Hyperbaric oxygen treatment in delayed post-hypoxic encephalopathy following inhalation of liquefied petroleum gas: a case report.

Delayed post-hypoxic encephalopathy can occur after an episode of anoxia or hypoxia. Symptoms include apathy, confusion, and neurological deficits. We describe a 47-year-old male patient who inhaled gas from a kitchen stove liquid petroleum gas cylinder. He was diagnosed with hypoxic ischaemic encephalopathy 12 hours after his emergency department admission. He received six sessions of hyperbaric oxygen treatment (HBOT) and was discharged in a healthy state after six days. Fifteen days later, he experienced weakness, loss of appetite, forgetfulness, depression, balance problems, and inability to perform self-care. One week later, he developed urinary and fecal incontinence and was diagnosed with post-hypoxic encephalopathy. After 45 days from the onset of symptoms, he was referred to the Underwater and Hyperbaric Medicine Department for HBOT. The patient exhibited poor self-care and slow speech rate, as well as ataxic gait and dysdiadochokinesia. Hyperbaric oxygen was administered for twenty-four sessions, which significantly improved the patient's neurological status with only hypoesthesia in the left hand remaining at the end of treatment. Hyperbaric oxygen has been reported as successful in treating some cases of delayed neurological sequelae following CO intoxication. It is possible that HBO therapy may also be effective in delayed post-hypoxic encephalopathy from other causes. This may be achieved through mechanisms such as transfer of functional mitochondria to the injury site, remyelination of damaged neurons, angiogenesis and neurogenesis, production of anti-inflammatory cytokines, and balancing of inflammatory and anti-inflammatory cytokines.

Curcumin protects against cognitive impairments in a rat model of chronic cerebral hypoperfusion combined with diabetes mellitus by suppressing neuroinflammation, apoptosis, and pyroptosis.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is regarded as a high-risk factor for cognitive decline in vascular dementia (VaD). We have previously shown that diabetes mellitus (DM) synergistically promotes CCH-induced cognitive dysfunction via exacerbating neuroinflammation. Furthermore, curcumin has been shown to exhibit anti-inflammatory and neuroprotective activities. However, the effects of curcumin on CCH-induced cognitive impairments in DM have remained unknown. METHODS: Rats were fed with a high-fat diet (HFD) and injected with low-dose streptozotocin (STZ), followed by bilateral common carotid artery occlusion (BCCAO), to model DM and CCH in vivo. After BCCAO, curcumin (50 mg/kg) was administered intraperitoneally every two days for eight weeks to evaluate its therapeutic effects. Additionally, mouse BV2 microglial cells were exposed to hypoxia and high glucose to model CCH and DM pathologies in vitro. RESULTS: Curcumin treatment significantly improved DM/CCH-induced cognitive deficits and attenuated neuronal cell death. Molecular analysis revealed that curcumin exerted protective effects via suppressing neuroinflammation induced by microglial activation, regulating the triggering receptor expressed on myeloid cells 2 (TREM2)/toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway, alleviating apoptosis, and reducing nod-like receptor protein 3 (NLRP3)-dependent pyroptosis. CONCLUSIONS: Taken together, our findings suggest that curcumin represents a promising therapy for DM/CCH-induced cognitive impairments.

Hyperbaric oxygen therapy in acute stroke: is it time for Justitia to open her eyes?

Hypoxia is a critical component of neuronal death in patients with stroke. Therefore increasing oxygenation of brain tissue seems to be a logical therapy against cerebral ischemia. Oxygen therapy exists in two modalities: normobaric hyperoxia therapy and hyperbaric oxygen therapy (HBO). HBO is a therapeutic procedure in which pure (100%) oxygen is administered at greater than atmospheric pressure in HBO therapy chambers. In this review article, we aimed to summarize the current knowledge regarding the therapeutic use of HBO in acute stroke patients. Literature review and electronic search were performed using PubMed, Medscape, and UpToDate with the keywords stroke, acute stroke, hyperbaric oxygen therapy, and hyperoxia. According to the reviewed literature, the use of HBO as routine stroke therapy cannot be justified in acute stage of stroke. More randomized, controlled studies are needed regarding safety and especially effectives of HBO in stroke patients. Also, standardized definitionof HBO should be proposed and used in all future studies.

Hyperbaric oxygen preconditioning ameliorates hypoxia-ischemia brain damage by activating Nrf2 expression in vivo and in vitro.

The present study aimed to investigate whether hyperbaric oxygen preconditioning (HBO-PC) could ameliorate hypoxia-ischemia brain damage (HIBD) by an increase of Nrf2 expression. P7 Sprague-Dawley rats (aged 7 d, n = 195) were used in two in vivo experiments, including BO-PC exposure experiments in non-HIBD models and treatment experiments in HIBD models. 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl Staining, and TUNEL staining were performed. And expressions of Nrf2, HO-1, and GSTs were measured. For in vitro studies, oxygen-glucose deprivation cells were established. Morphological and apoptotic staining and gene silencing of Nrf2 by siRNA transfection were investigated. For exposure experiments, HBO-PC for longer time increased the expression of Nrf2 significantly. And for treatment experiments, HBO-PC treatment significantly decreased infarction area, lessened neuronal injury, reduced apoptosis, and increased both the expression of Nrf2 and activities of its downstream proteins. Cytology tests confirmed effects of HBO-PC treatments. Besides, Nrf2 siRNA significantly reduced protective effects of HBO-PC. These observations demonstrated that an up-regulation of Nrf2 by HBO-PC might play an important role in the generation of tolerance against HIBD.

Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage.

PURPOSE: Cognitive impairment may occur in 42-50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury.The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. METHODS: Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. RESULTS: The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5-7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. CONCLUSIONS: Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event.

[Beneficial effect of preferred music on cognitive functions in minimally conscious state patients]. / Effets bénéfiques de la musique préférée sur les capacités cognitives des patients en état de conscience minimale.

Several studies have shown that music can boost cognitive functions in normal and brain-damaged subjects. A few studies have suggested a beneficial effect of music in patients with a disorder of consciousness but it is difficult to conclude since they did not use quantified measures and a control condition/group. The aim of the present study was to compare the effect of music to that of a continuous sound on the relational behavior of patients in a minimally conscious state (MCS). Behavioral responses of six MCS patients were evaluated using items from the Coma Recovery Scale-Revised. Weekly evaluation sessions were carried out, over four weeks, under two conditions: following the presentation of either the patient's preferred music, or following a continuous sound (control condition). Qualitative and quantitative analyses showed that twelve of the eighteen sessions (66.6%) showed a better result for the music condition than for the control condition. This new protocol suggests that preferred music has a beneficial effect on the cognitive abilities of MCS patients. The results further suggest that cerebral plasticity may be enhanced in autobiographical (emotional and familiar) contexts. These findings should now be further extended with an increased number of patients to further validate the hypothesis of the beneficial effect of music on cognitive recovery.

Bilateral supratentorial epidural hematomas: a rare complication in adolescent spine surgery.

A 14-year-old girl presented with a rare case of spontaneous bilateral supratentorial epidural hematomas which developed rapidly following cervical surgery. The hematomas presumably resulted from dural dynamics changes secondary to cerebrospinal fluid loss and intracranial hypotension. Intracranial epidural hemorrhage after spinal surgery is extremely uncommon with only one previous case report. Spontaneous intracranial epidural hematoma is an extremely rare complication, but should be considered as a possible complication of spine surgery, especially in adolescents complicated by delayed consciousness and breathing restoration from anesthesia. This case report expands the presently known clinical spectrum of this uncommon complication.

Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia.

Tissue hypoxia may play an important role in the development of ischemic brain damage. In the present study we investigated in a rat model of transient focal brain ischemia the neuroprotective effects of increasing the blood oxygen transport capacity by applying a semifluorinated alkane (SFA)-containing emulsion together with normobaric hyperoxygenation (NBO). The spread of tissue hypoxia was studied using pimonidazole given prior to filament-induced middle cerebral artery occlusion (MCAO, 2 h). Treatment consisted of intravenous injection of saline or the SFA-containing emulsion (0.5 or 1.0 ml/100g body weight; [SFA(0.5) or SFA(1.0)]) either upon establishing MCAO (early treatment) or after filament removal (delayed treatment). After injection NBO was administered for 8 h (early treatment) or 6 h (delayed treatment). Experiments were terminated 8 or 24 h after MCAO. In serial brain sections tissue hypoxia and irreversible cell damage were quantitatively determined. Furthermore, we studied hypoxia-related gene expression (VEGF, flt-1). Early treatment significantly (p<0.05) reduced the volumes of tissue damage (8 h after MCAO: SFA(1.0), 57±34 mm³; controls, 217±70 mm³; 24 h after MCAO: SFA(1.0), 189±82 mm³; controls, 317±60 mm³) and of P-Add immunoreactivity (8 h after MCAO: SFA(1.0), 261±37 mm³; controls, 339±26 mm³; 24h after MCAO: SFA(1.0), 274±47 mm³; controls, 364±46 mm³). Delayed treatment was comparably successful. The volume of the hypoxic penumbra was not decreased by the treatment. Similarly, VEGF and flt-1 mRNA levels did not differ between the experimental groups. From these data we conclude that increasing the blood oxygen transport capacity in the plasma compartment provides a neuroprotective effect by alleviating the severity of hypoxia to a level sufficient to prevent cells from transition into irreversible damage.

One- and three-time mild hypobaric hypoxia modifies expression of mitochondrial thioredoxin-2 in hippocampus of rat.

Our previous study demonstrated that preconditioning by 3-times repetitive mild hypoxia significantly augmented expression of mitochondrial thioredoxin-2 (Trx-2) at 3 h after subsequent acute severe hypoxia in rat hippocampus. However, it was unclear whether this augmentation was due to build up of Trx-2 by mild hypoxia before severe hypoxia or by modification of reaction to severe hypoxia itself. To answer on this question we study the expression level during and after preconditioning without subsequent severe hypoxia. Trx-2 expression was studied by immunocytochemistry 3 h and 24 h after first session and 3 h and 24 h after last session of 3-times (spaced at 24 h) mild hypobaric hypoxia (360 Torr, 2h). At 3 h after 1-time hypoxia (first session of 3-time hypoxia) the total number of Trx-2-immunoreactive cells (Nt) was significantly decreased in contrast with control in CA2, CA3 and DG. The number of cells with intensive expression of Trx-2 (Ni) was reduced in CA1 and CA3. At 24 h after the same 1-time hypoxia Nt was lower than in control and at 3 h time-point in all hippocampal areas studied (CA1, CA2, CA3 and DG); Ni was decreased only compared to control in CA1 and CA3. At 3 h after last session of 3-times hypoxia Nt and Ni were significantly down regulated in comparison with control only in CA1. At 24 h after it Nt was significantly decreased compared to control in CA1, CA2 and CA3 (in DG the decrease was not statistically significant) but in all areas was higher than at 24 h after 1-time hypoxia. Dynamics of Nt changes from 3-hours after single to 24-hours after triple moderate hypoxia had the wave phase character. These findings indicate that Trx-2 expression in most areas of hippocampus was decreased to 24 h after 3-time mild hypoxia. Thus the augmentation of Trx-2 expression in hippocampal neurons of preconditioned animals in response to subsequent severe hypoxia is caused obviously not by Trx-2 accumulation during preconditioning sessions but by modification of reaction to severe impact.

[Recovery of consciousness by electrical dorsal column stimulation in brain injury patients].

Treatment with electrical dorsal column stimulation was performed in 7 cases of diffuse axonal injury, 2 cases of brain contusion and 1 case of hypoxic diffuse brain damage. After inadequate response to various treatment modalities, each patient was implanted with a spinal cord stimulation system. The effectiveness was assessed using a standard scoring system which consisted of state scale and reaction scale (the society for treatment of coma). Both state scale and reaction scale were considered to improve in 4 patients after dorsal column stimulation. In 5 patients, the effectiveness of dorsal column stimulation could not be distinguished from natural improvement. One patient of hypoxic brain damage showed slight deterioration after the dorsal column stimulation. Among the state scale, significant improvement was found in spontaneous movement of the oral cavity and pharynx, spontaneous changes of expression muscles, concern about circumstances, voluntary purposeful movement, and coherent verbalization 2 weeks after the operation. As dorsal column stimulation can cause consciousness recovery from the semicomatose state, it should be considered as the treatment choice for the consciousness disturbance.

Whole body cooling in newborn infants with perinatal asphyxial encephalopathy in a low resource setting: a feasibility trial.

OBJECTIVE: To determine the feasibility and safety of whole body cooling in newborn infants with perinatal asphyxial encephalopathy in a low resource setting. DESIGN: Feasibility trial. SETTING: Tertiary care perinatal centre. SUBJECTS: Infants born at > 35 weeks gestation with perinatal asphyxia were included in the study. INTERVENTIONS: Infants were cooled to a rectal temperature of 33 ± 0.5°C for 72 hours using cloth-covered ice-gel packs. Vital parameters were monitored continuously. OUTCOME MEASURES: The primary outcome was the achievement of target temperature within 1 hour of initiation of treatment and maintaining the target temperature for 72 hours. Adverse events and possible complications of hypothermia were the secondary outcomes measured. RESULTS: Twenty infants were included in the study. The mean time taken to achieve target rectal temperature was 52 ± 25 minutes. The mean rectal temperature during cooling was 32.9 ± 0.11ºC. The target temperature could be maintained for 72 hours without difficulty in all babies. Adverse events observed during cooling were thrombocytopenia (25%), sinus bradycardia (25%), deranged bleeding parameters (20%), aposteatonecrosis (15%), hyperglycemia (15%), hypoglycemia (10%), hypoxemia (5%), life-threatening coagulopathy (5%) and death (5%). Shivering was noted in many of the babies, especially in the initial phase of cooling. CONCLUSION: Whole body cooling in term infants with perinatal asphyxia is achievable, safe and inexpensive in a low-resource setting.

Acupuncture as complementary therapy for hypoxic encephalopathy: a case study.

OBJECTIVE: In acute carbon monoxide intoxication, more serious neuronal damage may induce hypoxic encephalopathy with variable degrees of brain damage, ranging from confusion to deep coma. We report herein on a patient who developed hypoxic encephalopathy and acute respiratory failure after acute carbon monoxide intoxication. Acupuncture therapy has been applied along with prescription medication to restore consciousness. CLINICAL PRESENTATION: The patient had a 2-month history of consciousness disturbance and frequent generalised episodic clonic twitching with upward gazing, which was diagnosed as hypoxic encephalopathy. INTERVENTION: Acupuncture therapy has been applied to restore consciousness with routine treatment and medication prescription. The patient was treated 29 times by abdominal acupuncture in conjunction with scalp, body and foot acupuncture according to the 12 meridians' points as an assistant therapy. After 2 months of acupuncture treatment, the patient regained consciousness; the Glasgow Coma Scale (GCS) index increased from 7 to 15, before and after acupuncture therapy. CONCLUSION: This case report suggests that there may be a role for complementary treatment with acupuncture in such cases, and it would be more definitive, meaningful and a welcome addition to our database of knowledge if more case studies about the possibility of acupuncture use in these circumstances were done.

Efficiency and safety of a standardized protocol for intravenous insulin therapy in ICU patients with neurovascular or head injury.

BACKGROUND: To evaluate the safety and efficiency of a protocol for glycemic control in intensive care unit (ICU) patients with neurovascular or head injury. METHODS: Two cohorts of 50 consecutive patients admitted to the ICU with an admission diagnosis of neurovascular or head injury before and after protocol implementation were evaluated. All patients in the interventional cohort received insulin using a standardized intravenous insulin infusion protocol targeting blood glucose levels of 7-9 mmol/l. Efficiency (time to reach and time within target range), safety (hypoglycemia), and nursing compliance (protocol violations) were evaluated. RESULTS: The median time to reach the target blood glucose range was shorter in the interventional cohort than the conventional cohort (5.0 h [0.5-20.5 h] vs. 12.9 h [1.3-90.3 h]; P < 0.001). More time was spent within target range in the interventional cohort than in the conventional cohort (36.4 +/- 16.3% vs. 27.1 +/- 19.0%; P < 0.001). The median prevalence of mild (<4.9 mmol/l) hypoglycemia (0 [0-1.11]% vs. 0.58 [0-2.79]%; P < 0.001) and moderate (<3.9) hypoglycemia (0[0-0.55]% vs. 0 [1-1.25]%; p < 0.001) was significantly lower in the interventional cohort. CONCLUSIONS: The intravenous insulin infusion protocol improved the safety and efficiency of glycemic control for ICU patients with neurovascular or head injury.

Hyperbaric oxygen in neurosurgery.

BACKGROUND: The therapeutic use of pure oxygen, even under hyperbaric conditions, has been well established for about 50 years, whereas the discovery of oxygen occurred 250 years earlier. Many neurosurgical patients suffer from brain tissue damage, due to reduced blood flow, obstructive vessel disease, or as a result of traumatic brain injury. METHODS AND RESULTS: The application of pure oxygen in these patients is the only method of increasing the O(2) concentration in tissue with impaired blood supply and can minimize secondary impairment of brain tissue. DISCUSSION: In this brief historical overview we focus on the development and evidence of hyperbaric oxygenation in this specific field of insufficient oxygen supply to the central neural tissue. CONCLUSION: With the use of modern biological methods and new study designs, HBO has a place in evidence-based treatment of patients with neural tissue damage.