Phase-Change Based Oxygen Carriers Improve Acute Cerebral Hypoxia.

Stroke is the second leading cause of death worldwide, and hypoxia is a major crisis of the brain after stroke. Therefore, providing oxygen to the brain microenvironment can effectively protect neurons from damage caused by cerebral hypoxia. However, there is a lack of timely and effective means of oxygen delivery clinically to the brain for acute cerebral hypoxia. Here, a phase-change based nano oxygen carrier is reported, which can undergo a phase change in response to increasing temperature in the brain, leading to oxygen release. The nano oxygen carrier demonstrate intracerebral oxygen delivery capacity and is able to release oxygen in the hypoxic and inflammatory region of the brain. In the acute ischemic stroke mouse model, the nano oxygen carrier can effectively reduce the area of cerebral infarction and decrease the level of inflammation triggered by cerebral hypoxia. By taking advantage of the increase in temperature during cerebral hypoxia, phase-change oxygen carrier proposes a new intracerebral oxygen delivery strategy for reducing acute cerebral hypoxia.

Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review.

This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series of molecular changes, and explores the causal relationship between these changes and neuronal functional impairment. As a severe pathological condition, cerebral hypoxia can significantly alter the morphology and function of neurons and dendritic spines. Specifically, dendritic spines, being the critical structures for neurons to receive information, undergo changes such as a reduction in number and morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading to neurotransmission disorders. This article delves into the roles of molecular pathways like MAPK, AMPA receptors, NMDA receptors, and BDNF in the hypoxia-induced changes in neurons and dendritic spines, and outlines current treatment strategies. Neurons are particularly sensitive to cerebral hypoxia, with their apical dendrites being vulnerable to damage, thereby affecting cognitive function. Additionally, astrocytes and microglia play an indispensable role in protecting neuronal and synaptic structures, regulating their normal functions, and contributing to the repair process following injury. These studies not only contribute to understanding the pathogenesis of related neurological diseases but also provide important insights for developing novel therapeutic strategies. Future research should further focus on the dynamic changes in neurons and dendritic spines under hypoxic conditions and their intrinsic connections with cognitive function.

Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2 ), and, in some protocols, brain tissue PO2 , by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2 , rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg-1 min-1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO2 , but increased renal cortical and medullary PO2 . Increasing blood haemoglobin concentration increased rSO2 , but not renal PO2 . We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.

Letter to editor: Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis of published cases.

This critique evaluates a letter to the editor discussing the role of brain tissue oxygen partial pressure (PbtO2) monitoring in the prognosis of patients with traumatic brain injury (TBI). The meta-analysis aims to synthesize existing evidence, highlighting the potential of PbtO2 monitoring as an early indicator of cerebral hypoxia and its correlation with improved patient outcomes. Despite these promising findings, the analysis is constrained by significant methodological variability among the included studies, potential publication bias, and the practical challenges of implementing PbtO2 monitoring widely. The letter emphasizes the need for standardized protocols and further research to solidify the clinical utility of PbtO2 monitoring and integrate it with other monitoring strategies for comprehensive TBI management.

Brain Oxygenation Response to Hypercapnia in Patients with Acute Brain Injury.

BACKGROUND: Cerebral hypoxia is a frequent cause of secondary brain damage in patients with acute brain injury. Although hypercapnia can increase intracranial pressure, it may have beneficial effects on tissue oxygenation. We aimed to assess the effects of hypercapnia on brain tissue oxygenation (PbtO2). METHODS: This single-center retrospective study (November 2014 to June 2022) included all patients admitted to the intensive care unit after acute brain injury who required multimodal monitoring, including PbtO2 monitoring, and who underwent induced moderate hypoventilation and hypercapnia according to the decision of the treating physician. Patients with imminent brain death were excluded. Responders to hypercapnia were defined as those with an increase of at least 20% in PbtO2 values when compared to their baseline levels. RESULTS: On a total of 163 eligible patients, we identified 23 (14%) patients who underwent moderate hypoventilation (arterial partial pressure of carbon dioxide [PaCO2] from 44 [42-45] to 50 [49-53] mm Hg; p < 0.001) during the study period at a median of 6 (4-10) days following intensive care unit admission; six patients had traumatic brain injury, and 17 had subarachnoid hemorrhage. A significant overall increase in median PbtO2 values from baseline (21 [19-26] to 24 [22-26] mm Hg; p = 0.02) was observed. Eight (35%) patients were considered as responders, with a median increase of 7 (from 4 to 11) mm Hg of PbtO2, whereas nonresponders showed no changes (from - 1 to 2 mm Hg of PbtO2). Because of the small sample size, no variable independently associated with PbtO2 response was identified. No correlation between changes in PaCO2 and in PbtO2 was observed. CONCLUSIONS: In this study, a heterogeneous response of PbtO2 to induced hypercapnia was observed but without any deleterious elevations of intracranial pressure.

Serum-neuroproteins, near-infrared spectroscopy, and cognitive outcome after beach-chair shoulder surgery: Observational cohort study analyses.

BACKGROUND: Cerebral hypoxia may occur during surgery but currently used cerebral oxygenation saturation (rSO2) monitors remain controversial with respect to improving clinical outcome. Novel neuroprotein biomarkers are potentially released into systemic circulation and combined with near-infrared spectroscopy (NIRS) could clarify the presence of per-operative cerebral hypoxia. We investigated changes to serum-neuroprotein concentrations post-surgically, paired with NIRS and cognitive outcome, in patients operated in the beach chair position (BCP). METHODS: A prospective cohort in 28 shoulder surgery patients placed in the BCP. Blood samples were collected before induction of anaesthesia, and 2 hours and 3-5 days post-operatively. We analysed blood levels of biomarkers including tau and neurofilament light (NFL). We post hoc assessed the cross-wise relationship between biomarker levels and post-surgical changes in cognitive function and intraoperatively monitored rSO2 from NIRS. RESULTS: Serum-NFL decreased from 24.2 pg/mL to 21.5 (P = .02) 2 hours post-operatively, then increased to 27.7 pg/mL on day 3-5 (P = .03). Conversely, s-tau increased from 0.77 pg/mL to 0.98 (2 h), then decreased to 0.81 on day 3-5 (P = .08). In 14/28 patients, episodic rSO2 below 55% occurred, and the duration < 55% was correlated to change in s-tau (P < .05). The cognitive function z-score at 1 week and 3 mo. correlated to the change in tau (P = .01), but not to NFL. CONCLUSION: Some biomarkers were significantly changed with surgery in the beach chair position. The change was at some points associated to post-operative cognitive decline, and to intraoperative low rSO2. (237).

An increase in neutrophil-to-lymphocyte ratio predicts poor functional outcomes in older patients with acute ischemic stroke: a retrospective study.

The neutrophil-to-lymphocyte ratio has emerged as a predictor of functional outcome in stroke patients. However, less is known about the value of neutrophil to lymphocyte ratio in older patients. This clinical study evaluated whether the neutrophil-to-lymphocyte ratio is associated with stroke severity and early clinical outcomes in older patients with acute ischemic stroke. This observational study included acute ischemic stroke patients aged 80 years or older. The patients were divided into three groups, and information was collected, including demographic, clinical and laboratory data. The neutrophil associations to lymphocyte ratio with stroke severity and early clinical outcomes were assessed with logistic regression. Overall, 356 older patients were enrolled in this study, with a median age of 85.0 (82.0-88.0). Split by tertiles of neutrophil-to-lymphocyte ratio, 118 patients were in the bottom tertile (<2.17), 118 patients were in the middle tertile (2.17-3.36), and 120 patients were in the top tertile (>3.36). After multivariable analysis, patients in the highest tertile were likely to have moderate to severe stroke on admission (OR 4.87, 95% CI, 1.93-12.30, P = 0.001), higher risks of primary unfavorable outcome (OR 2.70, 95% CI, 1.09-6.69, P = 0.032) and secondary unfavorable outcome (OR 2.00, 95% CI, 1.00-4.00, P = 0.050) compared to the lowest tertile. Our finding demonstrated that the neutrophil-to-lymphocyte ratio is an independent predictor of stroke severity and early clinical outcomes in older patients with acute ischemic stroke.

Compression of a giant pseudomeningocele causing transient anoxic seizures-a case report.

Transient anoxic seizure upon application of pressure on a giant pseudomeningocele has never been reported in the literature; such abrupt changes in intracranial pressure due to large volume of cerebrospinal fluid (CSF) translocation, if left untreated may lead to permanent cerebral hypoxic injury and death. Here we describe a case of a 26-year-old woman who had undergone lumbar disc surgery in another unit few months ago and developed a large lump around her back. Any pressure on the lump resulted in headaches and at times episodes of seizures. Clinical examination revealed a very large fluid-filled lump consistent with a giant pseudomeningocele, confirmed by an MRI. A video EEG while applying pressure on the lump was recorded. The patient developed a typical seizure attack with a characteristic pattern of cerebral anoxia, and a paired ECG showed irregular rhythm with junctional and ventricular ectopic beats during the latter part of the attack, raising a suspicion of asystole. Upon relieving the pressure off the lump, the patient gradually regained consciousness with no permanent neurological deficit. We then discuss the pathophysiology of anoxic seizures and highlight the need to be vigilant in managing patients with such lesions in order to prevent permanent cerebral hypoxic injury and death.

AAV-Syn-BDNF-EGFP Virus Construct Exerts Neuroprotective Action on the Hippocampal Neural Network during Hypoxia In Vitro.

Brain-derived neurotrophic factor (BDNF) is one of the key signaling molecules that supports the viability of neural cells in various brain pathologies, and can be considered a potential therapeutic agent. However, several methodological difficulties, such as overcoming the blood⁻brain barrier and the short half-life period, challenge the potential use of BDNF in clinical practice. Gene therapy could overcome these limitations. Investigating the influence of viral vectors on the neural network level is of particular interest because viral overexpression affects different aspects of cell metabolism and interactions between neurons. The present work aimed to investigate the influence of the adeno-associated virus (AAV)-Syn-BDNF-EGFP virus construct on neural network activity parameters in an acute hypobaric hypoxia model in vitro. MATERIALS AND METHODS: An adeno-associated virus vector carrying the BDNF gene was constructed using the following plasmids: AAV-Syn-EGFP, pDP5, DJvector, and pHelper. The developed virus vector was then tested on primary hippocampal cultures obtained from C57BL/6 mouse embryos (E18). Acute hypobaric hypoxia was induced on day 21 in vitro. Spontaneous bioelectrical and calcium activity of neural networks in primary cultures and viability tests were analysed during normoxia and during the posthypoxic period. RESULTS: BDNF overexpression by AAV-Syn-BDNF-EGFP does not affect cell viability or the main parameters of spontaneous bioelectrical activity in normoxia. Application of the developed virus construct partially eliminates the negative hypoxic consequences by preserving cell viability and maintaining spontaneous bioelectrical activity in the cultures. Moreover, the internal functional structure, including the activation pattern of network bursts, the number of hubs, and the number of connections within network elements, is also partially preserved. BDNF overexpression prevents a decrease in the number of cells exhibiting calcium activity and maintains the frequency of calcium oscillations. CONCLUSION: This study revealed the pronounced antihypoxic and neuroprotective effects of AAV-Syn-BDNF-EGFP virus transduction in an acute normobaric hypoxia model.

Cerebral desaturation events in the beach chair position: correlation of noninvasive blood pressure and estimated temporal mean arterial pressure.

BACKGROUND: Cerebral oximetry (rSO2) has emerged as an important tool for monitoring of cerebral perfusion during surgery. High rates of cerebral desaturation events (CDEs) have been reported during surgery in the beach chair position. However, correlations have not been made with blood pressure measured at the cerebral level. The purpose of this study was to examine the correlations between brachial noninvasive blood pressure (NIBP) and estimated temporal mean arterial pressure (eTMAP) during CDEs in the beach chair position. METHODS: Fifty-seven patients underwent elective shoulder surgery in the beach chair position. Values for eTMAP, NIBP, and rSO2 were recorded supine (0°) after induction and when a CDE occurred in the 70° beach chair position. Twenty-six patients experienced 45 CDEs, defined as a 20% drop in rSO2 from baseline. RESULTS: Median reduction in NIBP, eTMAP, and rSO2 from baseline to the CDE were 48.2%, 75.5%, and 33.3%, respectively. At baseline, there was a significant weak negative correlation between rSO2 and NIBP (rs = -0.300; P = .045) and no significant association between rSO2 and eTMAP (rs = -0.202; P = .183). During CDEs, there were no significant correlations between rSO2 and NIBP (rs = -0.240; P = .112) or between rSO2 and eTMAP (rs = -0.190; P = .212). No significant correlation between the decrease in rSO2 and NIBP (rs = 0.064; P = .675) or between rSO2 and eTMAP (rs = 0.121; P = .430) from baseline to CDE was found. CONCLUSION: NIBP and eTMAP are unreliable methods for identifying a CDE in the beach chair position. Cerebral oximetry provides additional information to the values obtained from NIBP and eTMAP, and all should be considered independently and collectively.

Altered astrocyte-neuronal interactions after hypoxia-ischemia in the neonatal brain in female and male rats.

BACKGROUND AND PURPOSE: Increased susceptibility to excitotoxicity of the neonatal brain after hypoxia-ischemia (HI) may be caused by limited capacity of astrocytes for glutamate uptake, and mitochondrial failure probably plays a key role in the delayed injury cascade. Male infants have poorer outcome than females after HI, possibly linked to differential intermediary metabolism. METHODS: [1-(13)C]glucose and [1,2-(13)C]acetate were injected at zero, 6, and 48 hours after unilateral HI in 7-day-old rats. Intermediary metabolism was analyzed with magnetic resonance spectroscopy. RESULTS: Mitochondrial metabolism was generally reduced in the ipsilateral hemisphere for ≤6 hours after HI, whereas contralaterally, it was reduced in neurons but not in astrocytes. Transfer of glutamate from neurons to astrocytes was increased in the contralateral, but not in the ipsilateral hemisphere at 0 hour, and reduced bilaterally at 6 hours after HI. The transfer of glutamine from astrocytes to glutamatergic neurons was unaltered in both hemispheres, whereas the transfer of glutamine to GABAergic neurons was increased ipsilaterally at 0 hour. Anaplerosis (astrocytes) was decreased, whereas partial pyruvate recycling (astrocytes) was increased directly after HI. Male pups had lower astrocytic mitochondrial metabolism than females immediately after HI, whereas that of females was reduced longer and encompassed both neurons and astrocytes. CONCLUSIONS: The prolonged depression in mitochondrial metabolism indicates that mitochondria are vulnerable targets in the delayed injury after neonatal HI. The degree of astrocytic malfunction may be a valid indicator of outcome after hypoxic/HI brain injury and may be linked to the differential outcome in males and females.

[Multimodal neuromonitoring in traumatic brain injury: contribution of PTiO2]. / Neuromonitorización multimodal en el TCE: aportación de la PTiO2.

The main goal of exhaustively monitoring neurocritical patients is to avoid secondary injury. In the last few years we have witnessed an increase in brain monitoring tools, beyond the checking of intracranial and brain perfusion pressures. These widely used systems offer valuable but possibly insufficient information. Awareness and correction of brain hypoxia is a useful and interesting measure, not only for diagnostic purposes but also when deciding treatment, and to predict an outcome. In this context, it would be of great interest to use all the information gathered from brain oxygenation monitoring systems in conjunction with other available multimodal monitoring devices, in order to offer individualized treatment for each patient.

The neuroprotective effects of normobaric oxygen therapy after stroke.

BACKGROUND: Stroke, including ischemic and hemorrhagic stroke, is a severe and prevalent acute cerebrovascular disease. The development of hypoxia following stroke can trigger a cascade of pathological events, including mitochondrial dysfunction, energy deficiency, oxidative stress, neuroinflammation, and excitotoxicity, all of which are often associated with unfavorable prognosis. Nonetheless, a noninvasive intervention, referred to as normobaric hyperoxia (NBO), is known to have neuroprotective effects against stroke. RESULTS: NBO can exert neuroprotective effects through various mechanisms, such as the rescue of hypoxic tissues, preservation of the blood-brain barrier, reduction of brain edema, alleviation of neuroinflammation, improvement of mitochondrial function, mitigation of oxidative stress, reduction of excitotoxicity, and inhibition of apoptosis. These mechanisms may help improve the prognosis of stroke patients. CONCLUSIONS: This review summarizes the mechanism by which hypoxia causes brain injury and how NBO can act as a neuroprotective therapy to treat stroke. We conclude that NBO has significant potential for treating stroke and may represent a novel therapeutic strategy.

The Effect of Propofol on the Hippocampus in Chronic Cerebral Hypoxia in a Rat Model Through Klotho Regulation.

BACKGROUND/AIM: Chronic cerebral hypoxia often leads to brain damage and inflammation. Propofol is suggested to have neuroprotective effects under anaesthesia. MATERIALS AND METHODS: This study used rat models with carotid artery coarctation or closure. Four groups of rats were compared: a control group, a propofol-treated group, a group with bilateral common carotid artery blockage (BCAO), and a BCAO group treated with propofol post-surgery. RESULTS: The Morris water maze test indicated cognitive impairment in BCAO rats, which also showed hippocampal structure changes, oxidative stress markers alteration, and reduced Klotho expression. Propofol treatment post-BCAO surgery improved these outcomes, suggesting its potential in mitigating chronic cerebral hypoxia effects. CONCLUSION: Propofol may increase klotho levels and reduce apoptosis and inflammation linked to oxidative stress in cognitively impaired mice.

Sevoflurane postconditioning ameliorates cerebral hypoxia/reoxygenation injury in zebrafish involving the Akt/GSK-3ß pathway activation and the microtubule-associated protein 2 promotion.

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-3ß pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3ß 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-3ß, p-GSK-3ß, 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-3ß/GSK-3ß. 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-3ß pathway and promotion of MAP2 expression.

Innovative in vivo rat model for global cerebral hypoxia: a new approach to investigate therapeutic and preventive drugs.

Introduction: Severe acute global cerebral hypoxia can lead to significant disability in humans. Although different animal models have been described to study hypoxia, there is no endogenous model that considers hypoxia and its effect on the brain as an independent factor. Thus, we developed a minimally invasive rat model, which is based on the non-depolarizing muscle blocking agent rocuronium in anesthetized animals. This drug causes respiratory insufficiency by paralysis of the striated muscles. Methods: In this study, 14 rats underwent 12 min of hypoxemia with an oxygen saturation of approximately 60% measured by pulse oximetry; thereafter, animals obtained sugammadex to antagonize rocuronium immediately. Results: Compared to controls (14 rats, anesthesia only), hypoxic animals demonstrated significant morphological alterations in the hippocampus (cell decrease in the CA 1 region) and the cerebellum (Purkinje cell decrease), as well as significant changes in hypoxia markers in blood (Hif2α, Il1ß, Tgf1ß, Tnfα, S100b, cspg2, neuron-specific enolase), hippocampus (Il1ß, Tnfα, S100b, cspg2, NSE), and cerebellum (Hif1α, Tnfα, S100b, cspg2, NSE). Effects were more pronounced in females than in males. Discussion: Consequently, this model is suitable to induce hypoxemia with consecutive global cerebral hypoxia. As significant morphological and biochemical changes were proven, it can be used to investigate therapeutic and preventive drugs for global cerebral hypoxia.

Effects to cerebral oxygenation by arteriovenous fistula creation in patients with chronic kidney disease.

BACKGROUND: Vascular access, including arteriovenous fistula (AVF), is essential in patients undergoing hemodialysis (HD). However, the presence of AVF is non-physiological in humans and could pose a burden to the systemic circulation or tissue microcirculation, potentially affecting tissue oxygenation, including in the brain. Recently, near-infrared spectroscopy has been used to measure regional oxygen saturation (rSO2) as a marker of cerebral oxygenation in various settings, including in patients undergoing HD. Thus far, no studies have reported changes in cerebral rSO2 before and after AVF creation. This study aimed to monitor the differences in cerebral oxygenation before and after AVF creation and to clarify the clinical factors affecting the changes in cerebral rSO2. METHODS: Forty-eight patients (34 men, 14 women) with chronic kidney disease (CKD) who were not undergoing dialysis and newly created AVF were recruited. Cerebral rSO2 values before and after AVF creation were evaluated using near-infrared spectroscopy (INVOS 5100c). RESULTS: Cerebral rSO2 values were significantly changed from 60.3% ± 7.5% to 58.4% ± 6.8% before and after AVF creation in all patients (p < 0.001). Cerebral rSO2 were also lower in patients with diabetes mellitus (DM) than in those without DM (57.5 ± 7.1 vs 63.7 ± 6.5, p = 0.003) before surgery; however, no differences of changes in cerebral rSO2 were observed between the two groups after AVF creation. Additionally, multivariate regression analysis identified changes in HR (standardized coefficient: 0.436) as independent factors associated with changes in cerebral rSO2. CONCLUSION: Surgically created AVF was associated with the deterioration of cerebral rSO2 in patients with CKD not undergoing dialysis. Notably, AVF could cause cerebral hypoxia, and thus further studies are needed to clarify the clinical factors influencing changes in cerebral oxygenation after AVF creation.

Transcriptional Responses of Different Brain Cell Types to Oxygen Decline.

Brain hypoxia is associated with a wide range of physiological and clinical conditions. Although oxygen is an essential constituent of maintaining brain functions, our understanding of how specific brain cell types globally respond and adapt to decreasing oxygen conditions is incomplete. In this study, we exposed mouse primary neurons, astrocytes, and microglia to normoxia and two hypoxic conditions and obtained genome-wide transcriptional profiles of the treated cells. Analysis of differentially expressed genes under conditions of reduced oxygen revealed a canonical hypoxic response shared among different brain cell types. In addition, we observed a higher sensitivity of neurons to oxygen decline, and dissected cell type-specific biological processes affected by hypoxia. Importantly, this study establishes novel gene modules associated with brain cells responding to oxygen deprivation and reveals a state of profound stress incurred by hypoxia.

Lance-Adams Syndrome in the Intensive Care Unit: A Case Report.

Lance-Adams syndrome (LAS), or chronic post-hypoxic myoclonus, is a myoclonic disorder following acute cerebral hypoxia after successful cardiopulmonary resuscitation (CPR). LAS is distinct from acute post-hypoxic myoclonus (acute PHM), presenting with myoclonic jerks and cerebellar ataxia after regaining consciousness. However, the overlap at the onset complicates differentiation and may lead to the withdrawal of life-sustaining measures, especially in sedated ICU patients. The presented case involves a 77-year-old male diagnosed with LAS post-CPR. Despite the presence of early myoclonic jerks EEG, laboratory testing, and neuroimaging showed no definitive proof of irreversible neurological damage. Once diagnosed, treatment involved sequential antiseizure medications and physical therapy when the patient achieved full consciousness. However, the patient ultimately faced severe disabilities and was unable to recover. This case report emphasizes the importance of limiting sedation, comprehensive clinical examination, and the use of complementary tests when no definitive proof of irreversible neurological damage is present after acute cerebral hypoxia. While LAS has a better vital prognosis than acute PHM, it is associated with poor neurofunctional recovery and chronic disability in most cases. Further research is essential for evidence-based management.

Cerebrospinal Fluid Dynamics and Partial Pressure of Carbon Dioxide as Prognostic Indicators in Hypoxic-Ischemic Brain Injury Following Cardiac Arrest.

Changes in cerebrospinal fluid (CSF) dynamics can have adverse effects on neuronal function. We hypothesized that patients with hypoxic-ischemic brain injury (HIBI) showing poor neurological outcomes after cardiac arrest (CA) would exhibit changes in CSF dynamics, leading to abnormalities in gas diffusion within the CSF. Therefore, we investigated the prognostic value of the CSF partial pressure of carbon dioxide (PcsfCO2) in CA survivors who underwent targeted temperature management (TTM). We retrospectively analyzed the 6-month neurological outcomes, CSF, and arterial blood gas parameters of 67 CA survivors. Patients were divided into good and poor neurological outcome groups, and the predictive value of PcsfCO2 for poor neurological outcomes was assessed using receiver operating characteristic curve analysis. Among all patients, 39 (58.2%) had poor neurological outcomes. Significant differences in PcsfCO2 levels between the groups were observed, with lower PcsfCO2 levels on Day 1 showing the highest predictive value at a cutoff of 30 mmHg (area under the curve, sensitivity, and specificity were 0.823, 77.8%, and 79.0%, respectively). These results suggest that PcsfCO2 might serve not only as a unique marker for the severity of hypoxic-ischemic brain injury (HIBI), independent of extracorporeal CO2 levels, but also as an objective indicator of changes in CSF dynamics. This study highlights the potential prognostic and diagnostic utility of PcsfCO2 during TTM in CA survivors, emphasizing its importance in evaluating CSF dynamics and neurological recovery post CA. However, larger multicenter studies are warranted to address potential limitations associated with sample size and outcome assessment methods.