Decreased Blood Oxygen Research Articles

Evaluation of brain function during different types of breathing using FDG-PET compared with using BOLD-fMRI

Mouth breathing can occur due to obstructive, habitual, or anatomical factors, and it causes various side effects such as decreased blood oxygen saturation, respiratory diseases, skeletal disorders in the facial area, decreased concentration, and sleep disorders. However, previous studies on these side effects of mouth breathing have mainly focused on structural changes. Because oxygen and glucose are essential for brain metabolism, studies on their changes due to mouth breathing have been required. Therefore, this study was to investigate the activation of brain regions during different types of breathing (nasal and mouth breathing) using fluorodeoxyglucose (FDG) positron emission tomography (PET) and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI). FDG-PET and BOLD-fMRI data were obtained from ten healthy subjects. Image pre-processing and group analysis were conducted using statistical parametric mapping (SPM12). FDG-PET showed that cerebral areas, such as middle frontal, superior and inferior parietal and inferior frontal gyrus, were highly active during nasal breathing and that the cerebellar areas were highly active during mouth breathing. BOLD-fMRI showed that the inferior occipital and the superior frontal gyrus, and the gyrus rectus were highly active during nasal breathing. This study confirmed that mouth breathing interferes with the normal functioning of the cerebrum, such as its metabolism, thereby reducing the activations of the olfactory, autonomic nervous system, as well as the default mode network. These, along with structural changes, may cause deteriorations in brain functions.

Doğuştan Kalp Hastalıklı Çocuklarda Optik Koherens Tomografi ile Koroid Kalınlığının Değerlendirilmesi

Objective: The main reason for complications in congenital heart diseases (CHD) is decreased blood oxygen saturation and polycythemia which are typical for cyanosis. These parameters may promote the damage of the retina because haemodynamic regulation is essential for the structural and functional integrity of the macular subfields. The aim of this study was to evaluate choroidal thickness (CT) measurements in children with CHD using spectral domain optical coherence tomography (OCT). Methods: This prospective study compared 30 CHD and 30 healthy control children. CT was examined with spectralis spectral-domain OCT (Retinascan RS-3000; Nidek). CT was obtained at the subfovea, 500 μm and 1000 μm nasal to the fovea (N500, N1000) and 500 μm and 1000 μm temporal to the fovea (T500, T1000). Only the right eye values were used for statistical comparisons between the groups. The domain cardiac lesions were divided physiologically into two categories: volume overload and cyanotic. Results: Mean age was 11.0±3.5 years in CHD childrens and 10.9±3.6 years in the control group (p=0.971). Children with CHD had no statistically significant CT measurements compared with healthy controls (p>0.05). Conclusion: Although in high haematocrit, low oxygen saturation or the presence of the volume overload in the history of CHD patients, our data suggests that patients with CHD show normal CT. The reason may be medical and surgical treatment of hypoxia, erythrocytosis and volume overload in CHD patients.

Premedication practices for less invasive surfactant administration — results from a nationwide cohort study

Background and aims There are no established premedication schemes for less invasive surfactant administration (LISA) in neonatal RDS. The aim was to describe "real-world" practices and to assess the safety of premedication and its impact on the technical ease of the LISA procedure. Methods Data from the prospective LISA cohort study conducted in 31 tertiary neonatal units were evaluated for premedication practices. Infants who received analgesics and/or sedatives before LISA and those receiving non-pharmacological sedation with sublingual 30% glucose were compared versus nonpremedicated neonates, acting as a reference. Safety of premedication was assessed with the rate of adverse events during LISA, changes in oxygenation status, the need for rescue intubation, and mechanical ventilation in the first 24 h of life. Ease of conducting LISA was an efficacy endpoint. Results Of 500 enrolled newborns, 102 (20.4%) received premedication for LISA; 88 infants were given analgesics/sedatives and 14 sublingual glucose. Pharmacological sedation was most often performed with ketamine (51/88; 57.9%), midazolam (16/88; 18.2%) and propofol (8/88; 1.6%). Compared to non-premedication, the use of analgesics/sedatives was associated with a significant increase in the rate of apnea (9.1 vs 2.6%; p = 0.009) and a significantly higher decrease in SpO2/FiO2 (−55 ± 62 vs −32 ± 50; p < 0.001). However, the rates of rescue intubation and the need for early mechanical ventilation were not significantly different. Sedation with glucose did not affect the frequency of adverse events. LISA procedures had a similar level of ease regardless of the premedication used and were rated as easy or very easy in 69% of non-premedicated infants, 65.9% of the analgesics/sedatives group and 78.5% of the glucose group (p = ns). Conclusion Analgesics/sedatives prior to LISA increased the rate of apnea and decreased blood oxygenation but did not lead to tracheal intubation and early mechanical ventilation. Trials addressing the impact on LISA-related stress are necessary to determine the ultimate usefulness of premedication.

New Technology for the Use of Inhaled Nitric Oxide to Protect the Heart and Lungs during Operations with Cardiopulmonary Bypass.

The aim of the study was to evaluate the effectiveness of a new technology for the use of inhaled nitric oxide (NO) for the heart and lung protection during operations with cardiopulmonary bypass (СРВ).Materials and Methods.The study included 90 patients who underwent heart valve surgery and combined procedures under CPB and pharmacological cardioplegia. Three groups were created: group 1 (control, n=30); group 2 (n=30) — NO inhalation (20 ppm) was conducted traditionally, that is, before and after CPB; group 3 (n=30) — NO inhalation was performed using a new technology — during the entire operation, with pulmonary artery perfusion and lung ventilation performed during CPB. Troponin I (cTn I) level, changes in the pulmonary function parameters, and clinical indicators were studied.Results.Statistically significant lower levels of postoperative cTn I were registered in the patients of groups 2 and 3, at the same time, the levels were significantly lower in group 3 compared to group 2. The patients in group 1 (standardized anesthesia protocol) demonstrated an increase in the alveolar-arterial oxygen difference, an increase in intrapulmonary shunting, a decrease in blood oxygenation, and static lung compliance after СРВ. In both cases, NO inhalation retained the values of lung compliance and pulmonary oxygenating function after CPB, and in the patients of group 3, it also significantly reduced intrapulmonary shunting and alveolar-arterial difference after CPB. NO inhalation allowed a statistically significant decrease in the incidence of pulmonary dysfunction, acute respiratory failure, as well as the time of respiratory support in the ICU.Conclusion.The developed technology for the use of inhaled NO in surgery with CPB provides a clinically marked protective effect on the heart and lungs. The effectiveness of the protective action of NO depends on the duration of its administration and is most pronounced when used during the entire operation, including CPB time.

Abstract 1: Male Sprague Dawley Rats Exposed To Perinatal Hypoxia Are More Susceptible To Angiotensin II-induced Hypertension In Adulthood Vs Females

Preterm infants (born prior to 37 weeks (wks) gestation) are susceptible to hypoxia, which predisposes to hypertension in later life. Underdeveloped organs, including the kidney, prevent preterm infants from effectively regulating blood volume and O 2 delivery. Since rat nephrogenesis completes ~ postnatal day (PND) 8, we hypothesized that exposure to hypoxia before nephrogenesis is complete will promote hypertension in adulthood. Male and female Sprague Dawley pups were randomized to Ctrl (room air) or intermittent hypoxia (IH) at PND 1 (n=6/group). IH pups were exposed to ~10% O 2 three times a day, 10 minutes/session, from PND 1-8. O 2 saturation was measured at PND 6. Mean arterial pressure (MAP) was measured via telemetry from ~14 – 16 wks of age. To determine the MAP response to a cardiovascular challenge, osmotic minipumps containing angiotensin (Ang) II (400 ng/kg/min) were implanted at 15 wks of age. IH pups had lower O 2 saturation vs ctrl (P O2 &lt;0.05). Light cycle (LC) and dark cycle (DC) MAP were similar in all groups at baseline. Following treatment, LC-MAP was higher in IH-M vs Ctrl-M, but similar among female groups (P Int . = 0.04). IH animals had higher DC-MAP vs ctrl (P O2 = 0.02). IH decreased blood oxygen, suggesting a global decrease in oxygen delivery to organs, similar to what is seen with hypoxia. Perinatal IH alone did not increase MAP. However, this exposure did increase MAP in response to Ang II. While both males and females exposed to perinatal hypoxia had higher Ang II-induced hypertension vs ctrls in the dark cycle, this effect was preserved only in males in the light cycle. This suggests males are more susceptible to blood pressure effects of perinatal IH.

Effects of dietary Original XPC on selected blood variables in layer pullets challenged with Mycoplasma gallisepticum , ,

Effects of dietary Original XPC (XPC) on 17 selected blood variables in commercial layer pullets challenged with the virulent, low-passage R strain of Mycoplasma gallisepticum (RlowMG) were investigated. Hy-Line W-36 pullets sourced from M. gallisepticum–clean layer breeders were fed a basal diet with XPC (1.25 kg/metric ton) or without from hatch until 12 wk of age (woa). At 8 and 10 woa, half of the birds in each dietary treatment were challenged with RlowMG. Blood samples were taken immediately before the initial RlowMG challenge at 8 woa and again at 12 woa (4 wk after challenge). At 8 woa, blood pH was lower and glucose concentration was higher in the preassigned challenge treatment groups. At 12 woa, the concentration of oxygen dissolved in the blood was significantly lower in the RlowMG-challenged group than the unchallenged group of birds regardless of dietary treatment. The RlowMG challenge significantly increased blood carbon dioxide partial pressure, calcium, sodium, anion gap, osmolality, glucose, and corticosterone levels but significantly decreased blood oxygen partial pressure, oxyhemoglobin concentration, concentration of oxygen dissolved in the blood, chloride, and pH levels. Because blood pH and glucose concentration at 8 woa were examined before challenge, their baseline values were biased with respect to challenge treatment before treatment was applied. However, the lack of a significant main effect due to diet at 8 woa for blood pH and glucose concentration, along with the other 15 blood variables, indicate that the baseline data with respect to dietary treatment were unbiased, allowing for real dietary effects to be accurately assessed. In conclusion, layer pullets challenged with RlowMG undergo a stress response associated with changes in various physiological blood variables, and a decrease in pH and increase in carbon dioxide partial pressure, in association with a lack of change in bicarbonate, indicates that the stress response caused by the RlowMG challenge was associated with respiratory acidosis. Nevertheless, feeding XPC did not influence the effects of challenge treatment on these postchallenge physiological blood values.

Combining the use of Nuss procedure and rib fixation for severe flail chest: a case report

BackgroundSevere flail chest is a life-threatening situation. The Nuss procedure is a new effective treatment for severe flail chest patients who cannot be weaned from prolonged mechanical ventilation in the last few years. However, the procedure is not suitable when there are multiple fractures in both the anterior and lateral chest walls. Here, we reported a rare case of severe flail chest in a patient who suffered multiple fractures in both the anterior and lateral chest walls in a traffic accident.Case presentationA 49-year-old patient suffered severe flail chest by a steering wheel in a traffic accident with multiple fractures in both the anterior and lateral chest walls. In the beginning, the patient was administrated with mechanical ventilation because of acute respiratory distress syndrome (ARDS) for more than 1 week. Then the patient suffered from a severe lung infection and decreased blood oxygen saturation. After a multidiscipline discussion (MDT), three rib fixation plates were first used to rebuild the stability of lateral chest walls, then two Nuss bars were inserted to eliminate paradoxical movement in the anterior chest wall. Finally, the patient recovered smoothly after the combining procedure.ConclusionsSevere flail chest patients with both the anterior and lateral chest walls after trauma are in a life-threatening situation, and require an appropriate procedure to get out of danger in time. Rib fixation is an effective treatment when the fractured sites are few and the fractured area is small. The Nuss procedure is a new effective method for severe flail chest with multiple fractures in an anterior chest wall, which is also a minimally invasive and short time-consuming procedure. However, it does not suitable for the patient with multiple fractures in lateral chest walls. Combining the use of Nuss procedure and rib fixation can solve severe flail chest with multiple ribs and sternum fractures in both the anterior and lateral chest walls, and the outcome of this procedure is satisfying in the present rare case.

The risk of bronchial asthma exacerbations among smokers with asthma-chronic obstructive pulmonary disease overlap after inpatient treatment

To assess the risk of exacerbations of bronchial asthma (BA) in smoking patients with the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) after inpatient treatment. 36 smokers with ACO (main group) and 36 non-smoking patients (control group) with severe or moderate exacerbation of bronchial asthma were examined. Assessment of the severity of exacerbation of BA before treatment, levels of control and risk of exacerbations of BA after treatment was determined according to the Federal clinical guidelines for the diagnosis and treatment of BA (2016). Spirometry, monitoring of blood oxygenation using transcutaneous spectral pulse oximetry and enzyme immunoassay for determination of matrix metalloproteinases 9 were performed. Smoking experience, smoking index and pack/years index were taken into account in patients with ACO. The carboxyhaemoglobin level was analyzed by the carbon monoxide fraction in the exhaled air. For the first time in patients with the ACO, the ability of heavy tobacco smoking and associated decrease in blood oxygenation to potentiate the negative impact of other predictors on the risk of exacerbations of the underlying disease was revealed. In smoking patients with the ACO, for the first time, a direct association of higher levels of matrix metalloproteinases 9 (measured before inpatient treatment) with such a predictor of the risk of further exacerbations of the disease as more frequent detection of symptoms of uncontrolled BA was revealed. In non-smoking patients with BA, a direct relationship between increased sputum secretion and eosinophilia of blood and/or sputum (a predictor of exacerbation of BA) and the relative duration of episodes of decreased blood oxygenation was established. It was found that intensive and prolonged smoking increases the duration and reduces the effectiveness of inpatient treatment of patients with ACO, contributing to the preservation of air traps and low (forced expiratory volume in 1 second 60%) ventilation capacity of the lungs with the persistence of moderately reduced blood oxygenation; the risk of further exacerbations of BA in this phenotype of patients is significantly higher than in non-smoking patients with BA without combination with COPD.

Frustration and Emotional Regulation in Nonsyndromic Craniosynostosis: A Functional Magnetic Resonance Imaging Study.

Nonsyndromic craniosynostosis may manifest with complex behavioral, attentional, and emotional sequelae. The authors characterized higher level brain connectivity in adolescent nonsyndromic craniosynostosis patients in response to emotional frustration. Surgically corrected patients older than 9 years with nonsyndromic craniosynostosis were age/sex/handedness matched to controls. Patients participated in a "go/no-go" task, structured as win/lose/recovery paradigms. BioImage Suite was used to analyze whole-brain intrinsic connectivity between tasks with cluster-corrected group-level t maps. A value of p < 0.05 was significant. Seven unilateral coronal (average age, 12.2 years), six metopic (average age, 11.5 years), and controls were included. Unilateral coronal had worse emotional regulation scores on the Behavior Rating Inventory of Executive Function survey (p = 0.065) and performed poorly on the go/no-go task (p < 0.001). Metopic had four regions of interest, with the majority having decreased activity compared with controls, and few differences between tasks. Unilateral coronal patients had 11 regions of interest; the majority decreased during the win and lose conditions, but all increased during the recovery condition. Metopic patients had decreased blood oxygenation level- dependent signal in the posterior cingulate (p = 0.017) and middle temporal gyrus (p = 0.042). Unilateral coronal had decreased signal in the posterior cingulate (p = 0.023), middle temporal gyrus (p = 0.027), and thalamus (p = 0.033), but increased signal in the cuneus (p = 0.009) and cerebellum (p = 0.009). Right unilateral coronal, but not metopic/controls, had increased right brain activity in the caudate (p = 0.030), thalamus (p = 0.011), temporal lobe (p = 0.012), and cerebellum (p = 0.029). Unilateral coronal patients may have emotional dysregulation in response to frustration, whereas metopic patients may have attenuated emotional reactions. Evidence of right unilateral coronal brain laterality suggests that the area of suture fusion may contribute to the mechanism of dysfunction. Risk, II.

Update: Interim Guidance for Health Care Providers Evaluating and Caring for Patients with Suspected E-cigarette, or Vaping, Product Use Associated Lung Injury - United States, October 2019.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical partners are investigating a multistate outbreak of lung injury associated with the use of electronic cigarette (e-cigarette), or vaping, products. In late August, CDC released recommendations for health care providers regarding e-cigarette, or vaping, product use associated lung injury (EVALI) based on limited data from the first reported cases (1,2). This report summarizes national surveillance data describing clinical features of more recently reported cases and interim recommendations based on these data for U.S. health care providers caring for patients with suspected or known EVALI. It provides interim guidance for 1) initial clinical evaluation; 2) suggested criteria for hospital admission and treatment; 3) patient follow-up; 4) special considerations for groups at high risk; and 5) clinical and public health recommendations. Health care providers evaluating patients suspected to have EVALI should ask about the use of e-cigarette, or vaping, products in a nonjudgmental and thorough manner. Patients suspected to have EVALI should have a chest radiograph (CXR), and hospital admission is recommended for patients who have decreased blood oxygen (O2) saturation (<95%) on room air or who are in respiratory distress. Health care providers should consider empiric use of a combination of antibiotics, antivirals, or steroids based upon clinical context. Evidence-based tobacco product cessation strategies, including behavioral counseling, are recommended to help patients discontinue use of e-cigarette, or vaping, products. To reduce the risk of recurrence, patients who have been treated for EVALI should not use e-cigarette, or vaping, products. CDC recommends that persons should not use e-cigarette, or vaping, products that contain tetrahydrocannabinol (THC). At present, CDC recommends persons consider refraining from using e-cigarette, or vaping, products that contain nicotine. Irrespective of the ongoing investigation, e-cigarette, or vaping, products should never be used by youths, young adults, or women who are pregnant. Persons who do not currently use tobacco products should not start using e-cigarette, or vaping, products.

Prevalence of Obstructive Sleep Apnea Syndrome in Psoriasis Patients

Aim: Psoriasis is a frequently seen chronic systemic inflammatory disease accompanied by several comorbid conditions that affects 2-3% of the general population. One of the comorbidities rarely accompanying psoriasis is obstructive sleep apnea syndrome (OSAS). OSAS is a disease characterized by recurrent complete (apnea) or partial (hypopnea) upper airway obstruction episodes and frequently by decreased blood oxygen saturation. The purpose of this study was to evaluate the risk factors for OSAS by investigating OSAS symptoms in psoriasis patients.Material and Methods: Eighty-two patients aged over 16, diagnosed with psoriasis, and under follow-up by the Duzce University Medical of Faculty, Dermatology and Venereal Diseases Polyclinic, Turkey, were included in the study. Patients’ OSAS symptoms were investigated. The Epworth Sleepiness Scale was used to assess excessive daytime somnolence.Results: Of the patients 51.2% (n=42) were male and 48.8% (n=40) female. Patients’ mean age was 47.09±14.10 years. Patients’ mean time of psoriasis diagnosis was 16.97±10.55 years, and mean Psoriatic Area Severity Index (PASI) score was 11.25±6.32. Severe disease was present in 54.9% of patients (n=45) based on PASI classification. Prevalence of 56.1% for snoring, 25.6% for excessive daytime sleepiness, and 15.9% for witnessed apnea were determined in these patients. Forty-seven (57.3%) cases had at least one major symptom. The most common minor symptoms were inability to sleep with 25.6% (n=21) and insufficient disrupted sleep with 22.0% (n=18).Conclusion: Prevalence of OSAS symptoms in psoriasis patients were found high. Psoriasis patients with OSAS symptoms must be referred to relevant specialists for polysomnographic evaluation.

Chronic Alcohol Significantly Affects Pulmonary Function Both at Baseline and in Response to Endotoxemia

Acute respiratory distress syndrome (ARDS) is an inflammatory disease characterized by significant pulmonary edema and pathologic alveolar flooding due to disrupted fluid homeostasis and increased alveolar permeability. ARDS accounts for 10% of global ICU admissions annually and carries a significant mortality risk. Chronic alcohol abuse exacerbates acute lung injury and is an independent risk factor to develop ARDS. Alveolar epithelial permeability is regulated by claudin‐family proteins that are incorporated into structures known as tight junctions. We have found that chronic alcohol negatively impacts alveolar barrier function in vitro by changing claudin expression and integration into tight junctions. Defining the molecular mechanisms responsible for the increased incidence of ARDS seen with chronic alcohol abuse is critical to understand the pathology of ARDS. In this study we used an Evans Blue permeability assay to assess changes in alveolar and vasculature permeability due to alcohol in combination with endotoxin as a ‘second‐hit’ to mimic the effects of pneumonia and sepsis on the lung. We also assessed the effects of alcohol and endotoxemia injury on pulmonary barrier function comparing intraperitoneal (IP) and intratracheal (IT) administration. Consistent with previous reports, we found that in alcohol‐fed mice, the alveolar barrier was impaired by both IP and IT endotoxin, allowing Evans Blue to permeate into the airspaces. However, protein content of airspaces was significantly higher in lungs treated with IT endotoxin as compared with IP which we attribute to a heightened inflammatory response in response to endotoxin. We also assessed whether the alcoholic lung is more susceptible to pulmonary edema due to increased fluid pressure from the interstitium (pulmonary wedge pressure). Alcohol‐fed mice showed increased susceptibility to alveolar leak when subjected to increased fluid pressure as compared with water‐fed controls. To test if alcohol‐induced increases in permeability affect pulmonary function and normal gas exchange, arterial oxygen saturation was measured and we found that there was a statistically significant decrease in blood oxygenation in alcohol‐fed mice at baseline as compared with water‐fed controls (97.3 ± 0.3 (n=4) vs 99.3 ± 1 (n=6)) predisposing them to hypoxia. Additionally, we have previously shown that primary alveolar cells cultured from alcohol‐fed rats continue to demonstrate defects in barrier function even after differentiation. We then performed an alcohol withdrawal experiment in mice and found a persistent effect on permeability even after 6 weeks without dietary alcohol. These results suggest alcohol has long lasting effects on the cellular biology and barrier function of alveolar epithelial cells. Current studies are focusing on targeting the tight junction protein Claudin‐5 as a potential mediator of alcoholic lung syndrome, using a specific antagonist peptide to rescue alcohol‐induced barrier dysfunction in vivo.Support or Funding InformationThis work was supported by R01‐AA025854, R01‐HL137112 (M.K.) and K12‐GM000680 (P.S.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The study about the change of the blood oxygen saturation and pulse rate of the nursing staff under abrupt highland advancing.

Objective To evaluate the changes in blood oxygen saturation and pulse rate of the nurses under abrupt highland advancing and provide the fundamentals for those nurses under abrupt highland advancing to Tibet. Methods We selected 12 nursing staffs abruptly advanced to Lhasa at an altitude of 3 650 meters for Abrupt Advancing Group then chose 12 nursing staffs over there for Highland Group from November 2017 to December 2017. To assess whether there is a difference about the change of blood oxygen saturation and pulse rate between these two groups, we measured them in 24 nurses and 360 shifts before work and at 0.5, 1.0, 3.0, 6.0 h after work. Then, we compared the changes in blood oxygen saturation and pulse rate between different ages, sexes, shifts. Results No significant difference in blood oxygen saturation was observed between the two groups before starting work (P > 0.05). Blood oxygen saturation of Abrupt Advancing Group (0.5, 1.0, 3.0, 6.0 h) after work was respectively 0.91±0.01, 0.91±0.02, 0.91±0.02, 0.91±0.01. Meanwhile, the parameters of Highland Group was separately 0.94±0.02, 0.93±0.01, 0.94±0.01, 0.94±0.01. There was a significant difference between the two groups (t=5.153-8.151, P 0.05). A positive difference between the sexes could be found about the changes in the blood oxygen saturation of Abruptly Advancing Group at 0.5, 1.0, 3.0 and 6.0 h after work. What′s more, there was a significant difference in pulse rates before and after work (t=3.283-6.719, P < 0.05 or 0.01). Conclusions The nursing staff in the Abruptly Advancing Group shows decreased blood oxygen saturation and increased pulse rate compared to those in the Highland Group during working period. In addition, the changes show more significant in those working at night, but they adapted gradually. Gender and working time have a significant effect on the change in blood oxygen saturation and increased pulse rate of the nursing staff. Key words: Nurses; Abruptly highland advancing; Oxygen saturation

Functional Magnetic Resonance Imaging of Inhibitory Control Reveals Decreased Blood Oxygen Level Dependent Effect in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

Background and Purpose- Small-vessel damage in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is associated with impaired vascular constriction and dilation. We used a functional magnetic resonance imaging task with an event-related design of stimulus to explore the anticipated abnormally decreased blood oxygen level dependent effect in CADASIL. Methods- Twenty-one CADASIL patients and 16 healthy controls performed a Go/No-go task exploring reactive and proactive phases of inhibition control in a 3-T magnet. Results- Error number and reaction times were not different between patients and controls. Analysis of the reactive inhibition (No-go/baseline contrast) did not show clusters of lower or higher blood oxygen level dependent effect in patients or controls. Analysis of the proactive inhibition (alertness contrast) in CADASIL patients revealed a lower blood oxygen level dependent effect in the alerting network (anterior cingulate cortex and insula, thalamus), lower brain stem and left cerebellar hemisphere (crus I) that is involved in executive functions. Conclusions- In CADASIL patients, an event-related Go/No-go task reveals a lower blood oxygen level dependent effect in the alerting network and areas involved in executive functions possibly reflecting the altered hemodynamic response secondary to small-vessel changes. Our observation extends the role of MR in demonstrating one of the fundamental pathophysiological changes of CADASIL.

Inhibitory Neuron Activity Contributions to Hemodynamic Responses and Metabolic Load Examined Using an Inhibitory Optogenetic Mouse Model.

Hemodynamic signals are routinely used to noninvasively assess brain function in humans and animals. This work examined the contribution of inhibitory neuron activity on hemodynamic responses captured by changes in blood flow, volume and oxygenation in the cortex of lightly anesthetized mice. Because cortical activity is not commonly initiated by inhibitory neurons, experiments were conducted to examine the neuronal activity properties elicited by photo-stimulation. We observed comparable increases in neuronal activity evoked by forelimb and photo-stimulation; however, significantly larger increases in blood flow and volume were produced by photo-stimulation of inhibitory neurons compared with forelimb stimulation. Following blockade of glutamate and GABA-A receptors to reduce postsynaptic activity contributions, neuronal activity was reliably modulated and hemodynamic changes persisted, though slightly reduced. More importantly, photo-stimulation-evoked changes in blood flow and volume were suppressed by 75–80% with the administration of a nitric oxide synthase inhibitor, suggesting that inhibitory neurons regulate blood flow mostly via nitric oxide. Lastly, forelimb and photo-stimulation of excitatory neurons produced local decreases in blood oxygenation, while large increases were generated by photo-stimulation of inhibitory neurons. Estimates of oxygen metabolism suggest that inhibitory neuron activity has a small impact on tissue metabolic load, indicating a mismatch between the metabolic demand and blood flow regulation properties of inhibitory and excitatory neurons.

Unilateral nasal obstruction induces morphological changes of the mandibular condyle in growing rats

PurposeChronic nasal obstruction is known to decrease blood oxygen saturation. Mouth breathing in association with chronic nasal obstruction leads to the collapse of the buccinator mechanism and to a clockwise rotation of the mandible, which causes mandibular retrusion. This study aimed to investigate the influences of nasal obstruction on the morphological and histological changes of the mandible in growing rats. Materials and methodsThirty 8-day-old male Wistar rats were randomly divided into the control and experimental groups. The experimental group underwent unilateral nasal obstruction by cauterization of the external nostrils at 8days of age. Pulse oxygen saturation (SpO2) was monitored every week. Rats were sacrificed at 9 weeks of age. The mandibular changes were analyzed via lateral cephalometric radiographs and micro-CT scans. We utilized toluidine blue and tartrate-resistant acid phosphatase (TRAP) staining for histological analysis. Immunohistochemical staining of hypoxia induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), osteoprotegerin (OPG) receptor activator of nuclear factor kappa-B ligand (RANKL) were also performed to reveal the mechanism of the morphological changes. ResultsSpO2 was significantly lower in the experimental than in the control group. In the experimental group, length, bone mineral density and cartilage layer thickness of mandibular condyle were decreased. The number of TRAP-positive cells in the condyle, HIF-1α-positive cells, VEGF-positive cells and RANKL-positive cells in the condylar cartilage was significantly increased. In contrast, a reduced expression of OPG protein was observed in the experimental group. ConclusionsOur findings suggest that unilateral nasal obstruction in the growth period affects mandibular morphology.

Recognizing visual speech: Reduced responses in visual-movement regions, but not other speech regions in autism.

Speech information inherent in face movements is important for understanding what is said in face-to-face communication. Individuals with autism spectrum disorders (ASD) have difficulties in extracting speech information from face movements, a process called visual-speech recognition. Currently, it is unknown what dysfunctional brain regions or networks underlie the visual-speech recognition deficit in ASD.We conducted a functional magnetic resonance imaging (fMRI) study with concurrent eye tracking to investigate visual-speech recognition in adults diagnosed with high-functioning autism and pairwise matched typically developed controls.Compared to the control group (n = 17), the ASD group (n = 17) showed decreased Blood Oxygenation Level Dependent (BOLD) response during visual-speech recognition in the right visual area 5 (V5/MT) and left temporal visual speech area (TVSA) – brain regions implicated in visual-movement perception. The right V5/MT showed positive correlation with visual-speech task performance in the ASD group, but not in the control group. Psychophysiological interaction analysis (PPI) revealed that functional connectivity between the left TVSA and the bilateral V5/MT and between the right V5/MT and the left IFG was lower in the ASD than in the control group. In contrast, responses in other speech-motor regions and their connectivity were on the neurotypical level.Reduced responses and network connectivity of the visual-movement regions in conjunction with intact speech-related mechanisms indicate that perceptual mechanisms might be at the core of the visual-speech recognition deficit in ASD. Communication deficits in ASD might at least partly stem from atypical sensory processing and not higher-order cognitive processing of socially relevant information.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex.

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants.

Chronic lung injury and impaired pulmonary function in a mouse model of acid ceramidase deficiency.

Farber disease (FD) is a debilitating lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical phenotypes. Severe cases of FD are frequently associated with neurological involvement, failure to thrive, and respiratory complications. Mice homozygous ( Asah1P361R/P361R) for an orthologous patient mutation in Asah1 recapitulate human FD. In this study, we show significant impairment in lung function, including low compliance and increased airway resistance in a mouse model of ACDase deficiency. Impaired lung mechanics in Farber mice resulted in decreased blood oxygenation and increased red blood cell production. Inflammatory cells were recruited to both perivascular and peribronchial areas of the lung. We observed large vacuolated foamy histiocytes that were full of storage material. An increase in vascular permeability led to protein leakage, edema, and impacted surfactant homeostasis in the lungs of Asah1P361R/P361R mice. Bronchial alveolar lavage fluid (BALF) extraction and analysis revealed accumulation of a highly turbid lipoprotein-like substance that was composed in part of surfactants, phospholipids, and ceramides. The phospholipid composition of BALF from Asah1P361R/P361R mice was severely altered, with an increase in both phosphatidylethanolamine (PE) and sphingomyelin (SM). Ceramides were also found at significantly higher levels in both BALF and lung tissue from Asah1P361R/P361R mice when compared with levels from wild-type animals. We demonstrate that a deficiency in ACDase leads to sphingolipid and phospholipid imbalance, chronic lung injury caused by significant inflammation, and increased vascular permeability, leading to impaired lung function.

Intravenous Heroin Induces Rapid Brain Hypoxia and Hyperglycemia that Precede Brain Metabolic Response.

Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100-200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity.