Search

Traumatic brain injury (TBI) is a major public health burden, causing death and disability worldwide. Intracranial hypertension and brain hypoxia are the main mechanisms of secondary brain injury. As such, management strategies guided by intracranial pressure (ICP) and brain oxygen (PbtO2) monitoring could improve the prognosis of these patients. Our objective was to summarize the current evidence regarding the impact of PbtO2-guided therapy on the outcome of patients with TBI. We performed a systematic search of PubMed, Scopus, and the Cochrane library databases, following the protocol registered in PROSPERO. Only studies comparing PbtO2/ICP–guided therapy with ICP-guided therapy were selected. Primary outcome was neurological outcome at 3 and 6 months assessed by using the Glasgow Outcome Scale; secondary outcomes included hospital and long-term mortality, burden of intracranial hypertension, and brain tissue hypoxia. Out of 6254 retrieved studies, 15 studies (n = 37,245 patients, of who 2184 received PbtO2-guided therapy) were included in the final analysis. When compared with ICP-guided therapy, the use of combined PbO2/ICP–guided therapy was associated with a higher probability of favorable neurological outcome (odds ratio 2.21 [95% confidence interval 1.72–2.84]) and of hospital survival (odds ratio 1.15 [95% confidence interval 1.04–1.28]). The heterogeneity (I2) of the studies in each analysis was below 40%. However, the quality of evidence was overall low to moderate. In this meta-analysis, PbtO2-guided therapy was associated with reduced mortality and more favorable neurological outcome in patients with TBI. The low-quality evidence underlines the need for the results from ongoing phase III randomized trials. [ABSTRACT FROM AUTHOR]

Background: Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor paralysis, tremor,and cognitive impairment. Risk factors such as brain hypoxia caused by aging and abnormal expression of HIF-1α areconsidered to be key to the development of PD, including α-synuclein accumulation and ferroptosis. However, therelationship between HIF-1α signaling and ferroptosis in PD has not been elucidated. The stable expression of HIF-1αinhibits the pathological development of PD. Aging aggravates PD pathology by promoting α-synuclein accumulationand oxidative stress.The literature on lipid peroxidation, oxidative stress, iron metabolism and other key factors in Parkinson'sdisease in recent years was reviewed through a variety of literature search channels, such as PubMed and Elsevier.HIF-1α mediated ferroptosis through oxidative stress and GPX4-GSH system. HIF-1α mediates ferroptosisthrough Keap1-Nrf2-ARE, Grx3 and Grx4. HIF-1α mediates ferroptosis through iron metabolism.This article reviews the oxygen-dependent regulatory mechanism of HIF-1α and its role in cerebralhypoxia homeostasis. Studies in the past decade have shown that Hif-1α mediated ferroptosis is important in PD.HIF-1α has a dual role, depending on the degree of cellular hypoxia and the environment. The equilibrium complexityneeds to be explained, and the role of ferroptosis needs to be investigated. The literature shows that the stabilizationof HIF-1α with PHD inhibitors and the combination of antioxidants and iron chelators are potential therapeuticdirections. In the future, the optimal use time and dose of inhibitors should be studied to improve the efficacy.Methods: Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor paralysis, tremor,and cognitive impairment. Risk factors such as brain hypoxia caused by aging and abnormal expression of HIF-1α areconsidered to be key to the development of PD, including α-synuclein accumulation and ferroptosis. However, therelationship between HIF-1α signaling and ferroptosis in PD has not been elucidated. The stable expression of HIF-1αinhibits the pathological development of PD. Aging aggravates PD pathology by promoting α-synuclein accumulationand oxidative stress.The literature on lipid peroxidation, oxidative stress, iron metabolism and other key factors in Parkinson'sdisease in recent years was reviewed through a variety of literature search channels, such as PubMed and Elsevier.HIF-1α mediated ferroptosis through oxidative stress and GPX4-GSH system. HIF-1α mediates ferroptosisthrough Keap1-Nrf2-ARE, Grx3 and Grx4. HIF-1α mediates ferroptosis through iron metabolism.This article reviews the oxygen-dependent regulatory mechanism of HIF-1α and its role in cerebralhypoxia homeostasis. Studies in the past decade have shown that Hif-1α mediated ferroptosis is important in PD.HIF-1α has a dual role, depending on the degree of cellular hypoxia and the environment. The equilibrium complexityneeds to be explained, and the role of ferroptosis needs to be investigated. The literature shows that the stabilizationof HIF-1α with PHD inhibitors and the combination of antioxidants and iron chelators are potential therapeuticdirections. In the future, the optimal use time and dose of inhibitors should be studied to improve the efficacy.Results: Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor paralysis, tremor,and cognitive impairment. Risk factors such as brain hypoxia caused by aging and abnormal expression of HIF-1α areconsidered to be key to the development of PD, including α-synuclein accumulation and ferroptosis. However, therelationship between HIF-1α signaling and ferroptosis in PD has not been elucidated. The stable expression of HIF-1αinhibits the pathological development of PD. Aging aggravates PD pathology by promoting α-synuclein accumulationand oxidative stress.The literature on lipid peroxidation, oxidative stress, iron metabolism and other key factors in Parkinson'sdisease in recent years was reviewed through a variety of literature search channels, such as PubMed and Elsevier.HIF-1α mediated ferroptosis through oxidative stress and GPX4-GSH system. HIF-1α mediates ferroptosisthrough Keap1-Nrf2-ARE, Grx3 and Grx4. HIF-1α mediates ferroptosis through iron metabolism.This article reviews the oxygen-dependent regulatory mechanism of HIF-1α and its role in cerebralhypoxia homeostasis. Studies in the past decade have shown that Hif-1α mediated ferroptosis is important in PD.HIF-1α has a dual role, depending on the degree of cellular hypoxia and the environment. The equilibrium complexityneeds to be explained, and the role of ferroptosis needs to be investigated. The literature shows that the stabilizationof HIF-1α with PHD inhibitors and the combination of antioxidants and iron chelators are potential therapeuticdirections. In the future, the optimal use time and dose of inhibitors should be studied to improve the efficacy.Conclusion: Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor paralysis, tremor,and cognitive impairment. Risk factors such as brain hypoxia caused by aging and abnormal expression of HIF-1α areconsidered to be key to the development of PD, including α-synuclein accumulation and ferroptosis. However, therelationship between HIF-1α signaling and ferroptosis in PD has not been elucidated. The stable expression of HIF-1αinhibits the pathological development of PD. Aging aggravates PD pathology by promoting α-synuclein accumulationand oxidative stress.The literature on lipid peroxidation, oxidative stress, iron metabolism and other key factors in Parkinson'sdisease in recent years was reviewed through a variety of literature search channels, such as PubMed and Elsevier.HIF-1α mediated ferroptosis through oxidative stress and GPX4-GSH system. HIF-1α mediates ferroptosisthrough Keap1-Nrf2-ARE, Grx3 and Grx4. HIF-1α mediates ferroptosis through iron metabolism.This article reviews the oxygen-dependent regulatory mechanism of HIF-1α and its role in cerebralhypoxia homeostasis. Studies in the past decade have shown that Hif-1α mediated ferroptosis is important in PD.HIF-1α has a dual role, depending on the degree of cellular hypoxia and the environment. The equilibrium complexityneeds to be explained, and the role of ferroptosis needs to be investigated. The literature shows that the stabilizationof HIF-1α with PHD inhibitors and the combination of antioxidants and iron chelators are potential therapeuticdirections. In the future, the optimal use time and dose of inhibitors should be studied to improve the efficacy. [ABSTRACT FROM AUTHOR]

Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease. To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS. This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia. PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe2+ efflux and regulating mitochondrial Fe2+ transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer). This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS. [Display omitted] [ABSTRACT FROM AUTHOR]

Minimally invasive cardiac surgery (MICS) for mitral valve repair often uses cardiopulmonary bypass (CPB) through peripheral femoro-femoral cannulation. A rare complication of differential hypoxemia can cause upper body hypoxia.A 38-year-old man with Barlow Syndrome underwent MICS mitral valve repair with peripheral CPB. During the procedure, his right upper limb SpO2 dropped to 65% due to dislodgement of the venous cannula from the superior vena cava (SVC), causing inadequate right heart venous drainage, leading to differential hypoxemia. Repositioning the venous cannula to the SVC restored SpO2 to 100%, allowing the surgery to proceed without complications.Differential hypoxemia happens when deoxygenated blood from the left ventricle mixes with oxygenated CPB blood. A literature review found only one previous case of this complication on peripheral CPB for MICS. Unlike our case, Kanda et al. monitored cerebral hypoxia, underscoring the importance of cerebral oxygenation monitoring in future MICS procedures due to higher stroke risk compared to conventional sternotomy.We recommend cerebral oxygenation monitoring in future MICS to prevent neurological complications, and highlight the need for effective team communication in the cardiac operating theatre. [ABSTRACT FROM AUTHOR]

Endotracheal intubation (ETI) is a common intervention performed in a pediatric emergency. The pediatric laryngeal anatomy creates a challenge and requires an expertise for this procedure. Tracheal injury is a rare but serious complication that can occur during ETI. The stylet, if used improperly, can lead to this life-threatening complication. Here, we present a case of tracheal injury in an infant that happened during ETI with stylet use. [ABSTRACT FROM AUTHOR]

Introduction: Neurodevelopmental impairment is a growing concern for preterm infants who received surgical ligation of patent ductus arteriosus (PDA). We aimed to explore the cerebral hemodynamics during the critical period of PDA ligation. Methods: Very-low-birth-weight (VLBW) preterm infants who underwent PDA ligation were prospectively enrolled. Patients were monitored preoperatively and until 72 h post-ligation. Middle cerebral artery (MCA) flow, regional cerebral oxygen saturation (rcSO2), and cardiac output were measured through Doppler ultrasound, near-infrared spectroscopy, and electrical cardiometry, respectively. Using rcSO2 <55% indicating cerebral hypoxia, the duration (% of time) and burden (cumulative negative quantity of rsSO2 <55% × the period [minutes]) were estimated. An abnormal MCA was defined as an MCA flow of <10th percentile of flow velocity or >90th percentile of pulsatility or resistance index. Poor outcomes were defined as in-hospital death or neurologic disorders, either neuroimaging or functional abnormalities, upon discharge. Results: Thirty-two VLBW infants were examined, and 15 (46.9%) had poor outcomes. Infants with poor outcomes had significantly longer duration of cerebral hypoxia (5.4 [2.2–32.3] vs. 1.8 [0.4–5.6] %, p = 0.033) and worse hypoxic burden (2,118 [684–13,549] vs. 622 [88–1,669] %minutes, p = 0.027). In a linear mixed model, rcSO2 was positively correlated with arterial saturation (β 0.860, 95% CI: 0.649–1.070) and negatively correlated with abnormal MCA flow (β −5.287, 95% CI: −8.238 to −2.335). Conclusion: Longer duration of cerebral hypoxia and worse hypoxic burden post-ligation was associated with an increased risk of in-hospital mortality or neurologic disorders upon discharge in VLBW preterm infants. [ABSTRACT FROM AUTHOR]

Currently, there is a new surge of interest in the problem of hypoxia, almost lost in recent decades. Due to the fact that the circle of competent specialists in this field has significantly narrowed, it is necessary to carry out an intensive exchange of knowledge. In order to inform a wide range of interested researchers and doctors, this review summarizes the current understanding of hypoxia, its pathogenic and adaptogenic consequences, as well as key physiological and molecular mechanisms that implement the response to hypoxia at various levels—from cellular to organismic. The review presents a modern classification of forms of hypoxia, the understanding of which is necessary for the formation of a scientifically based approach to experimental modeling of hypoxic states. An analysis of the literature covering the history and current level of hypoxia modeling in mammals and human experiments, including methods for creating moderate hypoxia used to increase the resistance of the nervous system to severe forms of hypoxia and other extreme factors, is carried out. Special attention is paid to the discussion of the features and limitations of various approaches to the creation of hypoxia, as well as the disclosure of the potential for the practical application of moderate hypoxic effects in medicine. [ABSTRACT FROM AUTHOR]

Behavioral changes in newborn 3-day-old rats (n=44) with modeled hypoxic-ischemic brain injury (HIBI) were observed, and the expression of CDK8 in brain tissues was detected to clarify the significance of CDK8. In 30 min, 3 h, and 3 days after HIBI, the left (ischemic) hemisphere was taken for examination. In 3 days after HIBI, the rat pups were examined in the behavioral tests. In rat pups with HIBI, changes of CDK8 expression were detected by Western blotting and real-time PCR and changes in the righting reflex and forelimb grip strength test (p<0.05) were revealed in comparison with sham-operated animals. The expression of CDK8 increased 30 min after HIBI and decreased in 3 h and 3 days. Hypoxia and ischemia of the left brain may affect locomotion, but not sensation. Since CDK8 is involved in the immune response after cerebral hypoxia and ischemia, this kinase can be used as an early diagnostic index. [ABSTRACT FROM AUTHOR]

Since 2020, the COVID-19 pandemic, triggered by SARS-CoV-2, represents the major global issue affecting the lifestyle of people around the world. Wuhan, China was the first city to detect the SARS-CoV-2 virus, but the virus soon spread around the world, forcing the World Health Organization to declare a global epidemic on March 11, 2020 (1). Previous pathological conditions or comorbidities such as old age are one of the main causes of premature death and increased morbidity and mortality due to COVID-19 (4). Inactivity due to hospitalization and bed rest and reduced physical activity due to constant quarantine and social distancing can reduce the ability of organ systems to resist viral infection and the risk of damage to the immune, respiratory, and Increase cardiovascular systems, musculoskeletal and nervous system (4). On the other hand, the health benefits of physical activity, from cardiovascular health to mental health, have been well established (5). Decreased physical activity and increased sedentary behaviors were reported during quarantine in several populations, including children and patients with a variety of medical conditions (6). In general, COVID)19 lifestyle changes have led to a decrease in physical activity and consequently more inactivity in different parts of the community, which can pose a risk to general or mental health, especially for certain populations. In this study, we have tried to review the neurological and psychological effects of COVID-19 and the resulting lifestyle changes, and specifically the role of exercise in relation to these effects. Central nervous system (CNS) and peripheral nervous system (PNS) manifestations can occur during and after COVID-19, but the underlying mechanisms, symptomatology, and frequency of these complications are not well understood (7). Limited postmortem studies have shown signs of hypoxic brain damage and inflammatory neurological changes in the brainstem, while neuropathological data from the PNS are almost non-existent. Due to the cause, direct invasion of acute respiratory syndrome of COVID-19 virus to nerve tissue has been suggested in several cases, but autoimmune damage and neurological complications related to intensive care management can also be effective. The contribution of these mechanisms to the overall burden of CNS and PNS complications of COVID-19 is unknown (7). Follow-ups in Germany and the United Kingdom have shown that neuropsychological symptoms after COVID-19 in 20 to 70% of patients, even in young adults, last for months after the onset of respiratory symptoms, suggesting brain involvement persists (9). COVID-19, which enters through angiotensin)converting enzyme receptors, can damage endothelial cells, leading to inflammation, thrombosis, and brain damage. In addition, systemic inflammation leads to a decrease in monoamines and neurotrophic factors and activation of microglia, which leads to an increase in glutamate and N-methyl-d-aspartate-3 and excitatory toxicity, and these factors cause the onset or exacerbation of existing neuropsychiatric symptoms. They are already (9). However, the extent of damage caused by the COVID-19 pandemic strain is still speculated; it has recently been suggested that irregular neuro-endocrine-immune interactions may be behind psychiatric manifestations observed in quarantined individuals (12, 13). Persistent and increased stressful events can direct immune, endocrine, and nervous system responses primarily through hypothalamic-pituitary-adrenal (HPA) mediated dysfunction (12), and changes in the levels of systemic inflammatory mediators or the brain predispose individuals to pathological psychological conditions. It acts like anxiety and depression. In addition, stress can be a potential trigger for neuroinflammation, a term used to indicate an imbalance or intensification of immune signals in the brain that can lead to several disorders such as aggression, psychosis, depression, and anxiety disorders (12). Covid 19 has also been shown to alter nerve growth factors that may affect the neuropsychological effects of Covid-19 (16,17). The current situation of the epidemic as a stressful situation has led to a decrease in physical activity in the general population. Considering that exercise training has been shown to be useful in a number of pathologies with which post-COVID-19 syndrome bears similarities in terms of symptoms and possible pathogenic mechanisms; therefore, it is necessary to consider the potential optimal effect that this has on the improvement or prevention of COVID-19 neuropsychiatric complications. Despite the benefits of exercise, there are limitations to sports activities for different people, which can endanger the neurological and mental health of different people, especially people with underlying diseases or people with special conditions such as patients, children and the elderly. A review of a study that specifically looked at the effect of exercise training on nerve function in patients with COVID-19 were not found; However, based on trials, general recommendations for exercise training in patients have been identified that may be beneficial to the neurocognitive effects of COVID-19 in both healthy individuals and those with COVID-19 syndrome. There is ample evidence that appropriate, supervised exercise may be an effective multisystem therapy to reduce the neuropsychological effects of COVID-19 syndrome, which is commensurate with the variety of cases and symptoms. Further studies on the effects of exercise-based therapies on post-COVID-19 syndrome are needed to provide practical insights into what type of exercise training should preferably be prescribed, with an emphasis on weight management and adherence strategies. In addition, the effect of post-COVID-19 syndrome on neuropsychological complications of certain demographic groups such as children, adolescents or the elderly remains unknown; Even exercise training and rehabilitation programs for neuropsychiatric complications in these individuals are not known. Overall, a multidisciplinary and integrated approach, part of which is related to sports science, is essential to improve individuals' clinical conditions; nevertheless, neurological and psychological aspects must be integrated into the assessment, as well as the social impact that this pathology entails. Due to the limitations of studies, new proposals for long-term research into the disease in an effort to restore full function and return to previous life are recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: The extent of tumour oxygenation is crucial for glioblastoma progression and the effectiveness of radio- and chemotherapy. Patient-derived in vitro cell cultures are the mainstay of molecular biology research, the discovery of new therapeutic targets, and drug testing. Therefore, mirroring as many aspects of in vivo settings as possible, including oxygen concentration, is desired. Here we analyse the effect of oxygen tension on the transcriptome of numerous patient-derived GBM cells and demonstrate that cells cultured in lowered oxygen tension express more genes indicative of higher levels of hypoxia, metabolic adaptation, stemness and tumour progression than cells growing in standard, atmospheric oxygen concentration. The same transcriptomic pattern was also found in primary GBM samples. Its specificity for GBMs was confirmed using the public TCGA dataset. Our data strongly argue for the benefit of lower oxygen tension during culturing of patient-derived GBM cells to preserve oxygen-sensitive pathways in GBM. The proposed approach better mimics certain aspects of GBM pathophysiology than traditional cultures and may advance GBM research in finding a cure. Despite numerous efforts aiming to characterise glioblastoma pathology (GBM) and discover new therapeutic strategies, GBM remains one of the most challenging tumours to treat. Here we propose the optimisation of in vitro culturing of GBM patient-derived cells, namely the establishment of GBM-derived cultures and their maintenance at oxygen tension mimicking oxygenation conditions occurring within the tumour. To globally analyse cell states, we performed the transcriptome analysis of GBM patient-derived cells kept as spheroids in serum-free conditions at the reduced oxygen tension (5% O2), cells cultured at atmospheric oxygen (20% O2), and parental tumour. Immune cells present in the tumour were depleted, resulting in the decreased expression of the immune system and inflammation-related genes. The expression of genes promoting cell proliferation and DNA repair was higher in GBM cell cultures when compared to the relevant tumour sample. However, lowering oxygen tension to 5% did not affect the proliferation rate and expression of cell cycle and DNA repair genes in GBM cell cultures. Culturing GBM cells at 5% oxygen was sufficient to increase the expression of specific stemness markers, particularly the PROM1 gene, without affecting neural cell differentiation markers. GBM spheroids cultured at 5% oxygen expressed higher levels of hypoxia-inducible genes, including those encoding glycolytic enzymes and pro-angiogenic factors. The genes up-regulated in cells cultured at 5% oxygen had higher expression in parental GBMs compared to that observed in 20% cell cultures, suggesting the preservation of the hypoxic component of GBM transcriptome at 5% oxygen and its loss in standard culture conditions. Evaluation of expression of those genes in The Cancer Genome Atlas dataset comprising samples of normal brain tissue, lower-grade gliomas and GBMs indicated the expression pattern of the indicated genes was specific for GBM. Moreover, GBM cells cultured at 5% oxygen were more resistant to temozolomide, the chemotherapeutic used in GBM therapy. The presented comparison of GBM cultures maintained at high and low oxygen tension together with analysis of tumour transcriptome indicates that lowering oxygen tension during cell culture may more allegedly reproduce tumour cell behaviour within GBM than standard culture conditions (e.g., atmospheric oxygen tension). Low oxygen culture conditions should be considered as a more appropriate model for further studies on glioblastoma pathology and therapy. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) is a type of hemoglobinopathy characterized by abnormal hemoglobin molecules, which includes numerous acute and chronic complications. Ischemic stroke, silent cerebral infarction, headache, and neurocognitive impairment are the most common neurological complications associated with SCD. Summary: Acute anemia because of SCD can cause cognitive impairments because of cerebral hypoxia. Cognitive abnormalities in SCD manifest in various aspects such as working memory, verbal learning, executive functions, and attention. These neurocognitive impairments have been associated with poor functional results, such as transitioning from juvenile to adult care, adherence to medications, and unemployment. Key message: In this review, we focus on neurocognitive aspects of SCD patients based on different imaging techniques, psychological batteries, associated neuromarkers, and interventions for managing of cognitive deficiencies.. [ABSTRACT FROM AUTHOR]

Background: Prior studies have investigated the association between duration of resuscitation and short-term outcomes following in-hospital cardiac arrest (IHCA). However, it remains unknown whether there is an association between duration of resuscitation and long-term survival and functional outcomes.Method: We linked data from the Danish in-hospital cardiac arrest registry with nationwide registries and identified 8,727 patients between 2013 and 2019. Patients were stratified into four groups (A-D) according to quartiles of duration of resuscitation. Standardized average probability of outcomes was estimated using logistic regression.Results: Of 8,727 patients, 53.1% (n = 4,604) achieved return of spontaneous circulation. Median age was 74 (1st-3rd quartile [Q1-Q3] 65-81 years) and 63.1% were men. Among all IHCA patients the standardized 30-day survival was 62.0% (95% CI 59.8-64.2%) for group A (<5 minutes), 32.7% (30.8-34.6%) for group B (5-11 minutes), 14.4% (12.9-15.9%) for group C (12-20 minutes) and 8.1% (7.0-9.1%) for group D (21 minutes or more). Similarly, 1-year survival was also highest for group A (50.4%; 48.2-52.6%) gradually decreasing to 6.6% (5.6-7.6%) in group D. Among 30-day survivors, survival without anoxic brain damage or nursing home admission within one-year post-arrest was highest for group A (80.4%; 78.2-82.6%), decreasing to 73.3% (70.0-76.6%) in group B, 67.2% (61.7-72.6%) in group C and 73.3% (66.9-79.7%) in group D.Conclusion: Shorter duration of resuscitation attempt during an IHCA is associated with higher 30-day and 1-year survival. Furthermore, we found that the majority of 30-day survivors were still alive 1-year post-arrest without anoxic brain damage or nursing home admission despite prolonged resuscitation. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate electroencephalogram (EEG) parameters using computerized data processing methods to analyze the possible neurophysiological mechanisms underlying changes seen in patients in the somatogenic phase of acute poisoning with opioid receptor agonists. Materials and methods. The study included 31 patients in the somatogenic phase of acute poisoning with opioid receptor agonists with a level of consciousness of 3–15 points on the Glasgow Coma Scale. EEG recordings were made in accordance with the guidelines of the International Federation of Clinical Neurophysiologists. Indicators of brain electrical activity were analyzed and EEG data were processed by computer (spectral analysis, localization of equivalent dipole sources of pathological brain electrical activity, localization of equivalent current density maxima for EEG oscillations in the neocortex). Results and discussion. The EEG of most (65%, n = 20) patients was dominated by δ-range oscillations. Eight patients showed marked EEG changes, with a maximum amplitude of background oscillations of up to 45–55 μV in the absence of an α rhythm (four patients), though oscillations in the α frequency range could also be present in the EEG with an index of no more than 15–20% of the overall duration of the EEG recording (three patients) and, in one case, bilateral bursts of δ range oscillations (amplitude up to 145 μV) generalized in both hemispheres on this background. Gross EEG changes with diffuse slow-wave activity were detected in 12 patients, with dominance of δ-range index and power. The amplitude of the background δ oscillations was in the range 55–170 μV, reaching 200 μV during bilateral bursts. Conclusions. These results suggest that the EEG changes detected in these patients result from dysfunction of generator mechanisms of both the cortical and the arousal structures of the brain, while the slow-wave, predominantly δ activity, recorded here, taking into account the time the recordings were made (the somatogenic phase), may be due to the actions of secondary modifying factors (hypoxia and cerebral edema). [ABSTRACT FROM AUTHOR]

Background: The hyperventilation test is used in clinical practice for diagnosis and therapeutic purposes; however, in the absence of a standardized protocol, the procedure varies significantly, predisposing tested subjects to risks such as cerebral hypoxia and ischemia. Near-infrared spectroscopy (NIRS), a noninvasive technique performed for cerebral oximetry monitoring, was used in the present study to identify the minimum decrease in the end-tidal CO2 (ETCO2) during hyperventilation necessary to induce changes on NIRS. Materials and Methods: We recruited 46 volunteers with no preexisting medical conditions. Each subject was asked to breathe at a baseline rate (8–14 breaths/min) for 2 min and then to hyperventilate at a double respiratory rate for the next 4 min. The parameters recorded during the procedure were the regional cerebral oxyhemoglobin and deoxyhemoglobin concentrations via NIRS, ETCO2, and the respiratory rate. Results: During hyperventilation, ETCO2 values dropped (31.4 ± 12.2%) vs. baseline in all subjects. Changes in cerebral oximetry were observed only in those subjects (n = 30) who registered a decrease (%) in ETCO2 of 37.58 ± 10.34%, but not in the subjects (n = 16) for which the decrease in ETCO2 was 20.31 ± 5.6%. According to AUC-ROC analysis, a cutoff value of ETCO2 decrease >26% was found to predict changes in oximetry (AUC-ROC = 0.93, p < 0.0001). Seven subjects reported symptoms, such as dizziness, vertigo, and numbness, throughout the procedure. Conclusions: The rise in the respiratory rate alone cannot effectively predict the occurrence of a cerebral vasoconstrictor response induced by hyperventilation, and synchronous ETCO2 and cerebral oximetry monitoring could be used to validate this clinical test. NIRS seems to be a useful tool in predicting vasoconstriction following hyperventilation. [ABSTRACT FROM AUTHOR]

Background: Transcranial color-coded duplex sonography (TCCD) can be used as an ancillary test for determining irreversible loss of brain function (ILBF) when demonstration of cerebral circulatory arrest (CCA) is required. However, visualization of the intracranial vessels by TCCD is often difficult, or even impossible, in this patient cohort due to elevated intracranial pressure, an insufficient transtemporal bone window, or warped anatomical conditions. Since extracranial color-coded duplex sonography (ECCD) can be performed without restriction in the aforementioned situations, we investigated the feasibility of omitting TCCD altogether, such that the ILBF examination would be simplified, without compromising on its reliability. Methods: A total of 122 patients were prospectively examined by two experienced neurointensivists for the presence of ILBF from01/2019-12/2021. Inclusion criteria were (i) the presence of a severe cerebral lesion on cranial CT or MRI, and (ii) brainstem areflexia. Upon standardized clinical examination, 9 patients were excluded due to incomplete brainstem areflexia, and a further 22 due to the presence of factors with a potentially confounding influence on apnea testing, EEG or sonography. A total of 91 patients were enrolled and underwent needle-EEG recording for >30min (= gold standard), as well as ECCD and TCCD. The sonographer was blinded to the EEG result. Results: All patients whose ECCD result was consistent with ILBF had this diagnosis confirmed by EEG (n = 77; specificity: 1). Both ECCD and EEG were not consistent with ILBF in a further 12 patients. In the remaining two patients, ECCD detected reperfusion due to long-lasting cerebral hypoxia; however, ILBF was ultimately confirmed by EEG (sensitivity: 0.975). This yielded a positive predictive value (PPV) of one and a negative predictive value of 0.857 for the validity of ECCD in ILBF confirmation. TCCD was not possible/inconclusive in 31 patients (34%). Conclusions: The use of ECCD for the confirmation of ILBF is associated with high levels of specificity and a high positive predictive value when compared to needle-electrode EEG. Thismakes ECCD a potential alternative to the ancillary tests currently used in this setting, but confirmation in a multi-center trial is warranted. [ABSTRACT FROM AUTHOR]

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones. The probability of cytoprotective action was assessed by measuring cell viability using two tests (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones under the conditions of our experiment had a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones also fully satisfy Lipinski's rule of five (RO5), which increases their chances for possible use as orally active drugs with good absorption ability and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones as having a relatively high cytoprotective potential. [ABSTRACT FROM AUTHOR]

Background: Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, cannabinoid CB2 and serotonin 5HT1A receptors included. These two receptors may interact to form heteromers (CB2–5HT1A-Hets) that are also a target of CBD. Aims: We aimed to assess whether the expression and function of CB2–5HT1A-Hets is affected by CBD in animal models of hypoxia of the neonate and in glucose- and oxygen-deprived neurons. Methods: We developed a quantitation of signal transduction events in a heterologous system and in glucose/oxygen-deprived neurons. The expression of receptors was assessed by immuno-cyto and -histochemistry and, also, by using the only existing technique to visualize CB2–5HT1A-Hets fixed cultured cells and tissue sections (in situ proximity ligation PLA assay). Results: CBD and cannabigerol, which were used for comparative purposes, affected the structure of the heteromer, but in a qualitatively different way; CBD but not CBG increased the affinity of the CB2 and 5HT1A receptor–receptor interaction. Both cannabinoids regulated the effects of CB2 and 5HT1A receptor agonists. CBD was able to revert the upregulation of heteromers occurring when neurons were deprived of oxygen and glucose. CBD significantly reduced the increased expression of the CB2–5HT1A-Het in glucose/oxygen-deprived neurons. Importantly, in brain sections of a hypoxia/ischemia animal model, administration of CBD led to a significant reduction in the expression of CB2–5HT1A-Hets. Conclusions: Benefits of CBD in the hypoxia of the neonate are mediated by acting on CB2–5HT1A-Hets and by reducing the aberrant expression of the receptor–receptor complex in hypoxic-ischemic conditions. These results reinforce the potential of CBD for the therapy of the hypoxia of the neonate. [ABSTRACT FROM AUTHOR]

Intermittent hypoxia, or intermittent low oxygen interspersed with normal oxygen levels, has differential effects that depend on the "dose" of hypoxic episodes (duration, severity, number per day, and number of days). Whereas "low dose" daily acute intermittent hypoxia (dAIH) elicits neuroprotection and neuroplasticity, "high dose" chronic intermittent hypoxia (CIH) similar to that experienced during sleep apnea elicits neuropathology. Sleep apnea is comorbid in >50% of patients with Alzheimer's disease--a progressive, neurodegenerative disease associated with brain amyloid and chronic Tau dysregulation (pathology). Although patients with sleep apnea present with higher Tau levels, it is unknown if sleep apnea through attendant CIH contributes to onset of Tau pathology. We hypothesized CIH characteristic of moderate sleep apnea would increase dysregulation of phosphorylated Tau (phospho-Tau) species in Sprague-Dawley rat hippocampus and prefrontal cortex. Conversely, we hypothesized that dAIH, a promising neurotherapeutic, has minimal impact on Tau phosphorylation. We report a dose-dependent intermittent hypoxia effect, with region-specific increases in 1) phospho-Tau species associated with human Tauopathies in the soluble form and 2) accumulated phospho-Tau in the insoluble fraction. The latter observation was particularly evident with higher CIH intensities. This important and novel finding is consistent with the idea that sleep apnea and attendant CIH have the potential to accelerate the progression of Alzheimer's disease and/or other Tauopathies. NEW & NOTEWORTHY Sleep apnea is highly prevalent in people with Alzheimer's disease, suggesting the potential to accelerate disease onset and/or progression. These studies demonstrate that intermittent hypoxia (IH) induces dose-dependent, region- specific Tau phosphorylation, and are the first to indicate that higher IH "doses" elicit both endogenous, (rat) Tau hyperphosphorylation and accumulation in the hippocampus. These findings are essential for development and implementation of new treatment strategies that minimize sleep apnea and its adverse impact on neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Cerebral hypoxia is a serious consequence of several cardiorespiratory illnesses. Measuring the retinal microvasculature at high altitude provides a surrogate for cerebral microvasculature, offering potential insight into cerebral hypoxia in critical illness. In addition, although sex-specific differences in cardiovascular diseases are strongly supported, few have focused on differences in ocular blood flow. We evaluated the retinal microvasculature in males (n = 11) and females (n = 7) using functional optical coherence tomography at baseline (1,130 m) (day 0), following rapid ascent (day 2), and prolonged exposure (day 9) to high altitude (3,800 m). Retinal vascular perfusion density (rVPD; an index of total blood supply), retinal thickness (RT; reflecting vascular and neural tissue volume), and arterial blood were acquired. As a group, rVPD increased on day 2 versus day 0 (P < 0.001) and was inversely related to PaO2 (R² = 0.45; P = 0.006). By day 9, rVPD recovered to baseline but was significantly lower in males than in females (P = 0.007). RT was not different on day 2 versus day 0 (P > 0.99) but was reduced by day 9 relative to day 0 and day 2 (P < 0.001). RT changes relative to day 0 were inversely related to changes in PaO2 on day 2 (R² = 0.6; P = 0.001) and day 9 (R² = 0.4; P = 0.02). RT did not differ between sexes. These data suggest differential time course and regulation of the retina during rapid ascent and prolonged exposure to high altitude and are the first to demonstrate sex-specific differences in rVPD at high altitude. The ability to assess intact microvasculature contiguous with the brain has widespread research and clinical applications. NEW & NOTEWORTHY Measuring the retinal microvasculature at high altitude provides a surrogate for cerebral microvasculature, offering potential insight into consequence of cerebral hypoxia in critical illness. This study demonstrates dynamic regulation of the retina during rapid ascent and prolonged exposure to high altitude and is the first to demonstrate sex-specific differences in retinal microvasculature at high altitude. The ability to dynamically assess intact microvasculature contiguous with the brain has widespread research and clinical applications. [ABSTRACT FROM AUTHOR]

Despite lack of an evidence basis, the hypothesis that hypoxia causes subdural haemorrhage (SDH) continues to be raised. Recently, the hypothesis included reperfusion after cardiac arrest as a cause of SDH. To determine the incidence of SDH in children under four years old following severe hypoxia and subsequent reperfusion, fatal drownings in children under four years old who were autopsied between 1974 through 1995 in the Western Washington Drowning Database were reviewed. A total of 88 drowning deaths were identified. Their median age was 2.0 years; 11 per cent (10/88) were under one year old. Fifty‐three per cent (47/88) died in the field and 47 per cent (41/88) had temporary return of spontaneous circulation. SDH was identified in none of the children. Intracranial haemorrhage was identified in two children: subarachnoid haemorrhage was found in a neonate who drowned right after birth; the second was an epidural bleed directly below a surgical burr hole. This study provides additional evidence that SDH is not caused by severe hypoxia and reperfusion events. [ABSTRACT FROM AUTHOR]

Introduction: Acute high‐altitude hypoxia exposure causes multiple adverse neurological consequences. However, the exact mechanisms are still unclear, and there is no targeted treatment with few side effects. Excessive cerebral formaldehyde (FA) impairs numerous functions, and can be eliminated by nano‐packed coenzyme Q10 (CoQ10). Aims: In this study, we aimed to investigate whether cerebral FA was accumulated after hypobaric hypoxia exposure, and further explored the preventative effect of CoQ10 through FA elimination. Results: Accumulated cerebral FA was found in C57BL/6 mice after acute high‐altitude hypoxia exposure, which resulted in FA metabolic disturbance with the elevation of semicarbazide‐sensitive amine oxidase, and declination of aldehyde dehydrogenase‐2. Excessive FA was also found to induce neuronal ferroptosis in vivo. Excitingly, administration with CoQ10 for 3 days before acute hypobaric hypoxia reduced cerebral FA accumulation, alleviated subsequent neuronal ferroptosis, and preserved neurological functions. Conclusion: Cerebral FA accumulation mediates neurological deficits under acute hypobaric hypoxia, and CoQ10 supplementation may be a promising preventative strategy for visitors and sojourners at plateau. [ABSTRACT FROM AUTHOR]

Based on the MRI, cell therapy was not able to significantly reduce the infarct size; however, treatment with MSCs provided protection from MBP degradation indicating attenuation of white matter loss 28 days after ischemia. Although reports on this method of cell delivery are mainly centered around the therapeutic consequences of the cell therapy, few studies focused on the pathways by which intranasally applied cells enter the brain. At day 28 post-stroke, the cell therapy had increased the number of EdU and BrdU-positive cells in the ipsilateral striatum, near the ischemic boundary zone, indicating an enhancement of endogenous cell proliferation. Beneficial potential of neural stem cells (NSCs) in cell therapy after ischemia Although MSCs are considered the most commonly employed stem cell type for cell-based therapies in general, and the field of cerebral hypoxia/ischemia in particular, the curative potential of NSC is gaining interest. Keywords: conditioned medium; hypoxic brain; ischemic brain; nasal delivery; secretome; stem cell EN conditioned medium hypoxic brain ischemic brain nasal delivery secretome stem cell 583 606 24 08/09/22 20220801 NES 220801 Introduction Cerebral ischemia and hypoxic brain damage are devastating conditions that are considered as major global problems. [Extracted from the article]

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, with typical motor symptoms as the main clinical manifestations. At present, there are about 10 million patients with PD in the world, and its comorbidities and complications are numerous and incurable. Therefore, it is particularly important to explore the pathogenesis of PD and find possible therapeutic targets. Because the etiology of PD is complex, involving genes, environment, and aging, finding common factors is the key to identifying intervention targets. Hypoxia is ubiquitous in the natural environment and disease states, and it is considered to be closely related to the etiology of PD. Despite research showing that hypoxia increases the expression and aggregation of alpha-synuclein (a-syn), the most important pathogenic protein, there is still a lack of systematic studies on the role of hypoxia in a-syn pathology and PD pathogenesis. Considering that hypoxia is inextricably linked with various causes of PD, hypoxia may be a co-participant in many aspects of the PD pathologic process. In this review, we describe the risk factors for PD, and we discuss the possible role of hypoxia in inducing PD pathology by these risk factors. Furthermore, we attribute the pathological changes caused by PD etiology to oxygen uptake disorder and oxygen utilization disorder, thus emphasizing the possibility of hypoxia as a critical link in initiating or promoting a-syn pathology and PD pathogenesis. Our study provides novel insight for exploring the pathogenesis and therapeutic targets of PD. [ABSTRACT FROM AUTHOR]

Differential gene expression normalised to a single housekeeping (HK) is used to identify disease mechanisms and therapeutic targets. HK gene selection is often arbitrary, potentially introducing systematic error and discordant results. Here we examine these risks in a disease model of brain hypoxia. We first identified the eight most frequently used HK genes through a systematic review. However, we observe that in both ex-vivo and in vivo, their expression levels varied considerably between conditions. When applying these genes to normalise expression levels of the validated stroke target gene, inducible Nox4, we obtained opposing results. As an alternative tool for unbiased HK gene selection, software tools exist but are limited to individual datasets lacking genome-wide search capability and user-friendly interfaces. We, therefore, developed the HouseKeepR algorithm to rapidly analyse multiple gene expression datasets in a disease-specific manner and rank HK gene candidates according to stability in an unbiased manner. Using a panel of de novo top-ranked HK genes for brain hypoxia, but not single genes, Nox4 induction was consistently reproduced. Thus, differential gene expression analysis is best normalised against a HK gene panel selected in an unbiased manner. HouseKeepR is the first user-friendly, bias-free, and broadly applicable tool to automatically propose suitable HK genes in a tissue- and disease-dependent manner. [ABSTRACT FROM AUTHOR]

Brain tissue oxygenation (PbtO2)-guided therapy can improve the neurological outcome of traumatic brain injury (TBI) patients. With several Phase-III ongoing studies, most of the existing evidence is based on before-after cohort studies and a phase-II randomized trial. The aim of this study was to assess the effectiveness of PbtO2-guided therapy in a single-center cohort. We performed a retrospective analysis of consecutive severe TBI patients admitted to our center who received either intracranial pressure (ICP) guided therapy (from January 2012 to February 2016) or ICP/PbtO2-guided therapy (February 2017 to December 2019). A genetic matching was performed based on covariates including demographics, comorbidities, and severity scores on admission. Intracranial hypertension (IH) was defined as ICP > 20 mmHg for at least 5 min. Brain hypoxia (BH) was defined as PbtO2 < 20 mmHg for at least 10 min. IH and BH were targeted by specific interventions. Mann–Whitney U and Fisher's exact tests were used to assess differences between groups. A total of 35 patients were matched in both groups: significant differences in the occurrence of IH (ICP 85.7% vs. ICP/PbtO2 45.7%, p < 0.01), ICU length of stay [6 (3–13) vs. 16 (9–25) days, p < 0.01] and Glasgow Coma Scale at ICU discharge [10 (5–14) vs. 13 (11–15), p = 0.036] were found. No significant differences in ICU mortality and Glasgow Outcome Scales at 3 months were observed. This study suggests that the role of ICP/PbtO2-guided therapy should await further confirmation in well-conducted large phase III studies. [ABSTRACT FROM AUTHOR]

(1) Background: Despite the improvement of the in-hospital survival rate after aborted sudden cardiac death (SCD), cerebral anoxia may have severe neurologic consequences and may impair long-term outcome and quality of life of surviving patients. The aim of this study was to assess neurological outcomes at one year after resuscitated cardiac arrest; (2) Methods: This prospective, observational, and multicentre study included patients >18 yo admitted in the catheterisation laboratory for coronary angiography after aborted SCD between 1 May 2018 and 31 May 2020. Only patients who were discharged alive from hospital were evaluated. The primary endpoint was survival without neurological sequelae at one-year follow-up defined by a cerebral performance category (CPC) of one or two. Secondary end points included all-cause mortality, New York Heart Association (NYHA) functional class, neurologic evaluation at discharge, three-month and one-year follow-up using the CPC scale, and quality of life at 1 year using the Quality of Life after Brain Injury (QOLIBRI) questionnaire; (3) Results: Among 143 patients admitted for SCD within the study period, 61 (42.7%) were discharged alive from hospital, among whom 55 (90.1%) completed the one-year follow-up. No flow and low flow times were 1.9 ± 2.4 min and 16.5 ± 10.4 min, respectively. For 93.4% of the surviving patients, an initial shockable rhythm (n = 57) was observed and acute coronary syndrome was diagnosed in 75.4% of them (n = 46). At 1 year, survival rate without neurologic sequelae was 87.2% (n = 48). Patients with poor outcome were older (69.3 vs. 57.4 yo; p = 0.04) and had lower body mass index (22.4 vs. 26.7; p = 0.013) and a lower initial Left Ventricle Ejection Fraction (LVEF) (32.1% vs. 40.3%; p = 0.046). During follow-up, neurological status improved in 36.8% of patients presenting sequelae at discharge, and overall quality of life was satisfying for 66.7% of patients according to the QOLIBRI questionnaire; (4) Conclusions: Among patients admitted to the catheterisation laboratory for aborted SCD, mainly related to Acute Coronary Syndrom (ACS), less than a half of them were alive at discharge. However, the one-year survival rate without neurological sequelae was high and overall quality of life was good. [ABSTRACT FROM AUTHOR]

Introduction  Bilirubin has been found to be a natural antioxidant protecting the body from oxidative stress. This study aims to investigate the severity of neonatal hypoxic injury on bilirubin levels to clarify the physiological role of bilirubin. Study Design  Using lactate as a biomarker for the severity of hypoxic injury, we retrospectively analyzed the association of admission lactate levels on serum total bilirubin (TB) levels following birth in neonates with hypoxic–ischemic encephalopathy (HIE). We created a univariate linear regression model to predict TB using the admission lactate level as a predictor. We also performed a multivariate linear regression analysis to predict TB with admission lactate levels that included phenobarbital cumulative dosage, admission hematocrit, and subgaleal hemorrhage as predictor variables. Results  A total of 86 patients were studied. Admission lactate levels had a significant negative effect on TB from admission to 3 days of life. The standardized regression coefficient for admission lactate on TB was −0.37 (admission), −0.42 (day 1), −0.32 (day 2), and −0.28 (day 3). A similar negative effect of admission lactate on TB levels was also observed in the multivariate linear regression model even after controlling for the other variables. Conclusion  These results are consistent with the hypothesis that bilirubin functions as an antioxidant in vivo, and is consumed by scavenging free radicals in proportion to the severity of hypoxic injury. Key Points Lactate levels have a negative effect on serum TB levels in patients with neonatal HIE. Bilirubin might work as a natural antioxidant to protect the body from oxidative stress. Serum TB might be a marker for the severity of hypoxic injury. [ABSTRACT FROM AUTHOR]

Objectives Methadone is a kind of opioid that is used to reduce the pain of addicts who decide to withdraw drugs. Sometimes due to a lack of appropriate cautions, this drug will be accessible to children, and poisoning might occur. Methadone poisoning usually presents with the loss of consciousness and pinpoint pupils. Herein, we present two cases of delayed hypoxic encephalopathy that had been poisoned by methadone. Case Presentation The first case was a 4-year-old female patient who firstly presented with nausea and vomiting; then, the case was discharged; however, 1 week later, the case was returned with the loss of consciousness and poisoning by methadone confirmed in her urine. Again 2 weeks later, the case returned to the hospital, developing weakness of limbs, slurred speech, and abnormal movement of her limbs. The second case was an 11-year-old female patient who was admitted to an intensive care unit due to the loss of consciousness and methadone poisoning. After providing supporting care, she was discharged but returned to the hospital 5 days later. She developed weakness of limbs, abnormal movement of tongue and extremities, and slurred speech. In their last admission, the magnetic resonance imaging of the patients revealed hypoxic damage in the basal ganglia; therefore, delayed hypoxic encephalopathy was confirmed. Conclusion Patients with methadone poisoning should be observed for at least 1 and a half months after poisoning. Moreover, parents should notice that in the case of observing abnormal neurologic manifestations bring their child as soon as possible to a hospital to prevent irreversible damage to the brain. [ABSTRACT FROM AUTHOR]

Previous reports have indicated that natural muscone has neuroprotective effects against cerebral hypoxia injury; however, little is known in regards to its pharmacological mechanism. In this study, we tried to evaluate the neuroprotective effects and mechanisms of muscone against cerebral hypoxia injury using an in vitro model. The cerebral hypoxia injury cell model was produced by hypoxia/reoxygenation (H/R). The cell viability and apoptosis were measured using the cell counting Kit-8 and the Annexin V-FITC/PI Apoptosis Detection kit, respectively. To screen microRNAs regulated by muscone, we analyzed the gene expression datasets of GSE84216 retrieved from gene expression omnibus (GEO). Here, it was demonstrated that muscone treatment significantly alleviated the cell apoptosis, oxidative stress and inflammation in H/R-exposed neurons. Subsequently, through analyzing GSE84216 from the GEO database, miR-142-5p was markedly upregulated by treatment of muscone in this cell model of cerebral hypoxia injury. Further experiments revealed that downregulation of miR-142-5p eliminated the neuroprotective effects of muscone against H/R induced neuronal injury. Additionally, high mobility group box 1 (HMGB1), an important inflammatory factor, was identified as a direct target of miR-142-5p in neurons. Meanwhile, we further demonstrated that muscone could reduce the expression of HMGB1 by upregulating miR-142-5p expression, which subsequently resulted in the inactivation of TLR4/NF-B pathway, finally leading to the improvement of cell injury in H/Rexposed neurons. Overall, we demonstrate for the first time that muscone treatment alleviates cerebral hypoxia injury in in vitro experiments through blocking activation of the TLR4/NF-B signaling pathway by targeting HMGB1, suggesting that muscone may serve as a potential therapeutic drug for treating cerebral hypoxia injury. [ABSTRACT FROM AUTHOR]

Objective: In this study, we assessed the correlation between the lactate dehydrogenase (LDH) to phosphate ratio and the prognosis of microsurgical clippings for ruptured intracranial aneurysm (rIA) to test the hypothesis that the serum LDH to phosphate ratio could be a predictor of the outcome of microsurgical clipping for rIA. Methods: Records of rIA patients between 2012 and 2018 were retrospectively collected. Age, sex, Hunt-Hess grade, Fisher grade, medical history, aneurysm location, hydrocephalus, laboratory data including serum LDH, phosphate, and LDH to phosphate ratio, related complications, and the outcomes in 3 months were recorded. Results: A total of 1608 rIA patients in our institution were collected, and 856 patients treated by microsurgical clipping were enrolled. On admission, a significantly higher LDH-phosphate ratio was observed in patients with poor outcomes at 3 months (median ± SD, 200.175 ± 107.290 for mRS 0–2 vs. 323.826 ± 219.075 for mRS score 3–6; p = 0.000). An LDH to phosphate ratio of 226.25 in the receiver operating characteristic (ROC) curve was the optimal cutoff value to discriminate between good and poor outcomes at 3 months. The LDH to phosphate ratio ≥ 226.25 on admission was independently correlated with poor outcomes in rIA patients. In addition, Hunt and Hess grade, Fisher grade, pneumonia, and DIND were also independently correlated with poor outcomes. After removing the bias in essential clinical variables between patients with LDH to phosphate, ratio ≥ 226.25 versus <226.25 by PSM, the number of patients with poor outcomes at 3 months increased in patients with an LDH to phosphate ratio of ≥226.25 (p = 0.005). Conclusions: The LDH to phosphate ratio was a potential biomarker and could predict the unfavorable outcome of microsurgical clipping for rIA in 3 months, related to neuronal damage, cerebral hypoxia, and early brain injury after aneurysm ruptures. [ABSTRACT FROM AUTHOR]

Objectives: Anemia is common after acute brain injury and can be associated with brain tissue hypoxia. RBC transfusion (RBCT) can improve brain oxygenation; however, predictors of such improvement remain unknown. We aimed to identify the factors associated with PbtO2 increase (greater than 20% from baseline value) after RBCT, using a generalized mixed model.Design: This is a multicentric retrospective cohort study (2012-2020).Setting: This study was conducted in three European ICUs of University Hospitals located in Belgium, Switzerland, and Austria.Patients: All patients with acute brain injury who were monitored with brain tissue oxygenation (PbtO2) catheters and received at least one RBCT.Intervention: Patients received at least one RBCT. PbtO2 was recorded before, 1 hour, and 2 hours after RBCT.Measurements and Main Results: We included 69 patients receiving a total of 109 RBCTs after a median of 9 days (5-13 d) after injury. Baseline hemoglobin (Hb) and PbtO2 were 7.9 g/dL [7.3-8.7 g/dL] and 21 mm Hg (16-26 mm Hg), respectively; 2 hours after RBCT, the median absolute Hb and PbtO2 increases from baseline were 1.2 g/dL [0.8-1.8 g/dL] (p = 0.001) and 3 mm Hg (0-6 mm Hg) (p = 0.001). A 20% increase in PbtO2 after RBCT was observed in 45 transfusions (41%). High heart rate (HR) and low PbtO2 at baseline were independently associated with a 20% increase in PbtO2 after RBCT. Baseline PbtO2 had an area under receiver operator characteristic of 0.73 (95% CI, 0.64-0.83) to predict PbtO2 increase; a PbtO2 of 20 mm Hg had a sensitivity of 58% and a specificity of 73% to predict PbtO2 increase after RBCT.Conclusions: Lower PbtO2 values and high HR at baseline could predict a significant increase in brain oxygenation after RBCT. [ABSTRACT FROM AUTHOR]

• Isolated triad findings will no longer by default be classified as caused by SBS/AHT. • Revival shaking attempts will be considered as a benevolent action, not as abuse. • The number of innocent caregivers who are currently considered as lying perpetrators, will decrease. • Presumed innocence and the rule of law will prevail. During the 1980′s a sudden life-lessness attack in a very young infant was described as "near-SIDS", and a caregiver who observed and tried to revive the infant was considered to be reliable and honourable. If, after the later acceptance of the traditional shaken baby theory, bilateral thin subdural hemorrhages (SDH) and retinal hemorrhages (RH) are detected after a lifelessness attack such a reliable caregiver has by default been transformed into an unreliable perpetrator of violent shaking. In 2016, the term "near-SIDS" was – via "apparent life-threatening event" (ALTE) − replaced by "brief resolved unexplained event" (BRUE). We suggest that such a life-threatening event is not always brief, and not always resolved. Based on a neglected hypoxia theory from 2004 we suggest as a hypothesis that a prolonged episode of apnea can result in brain hypoxia, brain edema, SDH, RH and increased intracranial pressure. The new hypothesis includes two new concepts: Prolonged Non-fatal Unexplained Event (PNUE) and Prolonged Fatal Unexplained Event (PFUE) which together with the hypoxia theory might explain why these two separate diagnoses have been conflated into one, viz. shaken baby syndrome (SBS). We suggest a study design that might corroborate or falsify the hypothesis, and if our hypothesis is corroborated, current "unreliable perpetrators" could be re-established as reliable resuscitators. [ABSTRACT FROM AUTHOR]

Sevoflurane postconditioning has been shown to provide neuroprotection against cerebral hypoxia-ischemia injury, but the mechanisms remain elusive. Microtubule-associated protein 2 (MAP2) is implicated in early neuronal hypoxia-ischemia injury. This study aimed to investigate whether the neuroprotective effects of sevoflurane postconditioning are related to the Akt/GSK-3β pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3β inhibitor TDZD-8 were used to treat H/R zebrafish. The cerebral infarction, neuronal apoptosis, and mitochondrial changes were evaluated using TTC staining, TUNEL staining, and transmission electron microscopy, respectively. The distribution of MAP2 in the brain was determined by immunofluorescence imaging. The levels of Akt, p-Akt, GSK-3β, p-GSK-3β, and MAP2 proteins were evaluated by Western blotting. The neurobehavioral recovery of zebrafish was assessed based on optokinetic response behavior. Our results indicated that sevoflurane postconditioning and TDZD-8 significantly reduced the cerebral infarction area, suppressed cell apoptosis, and improved mitochondrial integrity in zebrafish subjected to H/R. Furthermore, sevoflurane postconditioning and TDZD-8 elevated the ratios of p-Akt/Akt and p-GSK-3β/GSK-3β. However, the neuroprotective effect of sevoflurane postconditioning was effectively abolished upon suppression of MAP2 expression. In conclusion, sevoflurane postconditioning ameliorated cerebral H/R injury and facilitated the restoration of neurobehavioral function through the activation of Akt/GSK-3β pathway and promotion of MAP2 expression. [Display omitted] • Sevoflurane postconditioning attenuated cerebral infarction and apoptosis. • Sevoflurane postconditioning improved neuron mitochondrial morphology integrity. • Sevoflurane postconditioning promoted optokinetic response behavior recovery. • Sevoflurane neuroprotection was mediated by activating Akt/GSK-3β and promoting MAP2. [ABSTRACT FROM AUTHOR]

Mitochondrial dysmorphology/dysfunction follow global cerebral ischemia-reperfusion (GCI/R) injury, leading to neuronal death. Our previous researches demonstrated that Levodopa (L-DOPA) improves learning and memory impairment in GCI/R rats by increasing synaptic plasticity of hippocampal neurons. This study investigates if L-DOPA, used in Parkinson's disease treatment, alleviates GCI/R-induced cell death by enhancing mitochondrial quality. Metabolomics and transcriptomic results showed that GCI/R damage affected the Tricarboxylic acid (TCA) cycle in the hippocampus. The results of this study show that L-DOPA stabilized mitochondrial membrane potential and ultrastructure in hippocampus of GCI/R rats, increased dopamine level in hippocampus, decreased succinic acid level, and stabilized Ca2+ level in CA1 subregion of hippocampus. As a precursor of dopamine, L-DOPA is presumed to improves mitochondrial function in hippocampus of GCI/R rats. However, dopamine cannot cross the blood-brain barrier, so L-DOPA is used in clinical therapy to supplement dopamine. In this investigation, OGD/R models were established in isolated mouse hippocampal neurons (HT22) and primary rat hippocampal neurons. Notably, dopamine exhibited a multifaceted impact, demonstrating inhibition of mitochondrial reactive oxygen species (mitoROS) production, stabilization of mitochondrial membrane potential and Ca2+ level, facilitation of TCA circulation, promotion of aerobic respiratory metabolism, and downregulation of succinic acid-related gene expression. Consistency between in vitro and in vivo results underscores dopamine's significant neuroprotective role in mitigating mitochondrial dysfunction following global cerebral hypoxia and ischemia injury. Supplement dopamine may represent a promising therapy to the cognitive impairment caused by GCI/R injury. [Display omitted] • GCI/R causes hippocampal mitochondrial respiratory dysfunction. • L-DOPA or dopamine stabilizes Ca2+ level, the mitochondrial structure and function in the hippocampus of GCI/R-injured rats. • L-DOPA or dopamine is a potential novel mitochondrial regulator. • Supplement dopamine may represent a promising therapy to the cognitive impairment caused by GCI/R injury. [ABSTRACT FROM AUTHOR]

KAT Gcn5 and DUB Ubp8 are required for respiration and mitochondria functions in budding yeast, and in this study we show that loss of respiratory activity is acquired over time. Interestingly, we show that absence of Ubp8 allows cells to grow in hypoxic conditions with altered mitophagy. Comparatively, the aggressive glioblastoma (GBM) multiforme tumor shows survival mechanisms able to overcome hypoxia in the brain. Starting from yeast and our findings on the role of Ubp8 in hypoxia, we extended our analysis to the human ortholog and signature cancer gene Usp22 in glioblastoma tumor specimens. Here we demonstrate that Usp22 is localized and overexpressed in the pseudo-palisade tissue around the necrotic area of the tumor. In addition, Usp22 colocalizes with the mitophagy marker Parkin, indicating a link with mitochondria function in GBM. Collectively, this evidence suggests that altered expression of Usp22 might provide a way for tumor cells to survive in hypoxic conditions, allowing the escape of cells from the necrotic area toward vascularized tissues. Collectively, our experimental data suggest a model for a possible mechanism of uncontrolled proliferation and invasion in glioblastoma. [ABSTRACT FROM AUTHOR]

Most SARS CoV-2 infections probably occur unnoticed or cause only cause a mild common cold that does not require medical intervention. A significant proportion of more severe cases is characterized by early neurological symptoms such as headache, fatigue, and impaired consciousness, including respiratory distress. These symptoms suggest hypoxia, specifically affecting the brain. The condition is best explained by primary replication of the virus in the nasal respiratory and/or the olfactory epithelia, followed by an invasion of the virus into the central nervous system, including the respiratory centers, either along a transneural route, through disruption of the blood-brain barrier, or both. In patients, presenting with early dyspnea, the primary goal of therapy should be the reversal of brain hypoxia as efficiently as possible. The first approach should be intermittent treatment with 100% oxygen using a tight oronasal mask or a hood. If this does not help within a few hours, an enclosure is needed to increase the ambient pressure. This management approach is well established in the hypoxia-related diseases in diving and aerospace medicine and preserves the patient's spontaneous breathing. Preliminary research evidence indicates that even a small elevation of the ambient pressure might be lifesaving. Other neurological symptoms, presenting particularly in long COVID-19, suggest imbalance of the autonomous nervous system, i.e., dysautonomia. These patients could benefit from vagal nerve stimulation. [ABSTRACT FROM AUTHOR]

Background: Analysis of intracranial multimodality monitoring data is challenging, and quantitative methods may help identify unique physiological signatures that inform therapeutic strategies and outcome prediction. The aim of this study was to test the hypothesis that data-driven approaches can identify distinct physiological states from intracranial multimodality monitoring data. Methods: This was a single-center retrospective observational study of patients with either severe traumatic brain injury or high-grade subarachnoid hemorrhage who underwent invasive multimodality neuromonitoring. We used hierarchical cluster analysis to group hourly values for heart rate, mean arterial pressure, intracranial pressure, brain tissue oxygen, and cerebral microdialysis across all included patients into distinct groups. Average values for measured physiological variables were compared across the identified clusters, and physiological profiles from identified clusters were mapped onto physiological states known to occur after acute brain injury. The distribution of clusters was compared between patients with favorable outcome (discharged to home or acute rehab) and unfavorable outcome (in-hospital death or discharged to chronic nursing facility). Results: A total of 1704 observations from 20 patients were included. Even though the difference in mean values for measured variables between patients with favorable and unfavorable outcome were small, we identified four distinct clusters within our data: (1) events with low brain tissue oxygen and high lactate-to-pyruvate ratio–values (consistent with cerebral ischemia), (2) events with higher intracranial pressure values without evidence for ischemia (3) events which appeared to be physiologically "normal," and (4) events with high cerebral lactate without brain hypoxia (consistent with cerebral hyperglycolysis). Patients with a favorable outcome had a greater proportion of cluster 3 (normal) events, whereas patients with an unfavorable outcome had a greater proportion of cluster 1 (ischemia) and cluster 4 (hyperglycolysis) events (p < 0.0001, Fisher–Freeman–Halton test). Conclusions: A data-driven approach can identify distinct groupings from invasive multimodality neuromonitoring data that may have implications for therapeutic strategies and outcome predictions. These groupings could be used as classifiers to train machine learning models that can aid in the treatment of patients with acute brain injury. Further work is needed to replicate the findings of this exploratory study in larger data sets. [ABSTRACT FROM AUTHOR]

Children with acute neurologic illness are at high risk of mortality and long-term neurologic disability. Severe traumatic brain injury, cardiac arrest, stroke, and central nervous system infection are often complicated by cerebral hypoxia, hypoperfusion, and edema, leading to secondary neurologic injury and worse outcome. Owing to the paucity of targeted neuroprotective therapies for these conditions, management emphasizes close physiologic monitoring and supportive care. In this review, we will discuss advanced neurologic monitoring strategies in pediatric acute neurologic illness, emphasizing the physiologic concepts underlying each tool. We will also highlight recent innovations including novel monitoring modalities, and the application of neurologic monitoring in critically ill patients at risk of developing neurologic sequelae. [ABSTRACT FROM AUTHOR]

Survivors of an out-of-hospital cardiac arrest are at a high risk of mortality and morbidity especially when there is resultant global hypoxic brain injury. In these situations, the patient's degree of neurologic recovery may be uncertain and family decision making is often difficult. Decision making may also be complicated by the age of the patient and one's underlying cultural and spiritual beliefs stressing the importance of patient- and family-centered care. In this article, this clinical case demonstrates the challenges in decision making and highlights the importance of communication among the health care team and the family to align the patient's goals, values, and preferences in light of a poor neurological prognosis. [ABSTRACT FROM AUTHOR]

Background: Although the effect of Erythropoietin (EPO) in neonatal and animal model of hypoxic ischemic encephalopathy has been previously reported, its effect on comatose patients in adult human has yet to be investigated. Methods: This study was designed to find the effect of intravenous administration of EPO on the recovery from coma in the adult patients with Cardiac Arrest (CA)-induced hypoxic ischemic encephalopathy. This randomized controlled trial study was performed on 60 CA patients who survived Cardiopulmonary Resuscitation (CPR) from April 2011 to Nov 2020. The patients were randomly divided into two equal groups including the control, received normal saline, and the EPO groups, and demographic data were recorded. The EEG and Glasgow Coma Scale (GCS) were recorded on hours 6, 12, 24, and 48 post-success CPR and interpreted by an expert neurologist. Magnetic Resonance Imaging (MRI) was done at 24 and 72 hr of post-CPR and interpreted by an expert radiologist. All patients were checked twice daily by an expert cardiologist. Results: 60 patients were included in this study. There was no significant difference between two groups in terms of demographic data. There was also no significant difference between two groups in terms of GCS and EEG at all post-CPR interval times. No significant difference was observed between both groups with respect to the frequency of pre-existing and metabolic acid-base disorders. Conclusion: The intravenous administration of EPO has no effect on the recovery from coma in the adult patients with CA-induced hypoxic ischemic encephalopathy. [ABSTRACT FROM AUTHOR]

Background: Brain tissue hypoxia is a common consequence of traumatic brain injury (TBI) due to the rupture of blood vessels during impact and it correlates with poor outcome. The current magnetic resonance imaging (MRI) techniques are unable to provide a direct map of tissue hypoxia. Purpose To investigate whether GdDO3NI, a nitroimidazole‐based T1 MRI contrast agent allows imaging hypoxia in the injured brain after experimental TBI. Study Type: Prospective. Animal Model: TBI‐induced mice (controlled cortical impact model) were intravenously injected with either conventional T1 agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n = 5 for each cohort) along with pimonidazole (60 mg/kg) at 1 hour postinjury and imaged for 3 hours following which they were euthanized. Field Strength/Sequence: 7 T/T2‐weighted spin echo and T1‐weighted gradient echo. Assessment Injured animals were imaged with T2‐weighted spin‐echo sequence to estimate the extent of the injury. The mice were then imaged precontrast and postcontrast using a T1‐weighted gradient‐echo sequence for 3 hours postcontrast. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post‐imaging for immunohistochemical analysis. Statistical Tests: One‐way analysis of variance and two‐sample t‐tests were performed with a P < 0.05 was considered statistically significant. Results: GdDO3NI retention in the injury region at 2.5–3 hours post‐injection was significantly higher compared to gadoteridol (mean retention fraction 63.95% ± 27.43% vs. 20.68% ± 7.43% for gadoteridol at 3 hours) while it rapidly cleared out of the muscle region. Pimonidazole staining confirmed the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort showed good agreement with MRI contrast enhancement. Data Conclusion: GdDO3NI was successfully shown to visualize hypoxia in the brain post‐TBI using T1‐weighted MRI at 2.5–3 hours postcontrast. Evidence Level 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Developing a novel tool capable of real‐time monitoring and simultaneous quantitation of multiple molecules in mitochondria across the whole brain of freely moving animals is the key bottleneck for understanding the physiological and pathological roles that mitochondria play in the brain events. Here we built a Raman fiber photometry, and created a highly selective non‐metallic Raman probe based on the triple‐recognition strategies of chemical reaction, charge transfer, and characteristic fingerprint peaks, for tracking and simultaneous quantitation of mitochondrial O2.−, Ca2+ and pH at the same location in six brain regions of free‐moving animal upon hypoxia. It was found that mitochondrial O2.−, Ca2+ and pH changed from superficial to deep brain regions upon hypoxia. It was discovered that hypoxia‐induced mitochondrial O2.− burst was regulated by ASIC1a, leading to mitochondrial Ca2+ overload and acidification. Furthermore, we found the overload of mitochondrial Ca2+ was mostly attributed to the influx of extracellular Ca2+. [ABSTRACT FROM AUTHOR]

The article aims to raise awareness of suicide through a discussion about a severely abnormal electroencephalogram (EEG) recording of a patient in her mid-40s who was found unresponsive after a suicide-attempt by helium inhalation. Topics covered include an evaluation of the patient's brain dysfunction, depth of coma, possible non-convulsive status epilepticus, and reactivity found by the EEG, a discussion of the EEG findings, and patient outcome following treatment.

Shoulder dystocia, or shoulder entrapment at birth, is an obstetrician's nightmare, which not infrequently leads to court litigation with complaints of serious foetal and/or maternal damage. Increasingly, retrospective management scrutiny is extending well beyond second stage birth mechanics and involving all case file entries, history taking, ultrasound scan measurements and haematology profile results, etc. The article highlights some medico-legal issues including the influence of the Montgomery ruling on patient disclosure and subsequent management. [ABSTRACT FROM AUTHOR]

Autoerotic asphyxia is defined as a self-induced cerebral anoxia in an autoerotic context. This practice is used to induce a state of hypoxia to elicit or enhance sexual excitement and orgasm. Autoerotic deaths are very rare events and include different mechanism such as asphyxia by hanging, ligature or electrocution, overdressing wrapping and more. According to the literature, male subjects are reported as the main victims of these events. In this paper we describe an interesting case of a 54-year-old Italian man, who accidentally deceased by placing a hemp rope around his neck during autoerotic asphyxial activities. The rope examination revealed an interesting safety mechanism: a means to adjust its diameter through a supplementary rope. [ABSTRACT FROM AUTHOR]