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Cerebral Edema (CE) is the final common pathway of brain death. In severe neurological disease, neuronal cell damage first contributes to tissue edema, and then Increased Intracranial Pressure (ICP) occurs, which results in diminishing cerebral perfusion pressure. In turn, anoxic brain injury brought on by decreased cerebral perfusion pressure eventually results in neuronal cell impairment, creating a vicious cycle. Traditionally, CE is understood to be tightly linked to elevated ICP, which ultimately generates cerebral hernia and is therefore regarded as a risk factor for mortality. Intracranial hypertension and brain edema are two serious neurological disorders that are commonly treated with mannitol. However, mannitol usage should be monitored since inappropriate utilization of the substance could conversely have negative effects on CE patients. CE is thought to be related to bloodbrain barrier dysfunction. Nonetheless, a fluid clearance mechanism called the glial-lymphatic or glymphatic system was updated. This pathway facilitates the transport of cerebrospinal fluid (CSF) into the brain along arterial perivascular spaces and later into the brain interstitium. After removing solutes from the neuropil into meningeal and cervical lymphatic drainage arteries, the route then directs flows into the venous perivascular and perineuronal regions. Remarkably, the dual function of the glymphatic system was observed to protect the brain from further exacerbated damage. From our point of view, future studies ought to concentrate on the management of CE based on numerous targets of the updated glymphatic system. Further clinical trials are encouraged to apply these agents to the clinic as soon as possible.

The management of acute liver failure (ALF) in modern hepatology intensive care units (ICU) has improved patient outcomes. Critical care management of hepatic encephalopathy, cerebral edema, fluid and electrolytes; prevention of infections and organ support are central to improved outcomes of ALF. In particular, the pathogenesis of encephalopathy is multifactorial, with ammonia, elevated intra-cranial pressure and systemic inflammation playing a central role. Although ALF remains associated with high mortality, the availability of supportive care, including organ failure support such as plasma exchange, timely mechanical ventilation or continuous renal replacement therapy, either conservatively manages patients with ALF or offers bridging therapy until liver transplantation. Thus, appropriate critical care management has improved the likelihood of patient recovery in ALF. ICU care interventions such as monitoring of cerebral edema, fluid status assessment and interventions for sepsis prevention, nutritional support and management of electrolytes can salvage a substantial proportion of patients. In this review, we discuss the key aspects of critical care management of ALF., (© 2024. Indian Society of Gastroenterology.)

Purpose of Review: The diagnosis of brain tumors often leads to complications that are either related to the tumor itself or the tumor-directed and supportive therapies, increasing the burden on the patients' quality of life and even survival. This article reviews the medical and neurological conditions that commonly complicate the disease course of brain tumors patients., Recent Findings: Various mechanisms have been newly identified to be involved in the pathophysiology of seizures and brain edema and can help advance the treatment of such complications. There have also been new developments in the management of thromboembolic disease and cognitive impairment. Medical and neurological complications are being identified more often in brain tumor patients with the improved survival provided by therapeutic advances. Early and proper identification and management of such complications are crucial for a better survival and quality of life., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Elevated intracranial pressure due to cerebral edema is associated with very poor survival in patients with acute liver failure (ALF). Placing an intracranial pressure monitor (ICPm) aids in management of intracranial hypertension, but is associated with potentially fatal hemorrhagic complications related to the severe coagulopathy associated with ALF., Methods: An institutional Acute Liver Failure Clinical Protocol (ALF-CP) was created to correct ALF coagulopathy prior to placing parenchymal ICP monitoring bolts. We aimed to investigate the frequency, severity, and clinical significance of hemorrhagic complications associated with ICPm bolt placement in the setting of an ALF-CP. All assessed patients were managed with the ALF-CP and had rigorous radiologic follow-up allowing assessment of the occurrence and chronology of hemorrhagic complications. We also aimed to compare our outcomes to other studies that were identified through a comprehensive review of the literature., Results: Fourteen ALF patients were included in our analysis. There was no symptomatic hemorrhage after ICP monitor placement though four patients were found to have minor intraparenchymal asymptomatic hemorrhages after liver transplant when the ICP monitor had been removed, making the rate of radiographically identified clinically asymptomatic hemorrhage 28.6%. These results compare favorably to those found in a comprehensive review of the literature which revealed rates as high as 17.5% for symptomatic hemorrhages and 30.4% for asymptomatic hemorrhage., Conclusion: This study suggests that an intraparenchymal ICPm can be placed safely in tertiary referral centers which utilize a protocol such as the ALF-CP that aggressively corrects coagulopathy. The ALF-CP led to advantageous outcomes for ICPm placement with a 0% rate of symptomatic and low rate of asymptomatic hemorrhagic complications, which compares well to results reported in other series. A strict ICPm placement protocol in this setting facilitates management of ALF patients with cerebral edema during the wait time to transplantation or spontaneous recovery., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Patients with liver disease often have alteration of neurological status which requires admission to an intensive care unit. Patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and rarely cirrhosis are at risk of cerebral edema. These patients require prompt assessment of neurological status including assessment of intra-cranial pressure (ICP) and monitoring metabolic parameters like arterial/venous ammonia levels, serum creatinine and serum electrolytes so that timely specific therapy for raised ICP can be instituted to prevent permanent neurological dysfunction. The overall aims of neuromonitoring and sedation protocols in a liver intensive care unit are to identify the level of multifactorial metabolic encephalopathy, individualize sedation and analgesia requirements for patients on mechanical ventilation, institute specific therapy to correct the neurological insult in ALF and ACLF, provide clear physiological data for guided therapy of drugs like muscle relaxants, antiepileptics, and cerebral edema reducing agents, and assist with overall prognostication. In this review article we will outline the clinical scenarios related to liver disease requiring intensive care and neuromonitoring, current techniques of neurological assessment, sedation protocols and point of care tests which enable the treating physician and intensivist guide therapy for raised ICP., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-min blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Objective: Intracerebral hemorrhage is one of the diseases with the highest mortality and poorest prognosis worldwide. Spontaneous intracerebral hemorrhage (SICH) typically presents acutely, prompt and expedited radiological examination is crucial for diagnosis, localization, and quantification of the hemorrhage. Early detection and accurate segmentation of perihematomal edema (PHE) play a critical role in guiding appropriate clinical intervention and enhancing patient prognosis. However, the progress and assessment of computer-aided diagnostic methods for PHE segmentation and detection face challenges due to the scarcity of publicly accessible brain CT image datasets., Methods: This study establishes a publicly available CT dataset named PHE-SICH-CT-IDS for perihematomal edema in spontaneous intracerebral hemorrhage. The dataset comprises 120 brain CT scans and 7,022 CT images, along with corresponding medical information of the patients. To demonstrate its effectiveness, classical algorithms for semantic segmentation, object detection, and radiomic feature extraction are evaluated. The experimental results confirm the suitability of PHE-SICH-CT-IDS for assessing the performance of segmentation, detection and radiomic feature extraction methods., Results: This study conducts numerous experiments using classical machine learning and deep learning methods, demonstrating the differences in various segmentation and detection methods on the PHE-SICH-CT-IDS. The highest precision achieved in semantic segmentation is 76.31%, while object detection attains a maximum precision of 97.62%. The experimental results on radiomic feature extraction and analysis prove the suitability of PHE-SICH-CT-IDS for evaluating image features and highlight the predictive value of these features for the prognosis of SICH patients., Conclusion: To the best of our knowledge, this is the first publicly available dataset for PHE in SICH, comprising various data formats suitable for applications across diverse medical scenarios. We believe that PHE-SICH-CT-IDS will allure researchers to explore novel algorithms, providing valuable support for clinicians and patients in the clinical setting. PHE-SICH-CT-IDS is freely published for non-commercial purpose at https://figshare.com/articles/dataset/PHE-SICH-CT-IDS/23957937., Competing Interests: Declaration of competing interest We state that there is no Conflict of Interest in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: Cinnamaldehyde (CA), the main active constituent of cinnamon oil, is reported to have neuroprotective effects. However, the potential benefits of CA for brain protection in hepatic encephalopathy (HE) are still not understood. Thus, the present study investigates the possible ameliorative effect of CA (70 mg/kg/day, I.P.) either alone or in combination with lactulose (Lac) (5.3 g/kg/day, oral) against thioacetamide (TAA)-induced hepatic encephalopathy in rats., Materials and Methods: For induction of HE, TAA (200 mg/kg) was intraperitoneally administered for 1 week at alternative days. CA, Lac and Lac+CA were administered for 14 days prior to and for further 7 days together with TAA injection., Key Findings: CA, Lac and Lac+CA combination effectively attenuated TAA-induced HE; as indicated by the improvement in behavioral tests, mitigation of pathological abnormalities in both liver and brain, the significant reduction in serum hyperammonemia and amelioration in liver function biomarkers; ALT and AST. This was accompanied with a substantial restoration of redox state in liver and brain; MDA and GSH levels. Moreover, CA, Lac and Lac+CA combination reduced neuroinflammation as demonstrated by the notable attenuation of P2X7R, NLRP3, caspase-1, IL-1β, GFAP and Iba1 brain levels, as well as the amelioration of brain edema as manifested by reduction in AQP4 levels in brain., Significance: Our study has demonstrated that CA in combination with Lac possesses a superior neuroprotective effect over Lac alone against TAA-induced HE by attenuation of P2X7R/NLRP3 mediated neuroinflammation and relieving brain edema., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: It has been reported activation of NLRP3 inflammasome after intracerebral hemorrhage (ICH) ictus exacerbates neuroinflammation and brain injury. We hypothesized that inhibition of NLRP3 by OLT1177 (dapansutrile), a novel NLRP3 inflammasome inhibitor, could reduce brain edema and attenuate brain injury in experimental ICH., Methods: ICH was induced by injection of autologous blood into basal ganglia in mice models. Sixty-three C57Bl/6 male mice were randomly grouped into the sham, vehicle, OLT1177 (Dapansutrile, 200 mg/kg intraperitoneally) and treated for consecutive three days, starting from 1 h after ICH surgery. Behavioral test, brain edema, brain water content, blood-brain barrier integrity and vascular permeability, cell apoptosis, and NLRP3 and its downstream protein levels were measured., Results: OLT1177 significantly reduced cerebral edema after ICH and contributed to the attenuation of neurological deficits. OLT1177 could preserve blood-brain barrier integrity and lessen vascular leakage. In addition, OLT1177 preserved microglia morphological shift and significantly inhibited the activation of caspase-1 and release of IL-1β. We also found that OLT1177 can protect against neuronal loss in the affected hemisphere., Conclusions: OLT1177 (dapansutrile) could significantly attenuate the brain edema after ICH and effectively alleviate the neurological deficit. This result suggests that the novel NLRP3 inhibitor, OLT1177, might serve as a promising candidate for the treatment of ICH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Malignant cerebral edema (MCE) is a severe condition characterized by rapid neurological deterioration and a potentially poor prognosis. Scoring systems including the malignant brain edema (MBE) score, Enhanced Detection of Edema in Malignant Anterior Circulation Stroke score (EDEMA), and modified EDEMA score, have been developed to predict MCE in patients with large hemispheric infarction (LHI). We aimed to externally validate and comparethe predictive efficacy of these scores in LHI patients within 48 h of onset and not undergoing reperfusion therapy., Methods: Demographic, clinical and radiological data were retrospectively collected from LHI patients within 48 h of onset and not receiving reperfusion therapy. Patients were divided into MCE and non-MCE group. The calibration, discrimination, and clinical practicability of the three scores were verified using Hosmer-Lemeshow goodness-of-fit test, receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Finally, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were applied to determine the discrimination performance of the three scores., Results: A total of 314 patients were included in the study, with 122 cases being MCE patients. The Hosmer-Lemeshow goodness-of-fit test showed excellent fitting ability across the MBE (p = 0.36), EDEMA (p = 0.61), and modified EDEMA scores (p = 0.62) in our patients. The MBE, EDEMA, and modified EDEMA scores had the AUCs of 0.855 (95 % CI 0.818-0.898), 0.782 (95 % CI 0.727-0.837) and 0.878 (95 % CI 0.844-0.919) respectively. The MBE (NRI, 0.33; 95 % CI, 0.11-0.56, p = 0.003 and IDI, 0.11; 95 % CI, 0.03-0.18; p = 0.004) and modified EDEMA scores (NRI, 1.10; 95 % CI, 0.94-1.26; p < 0.001 and IDI, 0.17; 95 % CI, 0.13-0.20, p < 0.001) showed better performance than the EDEMA score. DCA demonstrated that the modified EDEMA score outperformed the other two scores, possessing heightened clinical usefulness., Conclusions: The MBE, EDEMA, and modified EDEMA scores for predicting MCE are also applicable in non-revascularization LHI patients within 48 h of onset. Both the MBE and modified EDEMA scores demonstrated higher predictive validity as predictive tools for MCE in LHI patients than the EDEMA score. Furthermore, the modified EDEMA score could be a suitable prediction tool in Chinese patients for its excellent clinical utility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Identify MR features predictive of poor outcomes in non-oncologic pediatric PRES., Method: A six-year search of all non-oncologic pediatric patients with clinical and MR features of PRES was performed. Modified Rankin scores were used to classify clinical outcomes into good versus poor, then clinical and MR features were compared among groups. Univariate and multivariate analysis was performed to identify MR predictors of poor outcomes for various imaging features, and p-values < 0.05 were considered statistically significant., Results: One hundred and forty-one patients (mean age 10.1 ± 3.0 years, male to female ratio 1:1.1) were included. Clinically, nephrotic syndrome (p = 0.03), focal deficits (p = 0.04), longer hospitalization (p < 0.001), and mechanical ventilation (p < 0.001) were significantly associated with poor outcomes. Univariate analysis revealed that deep grey matter nuclei (OR = 5.29, 95 % CI: 1.6-18.0) and cerebellar edema patterns (OR = 3.49, 95 % CI: 1.3-9.5), cytotoxic edema (OR = 63.6, 95 % CI:16.5-244.2), hemorrhage (OR = 16.58, 95 % CI: 4.3-64.2), and severe PRES patterns (OR = 11.0, 95 % CI: 3.5-34.7) on MR were all significantly associated with poor outcomes (p-values = 0.008 and 0.014, <0.001, <0.001, and < 0.001, respectively). This remained true for cytotoxic edema (OR = 84.26, 95 % CI: 17.3-410.9, p-value < 0.001) and hemorrhage (OR = 44.56, 95 % CI: 6.9-289.7, p-value < 0.001) on multivariate analysis., Conclusion: Diffusion restriction and hemorrhage on initial MR scans were the two independent predictors of poor outcomes in non-oncologic pediatric patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Neuroinflammation induced by early brain injury (EBI) seriously affects the prognosis of patients after subarachnoid hemorrhage (SAH). Pyroptosis can aggravate inflammatory injury by promoting the secretion of inflammatory cytokines. Meanwhile, STAT3 plays a critical role in the inflammatory response of EBI after SAH. However, whether it plays a pyroptotic role in SAH is mainly unknown. This study aimed to explore the mechanism of STAT3 in pyroptosis in EBI after SAH. C57BL/6J mice were used to establish the SAH model. Brain tissues were collected at different time points for q-RT-PCR and western blot to detect the expression level of STAT3. After intracerebroventricular injection of STAT3 inhibitor S3I-201, they were divided into sham, SAH, SAH + Vehicle, and SAH + S3I-201. Then, the SAH grade, cerebral edema content, blood-brain barrier (BBB) damage, and neurological scores of mice in each group were detected. qRT-PCR and western blot were used to detect related genes and proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of IL-18 and IL-1β. Immunofluorescence staining was used to observe the expression level of proteins. At the same time, S3I-201 was added to the primary neuron cells of the culture medium containing OxyHb to simulate the in vitro experiment, and the relevant indicators consistent with the in vivo experiment were detected. The expression of STAT3 was upregulated after SAH. Inhibition of STAT3 with S3I-201 attenuated neurological deficits, cerebral edema, and BBB damage after SAH. In addition, S3I-201 can also reduce the expression of pyroptosis-related inflammasomes such as GSDMD, NLRP3, Caspase 1, and AIM2 after SAH and the neurological damage caused by IL-18 and IL-1β. Further studies have shown that STAT3 regulates pyroptosis by promoting the nuclear translocation of NF-κB p65. Our finding demonstrated that STAT3 regulates neuronal pyroptosis in EBI after SAH. Inhibition of STAT3 may be a potential target to attenuate the damage that triggers neuroinflammation after SAH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Glutamate stimuli and hyperactivation of its receptor are predominant determinants of ischemia-induced cytotoxic cerebral edema, which is closely associated with protein nanoparticle (PN)-induced increases in osmotic pressure. Herein, we investigated the electrochemical and mechanical mechanisms underlying the neuron swelling induced by PNs via the co-activation of N-methyl-D-aspartate receptor subunit (NMDAR) and excitatory metabotropic glutamate receptors (mGluRs)., Results: We observed that co-activation of ionic glutamate receptor NMDAR and Group I metabotropic mGluRs promoted alteration of PN-induced membrane potential and increased intracellular osmosis, which was closely associated with calcium and voltage-dependent ion channels. In addition, activation of NMDAR-induced calmodulin (CaM) and mGluR downstream diacylglycerol (DAG)/protein kinase C α (PKCα) were observed to play crucial roles in cytotoxic hyperosmosis. The crosstalk between CaM and PKCα could upregulate the sensitivity and sustained opening of sulfonylurea receptor 1 (SUR1)-transient receptor potential cation channel subfamily M member 4 (TRPM4) and transmembrane protein 16 A (TMEM16A) channels, respectively, maintaining the massive Na + /Cl - influx, and the resultant neuron hyperosmosis and swelling. Intracellular PNs and Na + /Cl - influx were found to be as potential targets for cerebral edema treatment, using the neurocyte osmosis system and a cerebral ischemic rat model., Conclusions: This study highlights PNs as a key factor in "electrochemistry-tension" signal transduction controlling Na + /Cl - ion channels and increased osmotic pressure in ischemia-induced cytotoxic edema. Moreover, enhanced sensitivity in both Na + and Cl - ion channels also has a crucial role in cerebral edema., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Dexamethasone, a long-acting potent glucocorticoid, is one of the most widely used medications in neurosurgery. In this paper, the authors recount the history of dexamethasone's rise in neurosurgery and discuss its use in brain tumors in the context of emerging neuro-oncological immunotherapies. In 1958, Glen E. Arth synthesized a 16-alpha-methylated analog of cortisone (dexamethasone) for treatment of rheumatoid arthritis. Joseph Galicich, a neurosurgery resident at the time, applied the rheumatological drug to neurosurgery. He gave doses to patients who had undergone craniotomy for tumor removal and saw their paresis improve, midline shift resolve, and mortality rates decrease. He advocated for clinical trials and the drug became a mainstay in neurosurgery. As neuro-oncological treatments evolve to include immunotherapy, the immunosuppressive effects of dexamethasone are becoming an unwanted effect. The question then becomes: how does one treat the patient's symptoms if the only drug that has been used throughout history may become a detriment to their oncological treatment? Since its discovery, dexamethasone has maintained an impressive staying power in the field, acting as a standard drug for cerebral edema for more than 60 years. However, with the advent of immunotherapy, research is warranted to evaluate ways of treating symptomatic edema in the context of modern neuro-oncological therapies.

Traumatic brain injury (TBI) is recognized as an important risk factor for cognitive deficits. The present study was designed to determine the potential neuroprotective effects of chrysin, a natural flavonoid compound, against TBI-induced spatial cognitive decline and the possible mechanisms involved. Oral administration of chrysin (25, 50, or 100 mg/kg/day) was initiated in rats immediately following the induction of the diffuse TBI model using the weight-dropping Marmarou model. Spatial cognitive ability, hippocampal synaptic plasticity, blood-brain barrier (BBB) permeability, brain water content, and histological changes were assessed at scheduled time points. The animals subjected to TBI exhibited spatial cognitive decline in the Morris water maze (MWM) test, which was accompanied by inhibition of hippocampal long-term potentiation (LTP) induction at the perforant path-dentate gyrus (PP-DG) synapses. Additionally, TBI caused BBB disruption, brain edema, and neuronal loss. Interestingly, treatment with chrysin (especially in the dose of 100 mg/kg) alleviated all the above-mentioned neuropathological changes related to TBI. The results provide evidence that chrysin improves TBI-induced spatial cognitive decline, which may be partly related to the amelioration of hippocampal synaptic dysfunction, alleviation of BBB disruption, reduction of brain edema, and prevention of neuronal loss., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Edema, characterized by brain swelling, is a common response observed in various brain injuries. Timely detection of edema is crucial to mitigate the associated risks and improve patient care. This study evaluates the efficacy of CEREBO®, a non-invasive machine learning-powered near-infrared spectroscopy (mNIRS) based device, in detecting edema. The study was conducted on 234 participants with suspected head injuries who underwent simultaneous CEREBO® scans and CT head scans. The results of the study showed that CEREBO® effectively identified edematous lobes, achieving a sensitivity of 95.7%, specificity of 97%, and accuracy of 96.9% for cases with intracranial hemorrhage (ICH). Additionally, for cases without ICH, the device exhibited a sensitivity of 100%, specificity of 97.2%, and accuracy of 97.2%. Two cases were reported where CEREBO® failed to detect edematous ICH. The study highlights the potential of CEREBO® as a valuable tool for early detection of pre-symptomatic edema and ICH, enabling timely interventions and improved patient care. The findings support the reliability of near-infrared spectroscopy as a diagnostic modality for edema., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Intracerebral hemorrhage (ICH) is a stroke subtype characterized by non-traumatic rupture of blood vessels in the brain, resulting in blood pooling in the brain parenchyma. Despite its lower incidence than ischemic stroke, ICH remains a significant contributor to stroke-related mortality, and most survivors experience poor outcomes that significantly impact their quality of life. ICH has been accompanied by various complex pathological damage, including mechanical damage of brain tissue, hematoma mass effect, and then leads to inflammatory response, thrombin activation, erythrocyte lysis, excitatory amino acid toxicity, complement activation, and other pathological changes. Accumulating evidence has demonstrated that activation of complement cascade occurs in the early stage of brain injury, and the excessive complement activation after ICH will affect the occurrence of secondary brain injury (SBI) through multiple complex pathological processes, aggravating brain edema, and pathological brain injury. Therefore, the review summarized the pathological mechanisms of brain injury after ICH, specifically the complement role in ICH, and its related pathological mechanisms, to comprehensively understand the specific mechanism of different complements at different stages after ICH. Furthermore, we systematically reviewed the current state of complement-targeted therapies for ICH, providing a reference and basis for future clinical transformation of complement-targeted therapy for ICH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rationale: Iodinated contrast agents are extensively employed in clinical settings, with allergic reactions and renal impairment being the most prevalent adverse events. Contrast-induced encephalopathy (CIE) can present with heterogeneous clinical features, making diagnosis challenging. Prior studies on CIE have primarily documented rapid recovery within several days. However, this paper describes a case of CIE in a patient whose clinical symptoms took 3 months to fully abate., Patient Concerns: A female patient, aged 54 years, received drug-coated balloon therapy for stenosis in a branch of the anterior descending coronary artery. Unfortunately, the patient developed CIE, which initially manifested as visual disturbances and subsequently progressed to gastrointestinal and limb movement issues, as well as an altered mental status, all of which occurred within a 24-hour period during hospitalization., Diagnoses: The patient was diagnosed with CIE after cerebral hemorrhage, and cerebral edema was ruled out based on the history of contrast medium administration and radiographic exams., Interventions and Outcomes: Dexamethasone (10 mg/d), mannitol (100 mL/d), betahistine (500 mL), trazodone (25 mg), and hydration supplementation were given to treat CIE-related symptoms. Aspirin and clopidogrel were administered for the management of the cardiovascular ailment. The neurologist prescribed neurotrophic agents, namely, cytarabine and methylcobalamin, based on the cerebral magnetic resonance imaging findings. Despite the treatment, the patient's ocular symptoms, including blurry vision, diplopia, and impaired intraocular retraction, persisted. Furthermore, the patient's mental state was altered, and she continued to exhibit a depressive state during her 1-month follow-up visit., Lessons: CIE is a comparatively infrequent ailment, and its prompt identification and management are of paramount importance. Although the treatments for CIE are primarily symptomatic, it is crucial to acknowledge that the symptoms may not always subside quickly within a short duration. In conjunction with pharmacotherapy, counseling should be offered to address patients' mental health., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients resuscitated from cardiac arrest have variable severity of primary hypoxic ischemic brain injury (HIBI). Signatures of primary HIBI on brain imaging and electroencephalography (EEG) include diffuse cerebral edema and burst suppression with identical bursts (BSIB). We hypothesize distinct phenotypes of primary HIBI are associated with increasing cardiopulmonary resuscitation (CPR) duration., Methods: We identified from our prospective registry of both in-and out-of-hospital CA patients treated between January 2010 to January 2020 for this cohort study. We abstracted CPR duration, neurological examination, initial brain computed tomography gray to white ratio (GWR), and initial EEG pattern. We considered four phenotypes on presentation: awake; comatose with neither BSIB nor cerebral edema (non-malignant coma); BSIB; and cerebral edema (GWR ≤ 1.20). BSIB and cerebral edema were considered as non-mutually exclusive outcomes. We generated predicted probabilities of brain injury phenotype using localized regression., Results: We included 2,440 patients, of whom 545 (23%) were awake, 1,065 (44%) had non-malignant coma, 548 (23%) had BSIB and 438 (18%) had cerebral edema. Only 92 (4%) had both BSIB and edema. Median CPR duration was 16 [IQR 8-28] minutes. Median CPR duration increased in a stepwise manner across groups: awake 6 [3-13] minutes; non-malignant coma 15 [8-25] minutes; BSIB 21 [13-31] minutes; cerebral edema 32 [22-46] minutes. Predicted probability of phenotype changes over time., Conclusions: Brain injury phenotype is related to CPR duration, which is a surrogate for severity of HIBI. The sequence of most likely primary HIBI phenotype with progressively longer CPR duration is awake, coma without BSIB or edema, BSIB, and finally cerebral edema., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

1,2-Dichloroethane (1,2-DCE) is a pervasive environmental pollutant found in ambient and residential air, as well as ground and drinking water. Brain edema is the primary pathological consequence of 1,2-DCE overexposure. We found that microRNA (miRNA)-29b dysregulation after 1,2-DCE exposure can aggravate brain edema by suppressing aquaporin 4 (AQP4). Moreover, circular RNAs (circRNAs) can regulate the expression of downstream target genes through miRNA, and affect protein function. However, circRNAs' role in 1,2-DCE-induced brain edema via miR-29b-3p/AQP4 axis remains unclear. To address the mechanism's bottleneck, we explored the circRNA-miRNA-mRNA network underlying 1,2-DCE-driven astrocyte swelling in SVG p12 cells by circRNA sequencing, electron microscopy and isotope 3 H labeling combined with the 3-O-methylglucose uptake method. The results showed that 25 and 50 mM 1,2-DCE motivated astrocyte swelling, characterized by increased water content, enlarged cell vacuoles, and mitochondrial swelling. This was accompanied by miR-29b-3p downregulation and AQP4 upregulation. We verified that AQP4 were negatively regulated by miR-29b-3p in 1,2-DCE-induced astrocyte swelling. Also, circRNA sequencing highlighted that circBCL11B was upregulated by 1,2-DCE. This was manifested as circBCL11B overexpression playing an endogenous competitive role via upregulating AQP4 by binding to miR-29b-3p, thus leading to astrocyte swelling. Conversely, circBCL11B knockdown reversed the 1,2-DCE-motivated AQP4 upregulation and alleviated the cell swelling. Finally, we demonstrated that the circBCL11B was targeted to miR-29b-3p by fluorescence in situ hybridization and dual-luciferase reporter assay. In conclusion, our findings indicate that circBCL11B acts as a competing endogenous RNA to facilitate 1,2-DCE-caused astrocyte swelling via miR-29b-3p/AQP4 axis. These observations provide new insight into the epigenetic mechanisms underlying 1,2-DCE-induced brain edema., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)