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Neurocritical Care Jun 2020Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding...
BACKGROUND
Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety.
METHODS
The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy.
RESULTS
The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy.
CONCLUSION
The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.
Topics: Brain Edema; Brain Injuries, Traumatic; Cerebral Hemorrhage; Cerebrospinal Fluid Shunts; Critical Care; Diuretics, Osmotic; Emergency Medical Services; Glucocorticoids; Hepatic Encephalopathy; Humans; Intracranial Hypertension; Ischemic Stroke; Mannitol; Meningitis, Bacterial; Patient Positioning; Saline Solution, Hypertonic; Societies, Medical; Subarachnoid Hemorrhage
PubMed: 32227294
DOI: 10.1007/s12028-020-00959-7 -
Neuropharmacology Feb 2019Cerebral edema (CE) and resultant intracranial hypertension are associated with unfavorable prognosis in traumatic brain injury (TBI). CE is a leading cause of... (Review)
Review
Cerebral edema (CE) and resultant intracranial hypertension are associated with unfavorable prognosis in traumatic brain injury (TBI). CE is a leading cause of in-hospital mortality, occurring in >60% of patients with mass lesions, and ∼15% of those with normal initial computed tomography scans. After treatment of mass lesions in severe TBI, an important focus of acute neurocritical care is evaluating and managing the secondary injury process of CE and resultant intracranial hypertension. This review focuses on a contemporary understanding of various pathophysiologic pathways contributing to CE, with a subsequent description of potential targeted therapies. There is a discussion of identified cellular/cytotoxic contributors to CE, as well as mechanisms that influence blood-brain-barrier (BBB) disruption/vasogenic edema, with the caveat that this distinction may be somewhat artificial since molecular processes contributing to these pathways are interrelated. While an exhaustive discussion of all pathways with putative contributions to CE is beyond the scope of this review, the roles of some key contributors are highlighted, and references are provided for further details. Potential future molecular targets for treating CE are presented based on pathophysiologic mechanisms. We thus aim to provide a translational synopsis of present and future strategies targeting CE after TBI in the context of a paradigm shift towards precision medicine. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".
Topics: Animals; Brain Edema; Brain Injuries, Traumatic; Humans; Neuroprotective Agents
PubMed: 30086289
DOI: 10.1016/j.neuropharm.2018.08.004 -
European Respiratory Review : An... Jan 2017At any point 1-5 days following ascent to altitudes ≥2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain... (Review)
Review
At any point 1-5 days following ascent to altitudes ≥2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly. This review provides detailed information about each of these important clinical entities. After reviewing the clinical features, epidemiology and current understanding of the pathophysiology of each disorder, we describe the current pharmacological and nonpharmacological approaches to the prevention and treatment of these diseases.
Topics: Acute Disease; Adult; Aged; Altitude; Altitude Sickness; Animals; Brain Edema; Cerebral Arteries; Cerebrovascular Circulation; Female; Humans; Hypertension, Pulmonary; Hypoxia; Inflammation; Male; Middle Aged; Prognosis; Pulmonary Circulation; Risk Factors; Time Factors; Vasoconstriction
PubMed: 28143879
DOI: 10.1183/16000617.0096-2016 -
Journal of Cerebral Blood Flow and... Mar 2016Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of... (Review)
Review
Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema.
Topics: Animals; Aquaporins; Blood-Brain Barrier; Brain; Brain Edema; Humans; Ion Transport; Ions; Permeability; Water
PubMed: 26661240
DOI: 10.1177/0271678X15617172 -
Neurotherapeutics : the Journal of the... Oct 2019Cerebral edema is commonly associated with cerebral pathology, and the clinical manifestation is largely related to the underlying lesioned tissue. Brain edema usually... (Review)
Review
Cerebral edema is commonly associated with cerebral pathology, and the clinical manifestation is largely related to the underlying lesioned tissue. Brain edema usually amplifies the dysfunction of the lesioned tissue and the burden of cerebral edema correlates with increased morbidity and mortality across diseases. Our modern-day approach to the medical management of cerebral edema has largely revolved around, an increasingly artificial distinction between cytotoxic and vasogenic cerebral edema. These nontargeted interventions such as hyperosmolar agents and sedation have been the mainstay in clinical practice and offer noneloquent solutions to a dire problem. Our current understanding of the underlying molecular mechanisms driving cerebral edema is becoming much more advanced, with differences being identified across diseases and populations. As our understanding of the underlying molecular mechanisms in neuronal injury continues to expand, so too is the list of targeted therapies in the pipeline. Here we present a brief review of the molecular mechanisms driving cerebral edema and a current overview of our understanding of the molecular targets being investigated.
Topics: Animals; Blood-Brain Barrier; Brain Edema; Clinical Trials as Topic; Disease Management; Forecasting; Humans; Membrane Transport Proteins; PPAR gamma; Saline Solution, Hypertonic
PubMed: 31512062
DOI: 10.1007/s13311-019-00779-4 -
Neurobiology of Disease Jan 2023Intracerebral hemorrhage (ICH) accounts for about 10% of all strokes in the United States of America causing a high degree of disability and mortality. There is initial... (Review)
Review
Intracerebral hemorrhage (ICH) accounts for about 10% of all strokes in the United States of America causing a high degree of disability and mortality. There is initial (primary) brain injury due to the mechanical disruption caused by the hematoma. There is then secondary injury, triggered by the initial injury but also the release of various clot-derived factors (e.g., thrombin and hemoglobin). ICH alters brain fluid homeostasis. Apart from the initial hematoma mass, ICH causes blood-brain barrier disruption and parenchymal cell swelling, which result in brain edema and intracranial hypertension affecting patient prognosis. Reducing brain edema is a critical part of post-ICH care. However, there are limited effective treatment methods for reducing perihematomal cerebral edema and intracranial pressure in ICH. This review discusses the mechanisms underlying perihematomal brain edema formation, the effects of sex and age, as well as how edema is resolved. It examines progress in pharmacotherapy, particularly focusing on drugs which have been or are currently being investigated in clinical trials.
Topics: Humans; Brain Edema; Cerebral Hemorrhage; Brain; Treatment Outcome; Hematoma
PubMed: 36481437
DOI: 10.1016/j.nbd.2022.105948 -
Journal of Molecular Cell Biology Sep 2022High-altitude cerebral edema (HACE) is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude. The formation...
High-altitude cerebral edema (HACE) is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude. The formation of HACE is affected by both vasogenic and cytotoxic edema. The over-activated microglia potentiate the damage of blood-brain barrier (BBB) and exacerbate cytotoxic edema. In light with the activation of microglia in HACE, we aimed to investigate whether the over-activated microglia were the key turning point of acute mountain sickness to HACE. In in vivo experiments, by exposing mice to hypobaric hypoxia (7000 m above sea level) to induce HACE model, we found that microglia were activated and migrated to blood vessels. Microglia depletion by PLX5622 obviously relieved brain edema. In in vitro experiments, we found that hypoxia induced cultured microglial activation, leading to the destruction of endothelial tight junction and astrocyte swelling. Up-regulated nuclear respiratory factor 1 (NRF1) accelerated pro-inflammatory factors through transcriptional regulation on nuclear factor kappa B p65 (NF-κB p65) and mitochondrial transcription factor A (TFAM) in activated microglia under hypoxia. NRF1 also up-regulated phagocytosis by transcriptional regulation on caveolin-1 (CAV-1) and adaptor-related protein complex 2 subunit beta (AP2B1). The present study reveals a new mechanism in HACE: hypoxia over-activates microglia through up-regulation of NRF1, which both induces inflammatory response through transcriptionally activating NF-κB p65 and TFAM, and enhances phagocytic function through up-regulation of CAV-1 and AP2B1; hypoxia-activated microglia destroy the integrity of BBB and release pro-inflammatory factors that eventually induce HACE.
Topics: Adaptor Protein Complex 2; Altitude; Altitude Sickness; Animals; Brain Edema; Caveolin 1; Hypoxia; Mice; Microglia; NF-kappa B; Nuclear Respiratory Factor 1
PubMed: 35704676
DOI: 10.1093/jmcb/mjac036 -
Frontiers in Immunology 2021Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma,... (Review)
Review
Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma, and developing targeted therapy against secondary brain injury (SBI) after ICH is equally essential. Numerous preclinical and clinical studies have demonstrated that perihematomal edema (PHE) is a quantifiable marker of SBI after ICH and is associated with a poor prognosis. Thus, PHE has been considered a promising therapeutic target for ICH. However, the findings derived from existing studies on PHE are disparate and unclear. Therefore, it is necessary to classify, compare, and summarize the existing studies on PHE. In this review, we describe the growth characteristics and relevant underlying mechanism of PHE, analyze the contributions of different risk factors to PHE, present the potential impact of PHE on patient outcomes, and discuss the currently available therapeutic strategies.
Topics: Brain; Brain Edema; Cerebral Hemorrhage; Glyburide; Hematoma; Humans; Hypoglycemic Agents; Magnetic Resonance Imaging; Neurogenic Inflammation; Risk Factors
PubMed: 34737745
DOI: 10.3389/fimmu.2021.740632 -
Archivos Argentinos de Pediatria Oct 2020Cerebral edema (CE) is the most severe complication of diabetic ketoacidosis (DKA) in children. There is no accurate knowledge of CE pathogenesis and its onset has been...
INTRODUCTION
Cerebral edema (CE) is the most severe complication of diabetic ketoacidosis (DKA) in children. There is no accurate knowledge of CE pathogenesis and its onset has been related to intravenous rehydration therapy during the initial treatment.
OBJECTIVES
To estimate the prevalence of CE among DKA patients treated at Hospital General de Niños Pedro de Elizalde with intravenous rehydration and analyze potential risk factors for the development of CE.
MATERIALS AND METHODS
Cross-sectional prevalence study and exploratory analysis to compare clinical and laboratory characteristics between patients with and without CE. Patients aged 1-18 years hospitalized with the diagnosis of DKA between January 1st, 2005 and December 31st, 2014 were included.
RESULTS
A total of 693 DKA events from 561 medical records were analyzed. Ten patients had evidence of CE (1.44 %; 95 % confidence interval: 0.8-2.6). Patients with CE had higher serum urea levels (p < 0.001), lower carbon dioxide pressure (p < 0.001), and lower serum sodium levels (p < 0.001) than those without CE.
CONCLUSION
The prevalence of CE among DKA patients was 1.44 %, smaller than that reported in our country (1.8 %). The risk factors at admission associated with CE development were high serum urea levels, hyponatremia, and hypocapnia.
Topics: Adolescent; Argentina; Brain Edema; Child; Child, Preschool; Cross-Sectional Studies; Diabetic Ketoacidosis; Female; Fluid Therapy; Humans; Hypocapnia; Hyponatremia; Infant; Male; Prevalence; Risk Factors; Urea
PubMed: 32924396
DOI: 10.5546/aap.2020.eng.332 -
Cell Communication and Signaling : CCS Oct 2022High-altitude cerebral edema (HACE) is a serious and potentially fatal brain injury that is caused by acute hypobaric hypoxia (HH) exposure. Vasogenic edema is the main...
BACKGROUND
High-altitude cerebral edema (HACE) is a serious and potentially fatal brain injury that is caused by acute hypobaric hypoxia (HH) exposure. Vasogenic edema is the main pathological factor of this condition. Hypoxia-induced disruptions of tight junctions in the endothelium trigger blood‒brain barrier (BBB) damage and induce vasogenic edema. Nuclear respiratory factor 1 (NRF1) acts as a major regulator of hypoxia-induced endothelial cell injury, and caveolin-1 (CAV-1) is upregulated as its downstream gene in hypoxic endothelial cells. This study aimed to investigate whether CAV-1 is involved in HACE progression and the underlying mechanism.
METHODS
C57BL/6 mice were exposed to HH (7600 m above sea level) for 24 h, and BBB injury was assessed by brain water content, Evans blue staining and FITC-dextran leakage. Immunofluorescence, transmission electron microscope, transendothelial electrical resistance (TEER), transcytosis assays, and western blotting were performed to confirm the role and underlying mechanism of CAV-1 in the disruption of tight junctions and BBB permeability. Mice or bEnd.3 cells were pretreated with MβCD, a specific blocker of CAV-1, and the effect of CAV-1 on claudin-5 internalization under hypoxic conditions was detected by immunofluorescence, western blotting, and TEER. The expression of NRF1 was knocked down, and the regulation of CAV-1 by NRF1 under hypoxic conditions was examined by qPCR, western blotting, and immunofluorescence.
RESULTS
The BBB was severely damaged and was accompanied by a significant loss of vascular tight junction proteins in HACE mice. CAV-1 was significantly upregulated in endothelial cells, and claudin-5 explicitly colocalized with CAV-1. During the in vitro experiments, hypoxia increased cell permeability, CAV-1 expression, and claudin-5 internalization and downregulated tight junction proteins. Simultaneously, hypoxia induced the upregulation of CAV-1 by activating NRF1. Blocking CAV-1-mediated intracellular transport improved the integrity of TJs in hypoxic endothelial cells and effectively inhibited the increase in BBB permeability and brain water content in HH animals.
CONCLUSIONS
Hypoxia upregulated CAV-1 transcription via the activation of NRF1 in endothelial cells, thus inducing the internalization and autophagic degradation of claudin-5. These effects lead to the destruction of the BBB and trigger HACE. Therefore, CAV-1 may be a potential therapeutic target for HACE. Video abstract.
Topics: Animals; Mice; Altitude; Blood-Brain Barrier; Brain Edema; Caveolin 1; Claudin-5; Endothelial Cells; Hypoxia; Mice, Inbred C57BL; Nuclear Respiratory Factor 1; Tight Junction Proteins; Tight Junctions
PubMed: 36253854
DOI: 10.1186/s12964-022-00976-3