Received Hyperbaric Oxygen Treatment Research Articles

Enhancement of cognitive function in mice with Alzheimer's disease through hyperbaric oxygen-induced activation of cellular autophagy.

In this study, we examined the effectiveness of hyperbaric oxygen (HBO) therapy in ameliorating cognitive deficits in mice with Alzheimer's disease (AD), while also assessing its impact on the autophagic pathway within the context of AD. 20 double-transgenic mice expressing the amyloid precursor protein and presenilin 1 (APP/PS1) were purposefully selected and randomly assigned to groups A and B. Concurrently, 20 C57BL/6 mice were chosen and randomly categorized into groups C and D, each consisting of 10 mice. Mice in groups B and D received HBO treatment. The Morris water maze assay was used to assess changes in mouse behavior. Immunohistochemistry techniques were used to quantify the expression levels of amyloid-beta 42 (Aβ42) and microtubule-associated protein 1A/1B-light chain 3 (LC3) in hippocampal tissues, while western blot analysis was used to investigate the levels of LC3-II, p62, phosphoinositide 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) proteins within hippocampal tissues. Mice allocated to group B exhibited reduced escape latency and prolonged dwell time in the target quadrant compared to other groups. Histological examination revealed conspicuous plaque-like deposits of Aβ42 in the hippocampal tissues of mice in groups A and B. Group B displayed diminished Aβ42-positive reactants and augmented microtubule-associated protein 1A/1B-LC3-positive reactants compared to group A. LC3-positive reactants were also detected in the hippocampal tissues of mice in groups C and D, surpassing the levels observed in groups A and B. Furthermore, group B demonstrated significantly lower expression of mTOR protein and markedly higher expression of LC3-II protein in mouse hippocampal tissues when compared to group A (P < 0.05). Conversely, there were no significant disparities noted in PI3K and p62 protein expression between groups B and A. Notably, no discernible discrepancies were observed in the expression levels of mTOR, PI3K, LC3-II, and p62 proteins between groups C and D within mouse hippocampal tissues. HBO treatment demonstrates efficacy in enhancing cognitive function in mice with AD and holds promise as a potential therapeutic intervention for AD by facilitating the activation of the mTOR pathway-mediated autophagy.

Hyperbaric Oxygen Therapy Ameliorates Sperm Parameters in Apolipoprotein E Knockout Mice Testes by Attenuating Oxidative Stress and Inflammation.

Apolipoprotein E (ApoE) is a member of apolipoprotein (apo) family and plays critical role in lipid metabolism. In this study, the relationship between abnormal lipid metabolism caused by ApoE-deficient and male reproduction was investigated. The effect of hyperbaric oxygen (HBO) therapy on 7-month-old ApoE-knockout male mice was assessed subsequently. Mice were randomly divided into 3 groups: control group (WT), ApoE (- / -) group (AP-CON), and ApoE (- / -) plus HBO group (AP-HBO), which received HBO treatment. We found that ApoE knockout caused a decrease in male reproductive capacity due to the reduced total sperm motility, progressive motility (PR), and lower blastocyst formation rate. HBO treatment could accelerate serum lipoprotein metabolism including LDL, T-CHO, and TG and semen quality. As a result, fertilization and blastocyst formation of AP-HBO group were higher than that of AP-CON, proving positive therapeutic effect. Mechanism exploration found that HBO treatment ameliorated the testicular microenvironment by attenuating inflammatory factor production and oxidative stress, eventually improved the sperm motility. Collectively, our study provided more evidences of HBO treatment for improving the semen quality of patients with abnormal lipid metabolism caused by ApoE-deficient.

Idiopathic Sudden Sensorineural Hearing Loss: Is Hyperbaric Oxygen Treatment the Sooner and Longer, the Better?

(1) Background: We aimed to evaluate hearing benefits from hyperbaric oxygen (HBO) therapy in patients with Idiopathic Sudden Sensorineural Hearing Loss (ISSHL). (2) Methods: We performed a retrospective analysis of chart reviews on patients with ISSHL between Jan 2016 and Dec 2021. All patients were referred to receive HBO therapy by the department of Ear, Nose and Throat (ENT). Hearing gain was assessed based on pure-tone audiometry (PTA). Data were analyzed for 102 patients after 1 to 5 therapy sessions, and for 46 patients after 6 to 10 therapy sessions. (3) Results: After 1–5 HBO sessions, patients (N = 102) showed an improvement in 45 (44.1%) of the patients (p < 0.000). Also, improvements were found with patients showing different grades of ISSHL: 11 (26.8%) with slight-moderate, 11 (40.7%) with severe, and 23 (67.6%) with profound ISSHL. Significant treatment effects were found at different affected frequencies, especially the low frequency range. After 6–10 HBO sessions, patients (N = 46) showed similar treatment effects as after 1–5 HBO sessions, but no additional improvement. Moreover, patients who received HBO treatment within 12 days showed improvement effects 6.484 times greater (p < 0.000) compared with those who received treatment after 13 days. (4) Conclusions: The improvement of HBO therapy on ISSHL was significant after 1–5 sessions, with larger improvements for those suffering more serious symptoms. Further adding more HBO treatment sessions to 6–10, no further improvement was found. Patients starting HBO therapy within 12 days of ISSHL showed 6.484 times greater improvements compared with those starting HBO therapy later.

The mechanism by which hyperbaric oxygen treatment alleviates spinal cord injury: genome-wide transcriptome analysis.

Accumulating studies have demonstrated that hyperbaric oxygen (HBO) treatment alleviates spinal cord injury (SCI). However, the underlying mechanism by which HBO alleviates SCI remains to be elucidated. In this study, we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI. We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice. We found 76 differentially co-expressed genes in sham-operated mice, SCI mice, and HBO-treated SCI mice. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component, biological process, and molecular function. We also found enriched functional pathways including ferroptosis, calcium signaling pathway, serotonergic synapse, hypoxia-inducible factor-1 signaling pathway, cholinergic synapse, and neuroactive ligand-receptor interaction. We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1 (heat shock protein beta 1), Hmox1 (heme oxygenase 1), Ftl1 (ferritin light polypeptide 1), Tnc (tenascin C) and Igfbp3 (insulin-like growth factor binding protein 3) and increased the expression of Slc5a7 (solute carrier family 5 choline transporter member 7) after SCI. These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment. Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention.

Effect of Nrf2 signaling pathway on the improvement of intestinal epithelial barrier dysfunction by hyperbaric oxygen treatment after spinal cord injury.

Disruption of the intestinal epithelial barrier following spinal cord injury (SCI) seriously affect long-term quality of life. Oxidative stress-induced epithelial cells' injury contributes to the epithelial barrier dysfunction. Hyperbaric oxygen (HBO) treatment has been proved to alleviate SCI. However, it is unclear whether or not HBO treatment affects intestinal barrier function following SCI. In this study, our purpose was to explore the impact of HBO treatment on intestinal epithelial barrier function and underlying mechanisms following SCI. An SCI model was established in rats, and the rats received HBO treatment. Intestinal injury, mucosal permeability, intercellular junction proteins, and oxidative stress indicators were evaluated in our study. We found that HBO treatment significantly alleviated intestinal histological damage, reduced mucosal permeability, and markedly prevented bacterial translocation. Furthermore, HBO treatment significantly increased the expression of Claudin-1 and E-cadherin, inhibited intestinal tissue oxidative stress as demonstrated by upregulation of superoxide dismutase and glutathione, and HBO downregulated malondialdehyde. Mechanically, we demonstrated that HBO treatment ameliorated intestinal oxidative stress possibly through upregulating nuclear factor E2-related factor 2 (Nrf2) and its downstream targets, Heme oxygenase-1(HO-1), NADH-quinone oxidoreductase-1(NQO-1), and glutamate cysteine ligase catalytic subunit (GCLC). These results suggested that HBO treatment triggered antioxidative effects against intestinal epithelial barrier dysfunction by promoting Nrf2 signaling pathway after SCI.

Hyperbaric oxygen therapy in carbon monoxide poisoning in pregnancy: Maternal and fetal outcome.

Closer monitoring and treatment is vital for pregnant carbon monoxide (CO) poisoning cases due to fetal poisoning component. Permanent damage can occur in both the mother and the baby. It may cause stillbirth even though no serious clinical symptoms occur in the mother. Hyperbaric oxygen (HBO) treatment is advised for all pregnant patients regardless of their clinical symptoms. Pregnant CO poisoning patients that received HBO treatment and their fetal status were evaluated in this study. Pregnant patients poisoned with CO treated in the same hyperbaric clinic were evaluated. Pregnant patients that received HBO treatment in a multiplace chamber were evaluated in terms of clinical status, demographic structure, laboratory tests, fetal effects and progress of the fetus until birth and 6months postpartum. A total number of 32 pregnant cases were treated. COHb values were over 20% (min 6.9- max 40.2) in 23 patients, 11 patients had a history of syncope. All patients took HBO treatment under 2.4 ATA pressure for 120min. 3 patients received more than 1 session of HBO treatments due to fetal stress; all other cases took 1 session of HBO treatment. No spontaneous abortus occurred in early follow-ups; only 4 babies were born prematurely. 2 of the babies were lost in the early phases after birth, due to causes non-related to CO poisoning complications (cyanotic heart disease, necrotising enterocolitis). No significant difference were observed in the comparison of laboratory results of patients with syncope and of those who did not have syncope and comparison of patients with COHb value higher than 20% and patients with COHb value lower than 20% (p>0.05). HBO is not advisable for pregnant patients except for CO poisoning. In this study it is observed that HBO treatment under 2.4 ATA pressure for 120min has no harmful effects on the mother and the fetus. It is observed that continuation of HBO treatment in the cases with fetal distress findings has beneficial effects. COHb levels and syncope were shown to have no significant effect on clinical symptoms and on blood tests.

Is Hyperbaric Oxygen Therapy Effective in Cisplatin-Induced Ototoxicity in Rats?

ObjectivesCisplatin is an antineoplastic agent, used in the treatment of different types of malignant neoplasms. Side effects such as ototoxicity, nephrotoxicity, and bone marrow toxicity are the main limitations of its clinical use. The aim of the present study was to evaluate the possible effects of hyperbaric oxygen (HBO) therapy as a protective agent in cisplatin-induced ototoxicity in rats.MethodsA total of 30 adult Wistar rats (60 ears) were divided into five equal groups. Group 1 is a control group; group 2 is HBO therapy group; group 3 received 15 mg/kg cisplatin intraperitoneally; group 4 received 15 mg/kg cisplatin intraperitoneally and HBO treatment on the same day; group 5 received 15 mg/kg cisplatin intraperitoneally and HBO treatment 72 hours later. The effect of ototoxicity was measured with distortion product otoacoustic emission testing performed on the days 1, 3, and 7.ResultsGroups 4 and 5 that received HBO treatment after cisplatin had better signal-to-noise ratio (SNR) values compared with group 3 that received only cisplatin (P<0.05). Compared with group 5, group 4 (same day HBO treatment) had better SNR values (P<0.05).ConclusionHBO was found effective for prevention of cisplatin-induced ototoxicity in rats. Our study differs from other studies regarding using a promising treatment, which does not expose subjects to extra stress.

Effect of combined chondroitinase ABC and hyperbaric oxygen therapy in a rat model of spinal cord injury.

The present study aimed to investigate the effect of combined hyperbaric oxygen (HBO) and chondroitinase ABC (ChABC) enzyme therapy in a rat model of spinal cord injury (SCI) and to explore the underlying mechanisms. A total of 48 healthy male Wistar rats were randomly divided into six groups: Sham, SCI, vehicle, HBO, ChABC enzyme and HBO + ChABC. Excluding the sham group, SCI was established in rats by a clip compression injury and rats subsequently received HBO treatment for 2 weeks with or without an intraspinal injection of 0.1 U/µl ChABC. Neuromotor functions were examined using the Basso-Beattie-Bresnahan locomotor rating scale and the inclined plane assessment at baseline and for 4 weeks following SCI establishment. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were also measured, in addition to the expression of glycogen synthase kinase-3β (GSK3β) and aquaporin 4 (AQP4). Results revealed that combined HBO and ChABC treatment significantly improved neuromotor function compared with the HBO or ChABC treatments alone. HBO and/or ChABC treatment significantly increased SOD and decreased MDA levels, as well as GSK3β expression, compared with the sham and SCI rats. The combined HBO and ChABC treatment significantly inhibited SCI-induced AQP4 expression, but ChABC alone did not. Functional recovery in the HBO + ChABC group was significantly increased compared with the HBO or ChABC groups. These results indicate that combined HBO and ChABC treatment is more effective in treating SCI than either therapy alone.

Neuroprotection of hyperbaric oxygen treatment for traumatic brain injury involving autophagy pathway in rats

Neuroprotection of hyperbaric oxygen treatment for traumatic brain injury involving autophagy pathway in rats Wen-Chao Liu, Liang Wen, Hao Wang, Jiang-Biao Gong, Tian-Xiang Zhan, Yuan-Yuan Meng, Xiao-Feng Yang Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People&rsquo;s Republic of China Abstract: In the present study, we evaluated the changes in autophagy after hyperbaric oxygen (HBO) treatment for traumatic brain injury (TBI) and investigated whether autophagy takes part in the neuroprotection after HBO treatment. Male Sprague Dawley rats were assigned to four groups randomly: sham injury, sham injury and HBO, TBI, and TBI and HBO. The HBO rats received HBO treatment for 100 min immediately after injury. Rats were sacrificed at 24 h after the brain injury and the levels of cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells in the injured cortex were measured to determine cell death. The expression levels of autophagy-associated proteins were measured by immunohistochemistry and Western blotting to assess changes in autophagy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell density and cleaved caspase-3 expression were increased 24 h after TBI. These increases were suppressed by post-TBI HBO treatment. Immunohistochemistry and Western blotting of autophagy-associated proteins showed that TBI can induce autophagy and that HBO treatment can further upregulate the expression of autophagy makers, as shown by an increase in LC3, ATG-5, and Beclin-1 expression and reduction in P62 expression. In conclusion, HBO treatment can reduce apoptosis and further upregulate autophagy in the injured cortex after brain injury, and the autophagy pathway may take part in the neuroprotection provided by HBO treatment for TBI. Keywords: autophagy, hyperbaric oxygen treatment, traumatic brain injury, apoptosis, neuroprotective effect

Effects of hyperbaric oxygen treatment on glucocorticoid receptor expression in the hipopocampus and on the behavior of rats under chronic restraint stress

Objective To explore the effects of hyperbaric oxygen treatment on chronic stress and glucocorticoid receptor (GR) expression in the hippocampus. Methods A total of 60 male Wistar rats were randomly divided into a restraint group, an HBO (hyperbaric oxygen) group, an HBO-restraint group and a control group using a random number table, each group with 15 animals. All the rats in the restraint and HBO groups were constrained by immobilizing their fore- and hind-limbs on a self-made frame for 3h daily for 21 days, and those in the HBO group received HBO treatment once daily for the same 21 days. The HBO-restraint group was immobilized in the morning and treated with HBO in the afternoon. The control group was reared without any special intervention. On the 1st, 11th and 21st day of treatment, rats from the different groups were assessed using the open field test. On the 21st day, all the animals were sacrificed and their brains were harvested to detect GR expression. Results In the open field test on the 11th day, the restraint group scored (131.0±20.6) in terms of motor level and (26.5±4.6) for exploratory behavior, both significantly higher than before restraint and significantly higher than those in the HBO-restraint group at the same time point. Immunofluorescence assay showed that GR expression in the hippocampus of the restraint group was significantly decreased compared with the control group. There was no significant difference, however, between the HBO-restraint group and the control group. Conclusion Chronic restraint stress induces changes in behavior and GR expression in rats which can be alleviated by hypbaric oxygen treatment. Key words: Chronic stress; Hyperbaric oxygenation; Chronic restraint; Open-field test; Receptors, glucocorticoid

Pilot Clinical Study Incorporating Hyperbaric Oxygen into Umbilical Cord Blood Transplantation

▪Background: Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells and may be the only allogeneic transplant option for some patients with hematologic malignancies. However, UCB transplantation is associated with delayed blood count recovery and engraftment. In preclinical studies, we have demonstrated that hyperbaric oxygen (HBO) therapy, given prior to cytokine expanded and gene-transduced UCB CD34+ cell infusion, improves peripheral blood, bone marrow, and spleen engraftment in a murine model. Based on these results, we started a pilot clinical trial primarily investigating the safety of HBO in the setting of UCB transplantation. Secondarily, we are evaluating the time to neutrophil and platelet count recovery and engraftment.As a potential marker for effective HBO therapy, we also evaluated serum erythropoietin (EPO) levels in transplanted patients prior to HBO therapy and again at time of transplantation.Materials/methods: Patients with hematological malignancies that require UCB transplantation, either reduced intensity or myeloablative, were included. On day 0, patients received HBO treatment consisting of exposure to 2.5 atmosphere absolutes for a total of 2 hours, in a single hyperbaric chamber, breathing 100% oxygen. Six hours from the start of HBO, single or double UCB units were infused and patients were followed daily for toxicity and blood count recovery. Serum EPO levels were measured by enzyme-linked immunosorbent assay (ELISA).Results: 18 patients were screened for this study, 9 were enrolled, and 9 were treated. The treated subjects were 5 males (56%) and 4 females (44%) with median age of 44 (23-70) who had acute myeloid leukemia (n=6), non-Hodgkin’s lymphoma (n=1), and acute lymphoblastic leukemia (n=2); all patients were in first (n=8) or second (n=1) complete remission. All but two patients received one UCB unit with a median total nucleated cell dose of 3.3 (2.7-4.5) ×107 /Kg recipient body weight and 6 of 9 patients received reduced intensity conditioning. All treated patients completed the planned therapy without a treatment limiting toxicity defined as the occurrence of any of the following complications within 24 hours of HBO: seizure disorder, pneumothorax, death or irreversible grade III or any grade IV toxicity that is determined by the treating physician to be, at least, likely related to HBO therapy. None of the patients experienced an unexpected toxicity. All patients engrafted except for one patient who demonstrated prompt autologous blood count recovery. Platelet count recovery was not assessable in one patient. Time to neutrophil count recovery (defined as the first of 3 consecutive days of an absolute neutrophil count (ANC) of greater than 500/μL) and time to platelet count recovery (defined as the first day of a sustained platelet count greater than 20 K/UL) were 16 (6-25) and 32 (8-87), respectively. 90% or higher donor chimerism was documented in peripheral blood/bone marrow of engrafted patients receiving reduced intensity regimen at a median of 18 (15-31) days post-transplant. Six of the 9 (67%) patients developed acute graft versus host disease at time of engraftment; 50% developed grade I, 33% had grade II and 17% had grade III. In 7 patients who had serum EPO levels assessed, median EPO levels at time of UCB infusion were lower than their median levels prior to HBO therapy (11.3 vs. 25.2 mU/mL).Conclusions: HBO therapy prior to UCB cell infusion appears to be well-tolerated in the setting of clinical umbilical cord blood transplantation. Time to neutrophil recovery/engraftment as well as platelet count recovery appear to be encouraging. HBO therapy resulted in lower EPO serum levels at time of UCB infusion. DisclosuresNo relevant conflicts of interest to declare.

Can initial lactate levels predict the severity of unintentional carbon monoxide poisoning?

Accidental carbon monoxide (CO) intoxication is a major cause of unintentional poisoning. This study aimed to determine the value of initial lactate levels in patients with CO poisoning and to evaluate its utilization in the emergency department (ED). A retrospective cross-sectional study was carried out among patients with CO intoxication, who were admitted to the ED between April 1, 2011 and April 1, 2012. The study data were extracted from a hospital database system using International Classification of Diseases-10 diagnosis codes. The patients were analyzed according to lactate levels, carboxyhemoglobin (COHb) levels, electrocardiographic manifestations, and clinical features at admission to the ED. A total of 74 patients with CO poisoning were enrolled in this study. The average COHb value of the patients was 21.5 ± 13.9%. A total of 50 patients (67.6%) received normobaric oxygen treatment and 24 patients (32.4%) received hyperbaric oxygen (HBO) treatment. The patients who received HBO treatment had increased lactate levels compared with patients receiving normobaric oxygen treatment (2.3 mmol/L vs. 1.0 mmol/L, p < 0.001). The lactate levels were positively correlated with COHb values (r = 0.738, p < 0.001). We determined that a lactate level of 1.85 mmol/L has a sensitivity of 70.8% and a specificity of 78.0% to predict the HBO treatment needed in CO poisoning. In evaluating patients with CO poisoning, an initial lactate level could be taken into consideration as an adjunctive parameter of severity, together with the clinical criteria and levels of COHb.

Is centralization in emergency rural medicine always right? Lessons learned from two cases of decompression sickness

The cases of two patients with decompression sickness (DS) are described to add to the discussion about whether centralization, especially when accompanied by air-medical transport, is always justifiable in island emergency medicine. One patient received hyperbaric oxygen (HBO) treatment on another island after island-to-island transfer by boat; the other received HBO treatment on a ship that was anchored, by chance, close to the island where he became ill. Both cases had a good outcome. Island-to-island transport and within-island treatment, rather than island-to-urban-center transport, was effective, indicating that treatment centralization may not be the most effective protocol all cases. A DS treatment strategy is proposed for use in this geographic area; however, DS occurring on remote islands highlights the wider issue of the centralization of health services.

Hyperbaric oxygen and lipid peroxidation after spinal cord injury

Objective To investigate the effects of hyperbaric oxygen (HBO) therapy following spinal cord injury (SCI) and its mechanisms. Methods Thirty Sprague-Dawley rats were randomly divided into two groups after inducing SCI models using a modified version of Allen's method. The HBO group received HBO treatment 2 h after the procedure and were then treated 100 min every day for 5 consecutive days. All the rats were evaluated 1 h before the operation, and 1 h, 10 d and 20 d afterward using BBB scores and inclined plane experiments. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured. At twenty days, all the rats were sacrificed and their spinal cords were examined pathologically using HE staining. Results Average BBB scores and climbing ability in the HBO group were better than in the control group at the 10th and 20th day after the operation. Compared to the control group, SOD increased significantly and MDA decreased significantly in the HBO group at the 2nd and 5th day after the operation. There was less cystic degeneration of the spinal cord in the HBO group. Conclusions HBO demonstrated a positive effect after SCI. Oxygen free radicals might be one of the mechanisms for the better recovery. Key words: Hyperbaric oxygen; Spinal cord injury; Oxygen free radicals

Neuroprotective Effects of Hyperbaric Oxygen Treatment on Traumatic Brain Injury in the Rat

This study was designed to evaluate the potential benefits of hyperbaric oxygen (HBO) in the treatment of traumatic brain injury (TBI). The right cerebral cortex of rats was injured by the impact of a 20-g object dropped from a predetermined height. The rats received HBO treatment at 3 ATA for 60 min after TBI. Neurological behavior score, brain water content, neuronal loss in the hippocampus, and cell apoptosis in brain tissue surrounding the primary injury site were examined to determine brain damage severity. Three and six hours after TBI, HBO-treated rats displayed a significant reduction in brain damage. However, by 12 h after TBI, the efficacy of HBO treatment was considerably attenuated. Furthermore, at 24, 48, and 72 h after TBI, the HBO treatment did not show any notable effects. In contrast, multiple HBO treatments (three or five times in all), even when started 48 h after TBI, remarkably reduced neurology deficit scores and the loss of neuronal numbers in the hippocampus. Although multiple treatments started at 48 h significantly improved neurological behaviors and reduced brain injury, the overall beneficial effects were substantially weaker than those seen after a single treatment at 6 h. These results suggest that: (1) HBO treatment could alleviate brain damage after TBI; (2) a single treatment with HBO has a time limitation of 12 h post-TBI; and (3) multiple HBO treatments have the possibility to extend the post-TBI delivery time window. Therefore, our results clearly suggest the validity of HBO therapy for the treatment of TBI.

Visual pathway lesion and its development during hyperbaric oxygen treatment: A bold‐ fMRI and DTI study

To characterize and evaluate functional and anatomic changes of visual pathway lesions during hyperbaric oxygen (HBO) treatment with blood-oxygenation-level-dependent functional MRI (BOLD-fMRI) and diffusion tensor imaging (DTI). Sixteen patients with visual pathway lesions received HBO treatment. Both BOLD-fMRI and DTI were performed before and after the treatment, while 12 healthy subjects were also studied with 2 examinations as control. The t-tests were used for the comparison of number of activated voxels (AVs) and fractional anisotropy (FA) between the two groups, and within the patient group before and after HBO treatment. Visual acuity of the patient group before and after the treatment was compared using Wilcoxon signed-rank test. Before the treatment, both AVs (P < 0.01) and FA (P < 0.05) in the bilateral cortexes of occipital lobes were significantly less in the patient group than in the control group. After the treatment, both AVs (P < 0.05) and FA (P < 0.05) were significantly increased. Moreover, The FA of 6 patients with lesions in the optical nerve was greater than the FA of the other 10 patients with lesions in the optic radiation (P < 0.05). BOLD-fMRI combined with DTI was useful for the characterization and evaluation of anatomic and functional changes of visual pathway lesions and their development during HBO treatment.

Effect of hyperbaric oxygen on demineralized bone matrix and biphasic calcium phosphate bone substitutes

The aim of this study was to assess the possible effect of hyperbaric oxygen (HBO) on the healing of critical-sized defects that were grafted with demineralized bone matrix (DBM) combined with Pluronic F127 (F127) to form a gel or putty, or a commercially available biphasic calcium phosphate (BCP), mixed either with blood or F127 to form a putty. Twenty New Zealand White rabbits were randomly divided into 2 groups of 10 animals each. Bilateral 15-mm calvarial defects were created in the parietal bones of each animal, resulting in 40 critical-sized defects. Group I defects were grafted with either DBM putty or DBM gel. Group II defects were grafted with either BCP or BCP putty. Five animals from each group received HBO treatment (100% oxygen, at 2.4 ATA) for 90 minutes per day 5 days a week for 4 weeks. The other 5 animals in each group served as a normobaric (NBO) controls, breathing only room air. All animals were humanely killed at 6 weeks. The calvariae were removed and analyzed by micro computed tomography (mCT) and histomorphometry. mCT analysis indicated a higher bone mineral content (BMC, P < .05), bone volume fraction (BVF; P < .001), and bone mineral density (BMD; P < .001) of the defects grafted with BCP rather than DBM. Furthermore, the voxels that were counted as bone had a higher tissue mineral density (TMD) in the BCP- than in the DBM-filled defects (P < .001). Histologically complete bony union over the defects was observed in all specimens. Histomorphometric analysis showed that DBM-filled defects had more new bone (P < .007) and marrow (P < .001), and reduced fibrous tissue compared with the BCP defects (P < .001) under NBO conditions. HBO treatment reduced the amount of fibrous tissue in BCP filled defects (P < .05), approaching levels similar to that in matching DBM-filled defects. HBO also resulted in a small but significant increase in new bone in DBM-grafted defects (P < .05). Use of DBM or BCP promoted healing in these critical-sized defects. Hyperbaric oxygen therapy resulted in a slight increase in new bone in DBM-grafted defects and much larger reduction in fibrous tissue and matching increases in marrow in BCP-grafted defects, possibly through increased promotion of angiogenesis.

Effect of hyperbaric oxygen on grafted and nongrafted calvarial critical-sized defects

This study was undertaken to evaluate the effect of hyperbaric oxygen (HBO) on the repair of critical-sized defects in the presence and absence of a nonvascularized autogenous bone graft. Ten New Zealand White rabbits were randomly divided into 2 groups of 5 animals each. Bilateral 15-mm calvarial defects were created in the parietal bones of each animal, resulting in 20 critical-sized defects. Autogenous bone grafts (ABG) were allocated to the left or right defect of each animal. Group 1 received HBO treatment at 2.4 ATA 100% oxygen for 90 minutes per day 5 days a week for 4 weeks. Group 2 served as a normobaric (NBO) control, breathing only room air. The animals in each group were humanely killed at 6 weeks. Calvaria were analyzed by micro-CT and histomorphometry. Micro-CT analysis indicated that as expected there was a higher bone mineral density (BMD) and bone mineral content (BMC) in ABG than unfilled defects (P < .05). However, there was a significant decline in the bone mineral content (BMC) of HBO-treated grafted defects compared to NBO-treated grafted defects (P < .05). Histologically complete bridging of the defect was observed in both NBO and HBO ABG grafted defects. Histomorphometic analysis showed that HBO treatment increased new bone and marrow, and reduced fibrous tissue in the defects (P < .01 for all). Examination of residual graft showed a near significant reduction in residual graft volume (11.2 +/- 4.7 versus 19.1 +/- 7.7, HBO versus NBO P = .085) in the HBO group. The use of a graft increased new bone and marrow in the NBO group (P < .001 for both); however, in the HBO-treated animals the differences between grafted and ungrafted were not significant. HBO enhances bony healing in ungrafted rabbit calvarial critical-sized defects and may increase the rate of residual graft resorption in autogenous bone-grafted defects.

Hyperbaric oxygen therapy in the pediatric patient: the experience of the Israel Naval Medical Institute.

The pediatric patient is to be found in hyperbaric facilities throughout the world, receiving hyperbaric oxygen (HBO) therapy for both life-threatening and chronic diseases. To review the experience accumulated at the Israel Naval Medical Institute in the treatment of pediatric patients. A retrospective analysis and review of all records of patients younger than age 18 years. Between 1980 and 1997, 139 pediatric patients age 2 months to 18 years (mean, 7.7 years) received HBO treatment at the Israel Naval Medical Institute. Of the children, 111 (79%) suffered from acute carbon monoxide (CO) poisoning; 13 (9.2%) were treated after crush injury, traumatic ischemia, or compartment syndrome; 4 (2.8%) had clostridial myonecrosis; 1 (0.7%) had necrotizing fasciitis; 5 (3.6%) had refractory osteomyelitis; 2 (1.4%) had suffered massive air embolism; 2 (1.4%) had purpura fulminans; and 1 (0.7%) suffered from decompression sickness. Outcome, judged by neurologic sequelae, mortality, and extent of soft tissue loss and limb amputation, was favorable in 129 patients (93%). Two patients (1.4%) died, 1 as a result of CO poisoning and the other, gas gangrene; 2 of the patients in the CO group (1.4%) remained with neurologic sequelae, and 6 patients in the acute traumatic ischemia group (4.3%) underwent limb amputation. We had a favorable experience with 129 of a total 139 pediatric patients treated at our facility for the indications listed. A basic knowledge of HBO therapy is needed to refer the pediatric patient for treatment when indicated. The needs of the pediatric patient, especially the critically ill, require specific skills and equipment inside the hyperbaric chamber. Close collaboration between the pediatrician and the hyperbaric medicine physician is essential to ensure adequate care for infants and children.

Hyperbaric oxygen therapy and free radical production: an experimental study in doxorubicin (Adriamycin) extravasation injuries.

The role of hyperbaric oxygen (HBO) therapy in free radical-mediated tissue injury is not clear. HBO has been shown to enhance the antioxidative defense mechanisms in some animal studies, but HBO has also been reported to increase the production of oxygen free radicals. To investigate this controversy, we studied the effect of HBO in a doxorubicin (Adriamycin) extravasation model, because the cytotoxic activity of doxorubicin is partly related to its quinone structure, which leads to the formation of cytotoxic oxygen intermediates. Fifty-four Sprague-Dawley rats underwent injection of 0.3 ml doxorubicin solution (2 mg per milliliter) intradermally on both flanks as described by Rudolph and colleagues. Group I (N = 28) received HBO treatment (2 hours at 2 ATA) for 3 days prior to injection and 7 days postinjection. Group II (N = 26) received no HBO treatment. At 2, 3, and 5 weeks, the size of the ulcers and the surrounding area of alopecia in group I (+HBO) were significantly larger than in group II (-HBO): 112.2 mm2 vs. 42.8 mm2 (p < 0.01) and 1,132.2 mm2 vs. 364.8 mm2 (p < 0.005). Biochemical analysis of the biopsied skin ulcers, to measure the parameters of oxygen free radical production, indicated (similar) low levels of xanthine oxidase for both groups. However, significantly elevated levels of malonyldialdehyde (MDA), indirect evidence of free radical production, was observed in group I (+HBO) in comparison with group II (-HBO): 36.58 vs. 5.84 ng per minute per milligram protein (p < 0.001), which might indicate free radical-induced cellular injury. It is concluded that in this animal study the cytotoxicity of doxorubicin is potentiated by HBO therapy. The elevated levels of MDA suggest a direct additive cytotoxic effect by increased membrane lipid peroxidation. HBO therapy, therefore, might be deleterious in the early (preulcer) stage of doxorubicin extravasation.