten rats, hearts were isolated in langendorff setup and after local ischemia, release of creatine phosphokinase (as a tissue damage index) and rate pressure product (as a mechanical function index) were measured. Furthermore, episode numbers of ventricular tachycardia and ventricular fibrillation (as arrhythmias indices) during ischemia and reperfusion period were studied separately. Results: normobaric hyperoxia in isolated morphine dependent rat hearts decreased creatine phosphokinase and increased mechanical function during reperfusion period. However, there was no significant difference in arrhythmias toward each of these preconditioners alone. Conclusion: preconditioning with normobaric hyperoxia in isolated morphine dependent rat heart induced reduction of tissue damage and improved cardiac function.

Objective: Ischemic preconditioning (IPC) is an endogenous phenomenon that caninduce ischemic tolerance (IT) in variety of organs such as brain. In this study, weexamined the intermittent and prolonged dose of normobaric hyperoxia (NBHO)in neurologic deficit scores, NF-kB activity, and TNF-α converting enzyme (TACE)expression.Materials and Methods: The rats were divided to four main groups. First twogroups were exposed to HO divided in prolonged (24hrs; PrHO) and intermittent(4h×6 days; InHO) groups. Second two groups acted as control groups and theywere exposed to 21% oxygen with the following condition: in the same chamber(room air, RA), continuously (24hrs; Pr RA) and discontinuously (4h×6days; InRA).Each group was subdivided to three subgroups. After 24hrs, first subgroup wassubjected to 60mins MCAO followed by 24hrs of reperfusion. Then, IT, induced byInHO and PrHO, was measured by neurologic deficit scores and infarct volume.Second and third subgroups were respectively called sham-operated subgroup andintact subgroup designed to assess the effect of HO on NF-kB activity and TNF-αconverting enzyme expression.Results: Our findings indicate that InHO and PrHO are involved in the induction ofIT. Pretreatment with InHO and PrHO reduce neurologic deficit scores and infarctvolume significantly. InHO and PrHO increase NF-kB activity and TNF-α convertingenzyme expression with different degrees. Also, InHO with ischemia increase NF-kBactivity and TNF-α converting enzyme expression significantly.Conclusion: Although further studies are needed to clarify the mechanisms ofischemic tolerance, InHO and PrHO seem partly to exert their effects via increasingNF-kB activity and up regulation of TNF-α converting enzyme.

Acute ischemic stroke is a common and serious neurological disease. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve outcomes after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBO), an easily applicable and non-invasive method, shows protective effects on acute ischemic stroke animals and patients in pilot studies. However, many critical scientific questions are still unclear, such as the therapeutic time window of NBO, the long-term effects and the benefits of NBO in large clinic trials. In this article, we review the current literatures on NBO treatment of acute ischemic stroke in preclinical and clinical studies and try to analyze and identify the key gaps or unknowns in our understanding about NBO. Based on these analyses, we provide suggestions for future studies. [ABSTRACT FROM AUTHOR]