Early Hyperbaric Oxygen Treatment Research Articles

ROS exhaustion reverses the effects of hyperbaric oxygen on hemorrhagic transformation through reactivating microglia in post-stroke hyperglycemic mice

Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-l-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.

Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes. Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury. One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05. In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.

80 Early Hyperbaric Oxygen Treatment Attenuates Burn-Induced Neuroinflammation by Inhibiting the Galectin-3-Dependent Toll-Like Receptor-4 Pathway

80 Early Hyperbaric Oxygen Treatment Attenuates Burn-Induced Neuroinflammation by Inhibiting the Galectin-3-Dependent Toll-Like Receptor-4 Pathway

Early Hyperbaric Oxygen Treatment Attenuates Burn-Induced Neuroinflammation by Inhibiting the Galectin-3-Dependent Toll-Like Receptor-4 Pathway in a Rat Model.

Hyperbaric oxygen (HBO) treatment has been proven to decrease neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague-Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment; (2) sham burn with HBO treatment; (3) burn with one-week sham HBO treatment; (4) burn with two-week sham HBO treatment; (5) burn with one-week HBO treatment; and (6) burn with two-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting. A behavior test was also conducted, which revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared to the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor α (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis showed that the expression of Gal-3, TLR-4, CD68 and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia and macrophage activation in a rat model.

The analgesic effect of early hyperbaric oxygen treatment in chronic constriction injury rats and its influence on nNOS and iNOS expression and inflammatory factor production.

ObjectiveTo observe the analgesic effect of early hyperbaric oxygen (HBO) treatment in chronic constriction injury (CCI) rats, and to analyze the influence of HBO on the expression of neuronal nitric oxide synthase and inducible nitric oxide synthase and on the levels of inflammatory factors.MethodsRats were assigned into three groups randomly: sham, CCI, and HBO groups. The CCI rat model was established, and HBO treatment at 2.5 ATA (60 min) was given one day after surgery, lasting for five consecutive days. The pain behaviors of the rats were observed at predetermined time points, and the activation of astrocytes at dorsal horns as well as the changes of the synaptic ultrastructures were observed. The expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were detected by Western blot, and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were detected by quantitative real-time PCR.ResultsRats in the CCI group developed hyperalgesia when compared with the sham group. Mechanical withdrawal threshold decreased and thermal withdrawal latency shortened in CCI group. Also, astrocytes at the dorsal horn were activated, the synaptic structure was disordered, the expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were increased significantly, and the release of inflammatory factor (TNF-α and IL-1β) was up-regulated. However, with early initiation of HBO treatment, rats in the HBO group showed significantly alleviated hyperalgesia, increased mechanical withdrawal threshold, and prolonged thermal withdrawal latency. HBO treatment inhibited astrocyte expression and maintained normal synaptic structure. The expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were decreased in the dorsal horn, and the release of inflammatory factor (TNF-α and IL-1β) was reduced.ConclusionsEarly HBO treatment significantly improves hyperalgesia in rats with neuropathic pain. The decreased expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase and reduced levels of inflammatory factors are important mechanisms by which early HBO helps to alleviate neuropathic pain.

The NO-cGMP-PKG signal transduction pathway is involved in the analgesic effect of early hyperbaric oxygen treatment of neuropathic pain

BackgroundHyperbaric oxygen (HBO) has the potential to relieve neuropathic pain. The purpose of this study was to determine whether the NO-cGMP-PKG signaling pathway is involved in the analgesic effects of early hyperbaric oxygen treatment of neuropathic pain in rats.MethodsRats were randomly grouped for establishment of chronic constriction injury (CCI) models. Intrathecal catheters were inserted and 2.5ATA HBO therapy was administered from day 1 post-surgery for 60 minutes daily, continuously for 5 days; menstruum NS, DMSO, NO synthase(NOS) nonspecific inhibitor (L-NAME), soluble guanylyl cyclase(sGC) inhibitor (ODQ) and protein kinase G(PKG) inhibitor (KT5823) were administered intrathecally 30 minutes prior to HBO therapy. Pain-related behaviors in rats were observed at specific time points. Western blot and real-time RT-PCR were used to observe the expressions of PKG1 mRNA and protein in the spinal dorsal horn.ResultsCompared with the CCI group, HBO could significantly relieve mechanical and thermal hyperalgesia in rats. After intrathecal administration of L-NAME, ODQ and KT5823, effects of HBO on relieving hyperalgesia in rats were reversed (P < 0.05 vs. HBO), and expression of PKG1 mRNA and protein decreased in the spinal dorsal horn of the animals (P < 0.05 vs. HBO).ConclusionsEarly HBO therapy could significantly improve symptoms of hyperalgesia of neuropathic pain in rats, possibly via activation of the NO-cGMP-PKG signaling transduction pathway.

Hyperbaric Oxygen Therapy Alleviates Carbon Monoxide Poisoning-Induced Delayed Memory Impairment by Preserving Brain-Derived Neurotrophic Factor-Dependent Hippocampal Neurogenesis.

To test the hypothesis that hyperbaric oxygen therapy ameliorates delayed cognitive impairment after acute carbon monoxide poisoning by promoting neurogenesis through upregulating the brain-derived neurotrophic factor in the hippocampus. Laboratory animal experiments. University/Medical center research laboratory. Adult, male Sprague-Dawley rats. Rats were divided into five groups: (1) non-carbon monoxide-treated control, (2) acute carbon monoxide poisoning, (3) acute carbon monoxide poisoning followed by 7-day hyperbaric oxygen treatment, (4) carbon monoxide + hyperbaric oxygen with additional intracerebroventricular infusion of Fc fragment of tyrosine kinase receptor B protein (TrkB-Fc) chimera, and (5) acute carbon monoxide poisoning followed by intracerebroventricular infusion of brain-derived neurotrophic factor. Acute carbon monoxide poisoning was achieved by exposing the rats to carbon monoxide at 2,500 ppm for 40 minutes, followed by 3,000 ppm for 20 minutes. Hyperbaric oxygen therapy (at 2.5 atmospheres absolute with 100% oxygen for 60 min) was conducted during the first 7 days after carbon monoxide poisoning. Recombinant human TrkB-Fc chimera or brain-derived neurotrophic factor was infused into the lateral ventricle via the implanted osmotic minipump. For labeling of mitotic cells in the hippocampus, bromodeoxyuridine was injected into the peritoneal cavity. Distribution of bromodeoxyuridine and two additional adult neurogenesis markers, Ki-67 and doublecortin, in the hippocampus was evaluated by immunohistochemistry or immunofluorescence staining. Tissue level of brain-derived neurotrophic factor was assessed by enzyme-linked immunosorbent assay. Cognitive behavior was evaluated by the use of eight-arm radial maze. Acute carbon monoxide poisoning significantly suppressed adult hippocampal neurogenesis evident by the reduction in number of bromodeoxyuridine-positive, Ki-67⁺, and doublecortin⁺ cells in the subgranular zone of the dentate gyrus. This suppression of adult neurogenesis by the carbon monoxide poisoning was appreciably alleviated by early treatment of hyperbaric oxygen. The hyperbaric oxygen treatment also promoted a sustained increase in hippocampal brain-derived neurotrophic factor level. Blockade of hippocampal brain-derived neurotrophic factor signaling with intracerebroventricular infusion of recombinant human TrkB-Fc chimera significantly blunted the protection by the hyperbaric oxygen on hippocampal neurogenesis; whereas intracerebroventricular infusion of brain-derived neurotrophic factor mimicked the action of hyperbaric oxygen and preserved hippocampal neurogenesis after acute carbon monoxide poisoning. Furthermore, acute carbon monoxide poisoning resulted in a delayed impairment of cognitive function. The hyperbaric oxygen treatment notably restored the cognitive impairment in a brain-derived neurotrophic factor-dependent manner. The early hyperbaric oxygen treatment may alleviate delayed memory impairment after acute carbon monoxide poisoning by preserving adult neurogenesis via an increase in hippocampal brain-derived neurotrophic factor content.

Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

IntroductionIntracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH.MethodsMinipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH.ResultsHigh-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated.ConclusionsThe data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

Hyperbaric oxygen treatment at various stages following chronic constriction injury produces different antinociceptive effects via regulation of P2X4R expression and apoptosis.

PurposeThe aims of this study were to investigate the effect of hyperbaric oxygen (HBO) treatment at various stages following chronic constriction injury (CCI) and to explore the underlying mechanisms of HBO treatment.MethodsForty adult male Sprague—Dawley rats were randomly assigned to five groups (n = 8 for each group): the sham group, CCI group, HBO1 group, HBO2 group, and HBO3 group. Neuropathic pain was induced by CCI of the sciatic nerve. HBO treatment began on postoperative days 1, 6, and 11 and continued for 5 days. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. The expression of P2X4R was determined by immunohistochemistry and western blot analysis. Cell apoptosis was measured using TUNEL staining. The expression of caspase 3 was measured using reverse transcription polymerase chain reaction (RT-PCR). Electron microscopy was used to determine the ultrastructural changes.ResultsEarly HBO treatment beginning on postoperative day 1 produced a persistent antinociceptive effect and inhibited the CCI-induced increase in the expression of P2X4R without changing CCI-induced apoptosis. In contrast, late HBO treatment beginning on postoperative day 11 produced a persistent antinociceptive effect and inhibited CCI-induced apoptosis and upregulation of caspase-3 without changing the expression of P2X4R. In addition, late HBO treatment reduced CCI-induced ultrastructural damage. However, HBO treatment beginning on postoperative day 6 produced a transient antinociceptive effect without changing the expression of P2X4R or CCI-induced apoptosis.ConclusionHBO treatment at various stages following CCI can produce antinociceptive effects via different mechanisms. Early HBO treatment is associated with inhibition of P2X4R expression, and late HBO treatment is associated with inhibition of cell apoptosis.

Hyperbaric oxygen treatment in the experimental spinal cord injury model

Background contextSpinal cord trauma is a major cause of mortality and morbidity. Although no known treatment for spinal cord injury exists, a limited number of effective treatment modalities and procedures are available that improve secondary injury. Hyperbaric oxygen (HBO) treatment has been used to assist in neurologic recovery after cranial injury or ischemic stroke. PurposeTo report the findings on the effectiveness of HBO treatment on rats with experimental traumatic spinal cord injury. Improvement was evaluated through motor strength assessment and nitrite level assay testing. Study designWe randomly distributed 40 rats among 5 groups of 8 rats each: sham incurable trauma, induced trauma, HBO treatment begun at the 1st hour, HBO treatment begun at the 6th hour, and HBO treatment begun at the 24th hour. MethodThe HBO treatment was administered to rats in three of the groups and conducted in two 90-minute sessions, under an absolute atmospheric pressure of 2.4 at 100% oxygen for 5 days. In the motor strength evaluations, all the rats were observed during the inclined plane test and clinical motor examination on the first, third, and fifth days. In addition, the nitrite levels of spinal cord tissues on the sixth day were also studied. ResultsResults from the inclined plane levels and motor strength test from all the three groups undergoing HBO treatment were higher than those from Group 2. It was also determined that early HBO treatment resulted in higher recovery rates (groups 3 and 4). The highest levels were seen in the group in which the HBO treatments were started in the first hour (Group 3). It was noted that nitrite levels of rats in the group exposed to trauma increased, compared with the sham group, but increased levels also diminished after HBO treatments. Again, the greatest decrease in nitrite levels was evident in the group where the HBO treatment was started the earliest (Group 3). ConclusionsPrompt HBO treatment after trauma significantly contributed to the clinical, histopathologic, and biochemical recovery of the rats.

Effects of very early hyperbaric oxygen treatment on patients with malignant brain edema after surgical operation for severe traumatic brain injury

Objective To investigate effects of very early hyperbaric oxygen treatment (HBOT) on patients with malignant brain edema after surgical operation for treatment of severe traumatic brain injury (TBI).Methods A total of 146 patients who suffered from malignant brain edema after last surgical operation for severe TBI were enrolled for this study.According to the intervention time of HBOT,they were randomized into a very early group (HBOT within 3 days after operation,n =55),an ordinary group (HBOT at 4 to 10 days after operation,n =65) and a control group (non-HBOT,n =26).Mortality rate of the 3 groups were recorded within 4 weeks after operation,and GCS (Glasgow Coma Scale) score were assessed in 1,2,3 and 4 weeks after operation.Dynamic head CT scan were performed for detecting brain status and for determine the duration of brain edema.Results The mortality of the very early group,the ordinary group and the control group were 10.9％,7.7％ and 11.5％,respectively,and no statistically significant difference was revealed among the groups (P ＞ 0.05).In very early group,the GCS scores of 1,2,3 and 4 weeks after operation were (8.837 ±3.350),(10.755 ± 3.388),(11.633 ± 3.408) and (12.367 ± 3.408),respectively,with significant difference between the time points 1 week and 2,3 and 4 weeks as well as 2 and 4 weeks after surgery (P ＜0.05),but not between 2 and 3 as well as 3 and 4 weeks after surgery (P ＞ 0.05).In ordinary group,the GCS scores at 1,2,3 and 4 weeks after surgery were (8.509 ±3.042),(9.458 ±3.115),(10.186 ±3.203) and (10.627 ±3.439),respectively,with significant difference between 1 week and 2,3 and 4 weeks after operation (P ＜ 0.05).In control group,the GCS scores at 1,2,3 and4 weeks after surgery were (8.042 ±2.881),(8.417 ±2.962),(8.542 ±3.02) and (8.958 ± 3.043),with no statistical difference among different time points (P ＞ 0.05).When compared with the very early group,the GCS sores of the ordinary group and the control group were significantly lower after intervention (P ＜ 0.05),and the GCS of control group was lower than that of the ordinary group (P ＜ 0.05).As for brain edema duration,the very early group was the shortest among the 3 groups (P ＞ 0.05) Conclusion Very early hyperbaric oxygen treatment could improve consciousness state and alleviate malignant brain edema after surgical operation in TBI patients. Key words: Severe traumatic brain injury; Hyperbaric oxygen treatment; Glasgow coma scale score; Brain edema

Early Hyperbaric Oxygen Treatment for Nonarteritic Central Retinal Artery Obstruction

To compare hyperbaric oxygen treatment combined with hemodilution with hemodilution only in central retinal artery obstruction. Retrospective, nonrandomized case series. We reviewed records of all our patients diagnosed with central retinal artery obstruction between 1997 and 2010. In these patients, hyperbaric oxygen and hemodilution therapy had been administered routinely (oxygen group). Where hyperbaric oxygenation could not be performed, patients were underwent hemodilution only (control group). Patients with presenting visual acuity (VA) of up to 20/200 within 12 hours of onset were included in our analysis. Exclusion criteria included cilioretinal vessels or arteritic occlusion. The oxygen group comprised 51 patients, and the control group comprised 29 patients. Mean baseline VA was counting fingers (oxygen group) and 20/1000 (control group; P = .1). Most other potential confounders, including duration of symptoms, also did not differ significantly at baseline. In the oxygen group, mean VA improvement was 3 lines (P < .0001). This was sustained over a follow-up of 3 months (P = .01). In the control group, mean improvement was 1 line (P = .23 at discharge, P = .17 at follow-up). Differences between both groups were not significant (P = .07 at discharge, P = .26 at follow-up). The number of patients gaining 3 lines or more was 38.0% versus 17.9% at discharge (P = .06) and 35.7% versus 30.8% at follow-up (P = .76). We saw significant VA improvement after the combined treatment, but not when using hemodilution only. Confirming superiority of the combination treatment requires a randomized, prospective trial. A high number of nonresponders highlights the need to improve our understanding and treatment of hypoxia-related metabolic insults after central retinal artery obstruction.

Assessment of HBO early intervention in hypoxic ischemic encephalopathy

Objective This study aimed to explore the curative effect of hyperbaric oxygen (HBO)for neonatal hypoxic-ischemie eneephalopathy(HIE).Methods New born cases diagnosed with HIE were collected from Jan.2008 to Oct.2010.Peabody Developmental Motor Scale-2 was used to evaluate the effect before and after HBO treatment.Among the 341 cases enrolled in the study,all cases were undergone therapy according to the guideline of HIE.Patients were divided into control group(179cases)and treatment group(162eases).Results GMQ and TMQ scores of treatment group after treatment were(84.2±19.6)and(85.1±21.2); while the control group's were(79.7±18.2)and(80.6±19.2).what's more.treatment group had fewer patients got complications than control group.There was significant differences between the two groups(P＜0.05).Conclusion Early HBO treatment of HIE has significant curative effect.It has to further confirm the conditions of patients to reduce the possible complications during HBO treatment. Key words: Hypoxic-ischemic encephalopathy; Hyperbaric oxygen; Complication

Hyperbaric oxygen treatment attenuated the decrease in regional glucose metabolism of rats subjected to focal cerebral ischemia: A high resolution positron emission tomography study

Cerebral hypoxia may be the main component of cell damage caused by ischemia. Previous studies demonstrated a neuroprotective effect of early hyperbaric oxygen (HBO) treatment in various animal models of focal cerebral ischemia. Neuropathologic study showed that exposure of HBO may prevent cell death in ischemic cortex. In the present study, we aimed to assess cellular function of ischemic rat brain after HBO treatment by means of a high-resolution positron emission tomography scanner (microPET) used specifically for small animal imaging. The male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO), with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. One hour after ischemia, HBO therapy (3 atm absolute, 1 h) was initiated. Local cerebral glucose utilization in the ischemic area was measured before, 1 h and 3 h after ischemia, with 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) as a tracer. Neurological deficits and infarct volumes were assessed at 24 h after ischemia. Our study showed that early HBO therapy significantly reduced infarct volume of brain 24 h after ischemia. Moreover, glucose utilization in the ischemic area underwent a severe decrease during 1–3 h after MCAO, while the early HBO treatment significantly attenuated the decrease in cerebral metabolic rate of glucose in the ischemic core of the cortex compared with controls. We report for the first time the application of microPET to quantify the rates of glucose metabolism in the ischemic core of rats exposed to HBO. Our results suggest that the early exposure of HBO can partially reverse the downward trend for glucose utilization in the ischemic core, which might contribute to the reported beneficial effects of early HBO therapy on permanent cerebral ischemia.

Reduced infarct volume and differential effects on glial cell activation after hyperbaric oxygen treatment in rat permanent focal cerebral ischaemia

Permanent middle cerebral artery occlusion (MCAO) causes neurodegeneration and a robust activation of glial cells primarily in sensorimotor brain regions of rats. It has been shown that hyperbaric oxygen (HBO) increases oxygen supply to ischaemic areas and reduces neuronal cell loss. The effects of HBO treatment on microgliosis and astrogliosis in permanent cerebral ischaemia have not been addressed so far, but might be critical for neurodegeneration and neuroprotection, respectively. Therefore, we used spontaneously hypertensive rats with permanent MCAO to investigate the time window to start HBO and to compare the effects of different HBO treatment frequencies on infarct volume and on differences with regard to microgliosis and astrogliosis. Seven days after MCAO the infarct volume was calculated from Nissl-stained brain sections by image analysis. HBO significantly decreased the infarct volume when used as early as 15, 90 or 180 min post-MCAO by 24%, 16% and 13%, respectively, in the single-treatment group. Repetitive HBO treatment (first HBO session 90 min after MCAO) was not effective. Microglial cells and astrocytes were detected by cytochemical fluorescent labelling and confocal laser scanning microscopy. In the single-treatment group we observed significantly higher astrocyte immunoreactivity but decreased microglial density in the peri-infarct region. These effects of HBO treatment on glial cells were not present in rats where HBO did not reduce the infarct volume (360 min after MCAO). Our data indicate that HBO-induced suppression of microgliosis and aggravated response of astrocytes might contribute to the reported beneficial effects of early HBO treatment in cerebral ischaemia.

Effects of hyperbaric oxygen on GDNF expression and apoptosis in spinal cord injury

The effects of hyperbaric oxygen treatment on the progress of secondary damage following traumatic spinal cord injury were investigated. The early onset of hyperbaric oxygen treatment significantly diminished the number of apoptotic cells 1 day after the injury. However, hyperbaric oxygen did not influence the proliferation of macrophages or activated microglia. The gene expression of glial cell line-derived neurotrophic factor (GDNF) and inducible nitric oxide synthetase (iNOS) was significantly attenuated 1 day after the injury in the hyperbaric oxygen groups compared with the control group. The down-regulation was confirmed by immunohistochemical staining. Early hyperbaric oxygen treatment was shown to effectively suppress the progress of apoptosis perhaps via the inhibition of iNOS gene despite the down-regulation of the GDNF gene.