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Background: The early prediction of cerebral edema changes in patients with spontaneous intracerebral hemorrhage (SICH) may facilitate earlier interventions and result in improved outcomes. This study aimed to develop and validate machine learning models to predict cerebral edema changes within 72 h, using readily available clinical parameters, and to identify relevant influencing factors. Methods: An observational study was conducted between April 2021 and October 2023 at the Quzhou Affiliated Hospital of Wenzhou Medical University. After preprocessing the data, the study population was randomly divided into training and internal validation cohorts in a 7:3 ratio (training: N = 150; validation: N = 65). The most relevant variables were selected using Support Vector Machine Recursive Feature Elimination (SVM-RFE) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms. The predictive performance of random forest (RF), GDBT, linear regression (LR), and XGBoost models was evaluated using the area under the receiver operating characteristic curve (AUROC), precision–recall curve (AUPRC), accuracy, F1-score, precision, recall, sensitivity, and specificity. Feature importance was calculated, and the SHapley Additive exPlanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) methods were employed to explain the top-performing model. Results: A total of 84 (39.1%) patients developed cerebral edema changes. In the validation cohort, GDBT outperformed LR and RF, achieving an AUC of 0.654 (95% CI: 0.611–0.699) compared to LR of 0.578 (95% CI, 0.535–0.623, DeLong: p = 0.197) and RF of 0.624 (95% CI, 0.588–0.687, DeLong: p = 0.236). XGBoost also demonstrated similar performance with an AUC of 0.660 (95% CI, 0.611–0.711, DeLong: p = 0.963). However, in the training set, GDBT still outperformed XGBoost, with an AUC of 0.603 ± 0.100 compared to XGBoost of 0.575 ± 0.096. SHAP analysis revealed that serum sodium, HDL, subarachnoid hemorrhage volume, sex, and left basal ganglia hemorrhage volume were the top five most important features for predicting cerebral edema changes in the GDBT model. Conclusion: The GDBT model demonstrated the best performance in predicting 72-h changes in cerebral edema. It has the potential to assist clinicians in identifying high-risk patients and guiding clinical decision-making. [ABSTRACT FROM AUTHOR]

Hyponatremia is the most common electrolyte abnormality encountered in critically ill patients and is linked to heightened morbidity, mortality, and healthcare resource utilization. However, its causal role in these poor outcomes and the impact of treatment remain unclear. Plasma sodium is the main determinant of plasma tonicity; consequently, hyponatremia commonly indicates hypotonicity but can also occur in conjunction with isotonicity and hypertonicity. Plasma sodium is a function of total body exchangeable sodium and potassium and total body water. Hypotonic hyponatremia arises when total body water is proportionally greater than the sum of total body exchangeable cations, that is, electrolyte-free water excess; the latter is the result of increased intake or decreased (kidney) excretion. Hypotonic hyponatremia leads to water movement into brain cells resulting in cerebral edema. Brain cells adapt by eliminating solutes, a process that is largely completed by 48 h. Clinical manifestations of hyponatremia depend on its biochemical severity and duration. Symptoms of hyponatremia are more pronounced with acute hyponatremia where brain adaptation is incomplete while they are less prominent in chronic hyponatremia. The authors recommend a physiological approach to determine if hyponatremia is hypotonic, if it is mediated by arginine vasopressin, and if arginine vasopressin secretion is physiologically appropriate. The treatment of hyponatremia depends on the presence and severity of symptoms. Brain herniation is a concern when severe symptoms are present, and current guidelines recommend immediate treatment with hypertonic saline. In the absence of significant symptoms, the concern is neurologic sequelae resulting from rapid correction of hyponatremia which is usually the result of a large water diuresis. Some studies have found desmopressin useful to effectively curtail the water diuresis responsible for rapid correction. [ABSTRACT FROM AUTHOR]

Background: Posterior reversible encephalopathy syndrome is a rare neurological syndrome that refers to reversible subcortical vasogenic brain edema disorder in patients with acute neurological symptoms. Case presentation: Whether there is a direct causal relationship between pancreatitis and posterior reversible encephalopathy syndrome needs further study. We here report a 39-year-old Chinese woman who was diagnosed with pancreatitis followed by vision disturbance. The patient was finally diagnosed with posterior reversible encephalopathy syndrome. On the basis of this rare case, we analyzed the causes of visual disturbance and proposed diagnostic ideas. Conclusions: For posterior reversible encephalopathy syndrome, early identification and treatment of the primary disease are particularly important. Imaging and clinical characteristics in posterior reversible encephalopathy syndrome are usually reversible. [ABSTRACT FROM AUTHOR]

Meningiomas are among the most common primary tumors of the central nervous system. In the past several decades, many researchers have emphasized the importance of radiographic findings and their possible role in predicting the various aspects of the meningioma biology. One of the factors most commonly analyzed with respect to the lesions' clinical behavior is peritumoral brain edema (PTBE), not only one of the most common signs associated with meningiomas, but also a significant clinical problem. Radiographic predictors of PTBE are usually noted as being the size of the tumor, its location, irregular margins, heterogeneity, and the peritumoral arachnoid plane with its pial vascular recruitment. Here, we review the available literature on the topic of these radiographic predictors of PTBE formation, we analyze the methodology of the research conducted, and we highlight the many controversies still present. Indeed, the evidence about PTBE pathogenesis, predictive factors, and clinical significance still seems to be mostly inconclusive, despite intense research in the area. We believe that by highlighting the many inconsistencies in the methodology used, we can showcase how little is actually known about the pathogenesis of PTBE, which in turn has important clinical implications. Additionally, we provide several MR images of intracranial meningiomas from our own practice which, we believe, showcase the unpredictable nature of PTBE, and demonstrate vividly the topics we discuss. [ABSTRACT FROM AUTHOR]

Purpose: This research aimed to create a machine learning model for clinicalradiomics that utilizes unenhanced computed tomography images to assess the likelihood of malignant cerebral edema (MCE) in individuals suffering from acute ischemic stroke (AIS). Methods: The research included 179 consecutive patients with AIS from two different hospitals. These patients were randomly assigned to training (n = 143) and validation (n = 36) sets with an 8:2 ratio. Using 3DSlicer software, the radiomics features of regions impacted by infarction were derived from unenhanced CT scans. The radiomics features linked to MCE were pinpointed through a consistency test, Student's t test and the least absolute shrinkage and selection operator (LASSO) method for selecting features. Clinical parameters associated with MCE were also identified. Subsequently, machine learning models were constructed based on clinical, radiomics, and clinical-radiomics. Ultimately, the efficacy of these models was evaluated by measuring the operating characteristics of the subjects through their area under the curve (AUCs). Results: Logistic regression (LR) was found to be the most effective machine learning algorithm, for forecasting the MCE. In the training and validation cohorts, the AUCs of clinical model were 0.836 and 0.773, respectively, for differentiating MCE patients; the AUCs of radiomics model were 0.849 and 0.818, respectively; the AUCs of clinical and radiomics model were 0.912 and 0.916, respectively. Conclusion: This model can assist in predicting MCE after acute ischemic stroke and can provide guidance for clinical treatment and prognostic assessment. [ABSTRACT FROM AUTHOR]

Objective: Brain tumors represent some of the most treatment refractory cancers, and there is a clinical need for additional treatments for these tumors. Domesticated dogs are the only other mammalian species which commonly develop spontaneous brain tumors, making them an ideal model for investigating novel therapies. Histotripsy is a non-thermal ultrasonic ablation method that emulsifies tissue through acoustic cavitation. The primary objectives of this prospective study were to assess the feasibility and safety of histotripsy to ablate naturally occurring canine brain tumors. Secondary endpoints included characterization of magnetic resonance imaging (MRI) responses to histotripsy treatment, and exploratory immunogenomic tumor response analyses. Methods: The study design utilized a treat and resect paradigm, where tumors were approached using craniotomy, partially ablated with histotripsy delivered through the cranial defect, imaged with MRI, and then resected. Dogs were evaluated with clinical, brain MRI, immunopathologic, and genomic examinations before treatment, intraoperatively, and 1, 14, and 42 days post-treatment. Here we report the results of the three dogs with meningiomas, all of which were treated with a custom eight element 1 MHz histotripsy transducer at a pulse repetition frequency of 100 Hz and a treatment dosage of 400 pulses/point. Results: Histotripsy was successfully delivered to all dogs, resulting in histopathologic evidence of ablations that were sharply demarcated from untreated tumor, with measured treatments approximating planned volumes in 2/3 dogs. One dog experienced an adverse event consisting of transient cerebral edema that was possibly attributable to histotripsy. Histotripsy ablations could be grossly visualized and identified on MRI, with features consistent with hemorrhage and necrosis. Significant expression or upregulation of the damage associated molecular pattern HMGB1, cytokine-cytokine receptor interaction, and NF-κb signaling pathways were observed in histotripsy treated tumors. Conclusion: Ablation of canine meningiomas with histotripsy through an open cranial window was feasible and clinically well tolerated. [ABSTRACT FROM AUTHOR]

Background: The early prediction of cerebral edema changes in patients with spontaneous intracerebral hemorrhage (SICH) may facilitate earlier interventions and result in improved outcomes. This study aimed to develop and validate machine learning models to predict cerebral edema changes within 72 h, using readily available clinical parameters, and to identify relevant influencing factors. Methods: An observational study was conducted between April 2021 and October 2023 at the Quzhou Affiliated Hospital of Wenzhou Medical University. After preprocessing the data, the study population was randomly divided into training and internal validation cohorts in a 7:3 ratio (training: N = 150; validation: N = 65). The most relevant variables were selected using Support Vector Machine Recursive Feature Elimination (SVM-RFE) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms. The predictive performance of random forest (RF), GDBT, linear regression (LR), and XGBoost models was evaluated using the area under the receiver operating characteristic curve (AUROC), precision--recall curve (AUPRC), accuracy, F1-score, precision, recall, sensitivity, and specificity. Feature importance was calculated, and the SHapley Additive exPlanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) methods were employed to explain the top-performing model. Results: A total of 84 (39.1%) patients developed cerebral edema changes. In the validation cohort, GDBT outperformed LR and RF, achieving an AUC of 0.654 (95% CI: 0.611-0.699) compared to LR of 0.578 (95% CI, 0.535-0.623, DeLong: p = 0.197) and RF of 0.624 (95% CI, 0.588-0.687, DeLong: p = 0.236). XGBoost also demonstrated similar performance with an AUC of 0.660 (95% CI, 0.611-0.711, DeLong: p = 0.963). However, in the training set, GDBT still outperformed XGBoost, with an AUC of 0.603 ± 0.100 compared to XGBoost of 0.575 ± 0.096. SHAP analysis revealed that serum sodium, HDL, subarachnoid hemorrhage volume, sex, and left basal ganglia hemorrhage volume were the top five most important features for predicting cerebral edema changes in the GDBT model. Conclusion: The GDBT model demonstrated the best performance in predicting 72-h changes in cerebral edema. It has the potential to assist clinicians in identifying high-risk patients and guiding clinical decision-making. [ABSTRACT FROM AUTHOR]

Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca2+-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca2+ imaging in vivo [Postnatal Day (P)12-17] and in acute brain slices (P8-12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca2+ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca2+-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain. [ABSTRACT FROM AUTHOR]

Background and purpose: Early diagnosis and the refinement of treatment of patients with intracranial meningiomas have brought quality of life (QoL) and neurocognitive functioning as outcome measures into focus. The aim of this study is a comprehensive assessment of neurocognitive function, quality of life and the presence of depression in meningioma patients before and after surgery. Methods: Patients with MRI diagnosis of intracranial meningioma and indication for surgery were prospectively included. A clinical neuropsychologist performed neurocognitive assessments within 3 months before and 12 months after surgery. The test battery included investigation of selective and divided attention, verbal and figural memory, executive functioning, and word fluency. Self-report questionnaires to assess depressive symptoms, QoL, and disease coping were administered. Raw values and t-values were compared pre-and postoperatively. Outcome was stratified by tumor- and peritumoral brain edema (PTBE) volumes, postoperative resolution of PTBE and WHO grade. The study included 18 predominantly female patients (83%) with a median age of 59 years and mostly CNS WHO grade 1 meningiomas (83%). Results: There was a significant postoperative improvement in the ability to selectively react under stress, in working memory and improved delayed reproduction of verbal and visual memory content. QoL improved regarding a reduction in physical problems, an improvement in energy, and social functioning. There was a trend towards worse preoperative scores in all tests, and greater postoperative improvement in patients with PTBE. Tumor volume had no effect on the measured outcome. The patients did not suffer from depressive symptoms before the surgery but improved postoperatively and most patients had an active, problem-oriented coping strategy. Conclusion: Resection of intracranial meningiomas leads to an improvement in multiple neurocognitive domains and QoL. There is a trend towards poorer preoperative neurocognitive functioning and greater postoperative improvement in patients with PTBE. Depression appears to play a minor role in the context of neurocognitive functioning and disease coping. [ABSTRACT FROM AUTHOR]

The water channel aquaporin-4 (AQP4) is crucial for water balance in the mammalian brain. AQP4 has two main canonical isoforms, M23, which forms supramolecular structures called Orthogonal Arrays of Particles (OAP) and M1, which does not, along with two extended isoforms (M23ex and M1ex). This study examines these isoforms' roles, particularly AQP4ex, which influences water channel activity and localization at the blood-brain barrier. Using mice lacking both AQP4ex isoforms (AQP4ex-KO) and lacking both AQP4M23 isoforms (OAP-null) mice, we explored brain water dynamics under osmotic stress induced by an acute water intoxication (AWI) model. AQP4ex-KO mice had lower basal brain water content than WT and OAP-null mice. During AWI, brain water content increased rapidly in WT and AQP4ex-KO mice, but was delayed in OAP-null mice. AQP4ex-KO mice had the highest water content increase at 20 min. Immunoblot analysis showed stable total AQP4 in WT mice initially, with increases at 30 min. AQP4ex and its phosphorylated form (p-AQP4ex) levels rose quickly, but the p-AQP4ex/AQP4ex ratio dropped at 20 min. AQP4ex-KO mice showed a compensatory rise in canonical AQP4 at 20 min post-AWI. These findings highlight the important role of AQP4ex in water content dynamics in both normal and pathological states. To evaluate brain waste clearance, amyloid-β (Aβ) removal was assessed using a fluorescent Aβ intra-parenchyma injection model. AQP4ex-KO mice demonstrated markedly impaired Aβ clearance, with extended diffusion distances and reduced fluorescence in cervical lymph nodes, indicating inefficient drainage from the brain parenchyma. Mechanistically, the polarization of AQP4 at astrocytic endfeet is essential for efficient clearance flow, aiding interstitial fluid movement into the CSF and lymphatic system. In AQP4ex-KO mice, disrupted polarization forces reliance on slower, passive diffusion for solute clearance, significantly reducing Aβ removal efficiency and altering extracellular space dynamics. Our results underscore the importance of AQP4ex in both brain water homeostasis and solute clearance, particularly Aβ. These findings highlight AQP4ex as a potential therapeutic target for enhancing waste clearance mechanisms in the brain, which could have significant implications for treating brain edema and neurodegenerative diseases like Alzheimer's. [ABSTRACT FROM AUTHOR]

Purpose: Acute necrotizing encephalopathy (ANE), a rare and severe brain disorder, is typically linked to prior infections. ANE predominantly affects children, with most reported cases attributed to viral infections. However, instances of bacterial-induced ANE are infrequent. Here, we present a case of adult-onset ANE associated with bacterial infection. Case descriptions: The patient exhibited a hyperinflammatory state following a urinary tract bacterial infection, with neurological function rapidly declining into a coma as the illness progressed. Gram culture of blood suggested Escherichia coli infection. A magnetic resonance imaging (MRI) scan of the brain showed symmetrical hyperintense lesions involving bilateral thalami and pons in T2-weighted and fluid-attenuated inversion recovery images. These lesions also presented with diffuse cerebral edema and diffusion restriction and subacute hemorrhage. Based on clinical symptoms and typical brain MRI, ANE was diagnosed, and the patient underwent immunotherapy. Conclusions: This case underscores the occurrence of ANE triggered by bacterial infection, expanding our understanding of the pathogens associated with this condition. It suggests that ANE may be an immune-mediated disorder rather than solely an infectious disease. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) has high mortality. Early brain injury (EBI) is responsible for unfavorable outcomes for patients with SAH. The protective involvement of autophagy in hemorrhagic stroke has been proposed. The transcription factor EB (TFEB) can increase autophagic flux by promoting autophagosome formation and autophagosome-lysosome fusion, and dysregulation of TFEB activity might induce the development of several diseases. However, the biological functions of TFEB in EBI after SAH remain unknown. We established an animal model of SAH by the modified endovascular perforation method. Expression of TFEB and autophagy required genes was measured by western blotting and immunofluorescence staining. SAH grading, brain water content and neurobehavioral functions were evaluated at 24 h post-SAH. Neuronal apoptosis in cerebral cortex was assessed by TUNEL staining and Fluoro Jade B staining. TFEB was downregulated in SAH rats, and its overexpression reduced brain edema and ameliorated neurological deficits of SAH rats. Additionally, the neuronal apoptosis induced by SAH was inhibited by TFEB overexpression. Moreover, TFEB overexpression promoted autophagy after SAH. TFEB overexpression promotes autophagy to inhibit neuronal apoptosis, brain edema and neurological deficits post-SAH. [ABSTRACT FROM AUTHOR]

Background: Aquaporin‐4 (AQP4), predominantly expressed in astrocytes, has been implicated in the development of brain edema following ischemic events. However, its role in post‐stroke neuroinflammation is not fully understood. Methods: Using a middle cerebral artery occlusion (MCAO) mouse model, we assessed AQP4's role in post‐stroke inflammation. Brain tissue slices from male C57BL/6 mice were subjected to immunohistochemistry and western blot post‐MCAO. Additionally, primary astrocytes were isolated for quantitative real‐time PCR and immunofluorescence assays to evaluate the expression of inflammatory markers glial fibrillary acidic protein (GFAP) and AQP4. AQP4 modulation was achieved using viral knockdown and overexpression methods. Neuronal damage was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests in co‐culture studies. Results: MCAO mice exhibited a significant upregulation in GFAP. This reactive astrogliosis corresponded with an elevation in inflammatory markers. AQP4 expression responded to this inflammatory trend, peaking at 6 h after OGD and returning to baseline levels at 24 and 48 h. Co‐culture experiments revealed that AQP4(+) astrocytes exacerbated injury in OGD‐treated neurons, as evidenced by increased TUNEL positivity and apoptotic events. Conversely, AQP4(−) astrocytes appeared to have a protective effect. Knockdown of AQP4 resulted in reduced post‐OGD inflammatory response, whereas AQP4 overexpression intensified the injury to neurons post‐OGD. In vivo experiments also confirmed that AQP4 inhibitor TGN‐020 reduced and overexpression of AQP4 increased behavioral abnormalities and brain infarcts. Conclusion: Our findings underscore AQP4's pivotal role in modulating post‐stroke neuroinflammation. Targeting AQP4 may present a novel therapeutic avenue for mitigating ischemia‐induced neuronal damage. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Parkinson's disease (PD) may benefit from deep brain stimulation (DBS). Perifocal brain edema sometimes occurs after DBS surgery, but it is transient and does not affect the final prognosis. Transient deterioration of cognitive function has been reported in patients with frontal edema in the first postoperative week. This study aimed to investigate the effect of Goreisan in preventing edematous changes after DBS and determine the influence of edema on cognition. Methods: We included 29 patients with PD who underwent bilateral subthalamic nucleus (STN) DBS and who were divided into 2 groups: those using (11 patients) and those not using Goreisan (18 patients). At 1 week postoperatively, all patients underwent magnetic resonance imaging. We measured the volume of edema either in the frontal white matter or STN on fluid‐attenuated inversion recovery (FLAIR) images. Finally, brain edema, motor function, and cognitive function were compared between the groups with and without Goreisan. Results: In the FLAIR image 1 week postoperatively, the average postoperative frontal subcortical edema (FE) volume of the group with Goreisan was significantly lower than that without Goreisan (2249 ± 2186 mm3, 6261 ± 7213 mm3, respectively, p = 0.023). Multivariate analysis with age, preoperative Mini‐Mental State Examination (MMSE) score, FE, and peri‐STN edema (SE) as factors, and MMSE at 1 week postoperatively as the dependent variable showed that preoperative MMSE score and SE were significant as associated factors. Conclusions: FE after DBS surgery may be alleviated using Goreisan. SE and preoperative MMSE scores were associated with MMSE scores 1 week postoperatively. Trial Registration: Not applicable [ABSTRACT FROM AUTHOR]

Following ischemic stroke, substance P (SP)-mediated neurogenic inflammation is associated with profound blood-brain barrier (BBB) dysfunction, cerebral edema, and elevated intracranial pressure (ICP). SP elicits its effects by binding the neurokinin 1 tachykinin receptor (NK1-R), with administration of an NK1-R antagonist shown to ameliorate BBB dysfunction and cerebral edema in rodent and permanent ovine stroke models. Given the importance of reperfusion in clinical stroke, this study examined the efficacy of NK1-R antagonist treatment in reducing cerebral edema and ICP in an ovine model of transient middle cerebral artery occlusion (tMCAo). Anesthetized sheep (n = 24) were subject to 2-hours tMCAo and randomized (n = 6/group) to receive early NK1-R treatment (days 1–3 post-stroke), delayed NK1-R treatment (day 5 post-stroke), or saline vehicle. At 6-days post-stroke animals were re-anaesthetized and ICP measured, followed by MRI to evaluate infarction, edema and BBB dysfunction. Following both early and delayed NK1-R antagonist administration, ICP was significantly reduced on day 6 compared to vehicle animals (p < 0.05), accompanied by a reduction in cerebral edema, midline shift and BBB dysfunction (p < 0.05). This study demonstrates that NK1-R antagonist treatment is an effective novel therapy for cerebral edema and elevated ICP following stroke in an ovine model, warranting future clinical evaluation. [ABSTRACT FROM AUTHOR]

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body's oxygen at rest. Oxygen deprivation to the brain can lead to loss of consciousness within seconds and death within minutes. Recent studies have identified regions of the brain with spontaneous episodic hypoxia, referred to as "hypoxic pockets". Hypoxia can also result from impaired blood flow due to conditions such as heart disease, blood clots, stroke, or hemorrhage, as well as from reduced oxygen intake or excessive oxygen consumption caused by factors like low ambient oxygen, pulmonary diseases, infections, inflammation, and cancer. Severe hypoxia in the brain can manifest symptoms similar to Parkinson's disease (PD), including cerebral edema, mood disturbances, and cognitive impairments. Additionally, the development of PD appears to be closely associated with hypoxia and hypoxic pathways. This review seeks to investigate the molecular interactions between hypoxia and PD, emphasizing the pathological role of hypoxic pathways in PD and exploring their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) scans of acute cerebral hemorrhage are often characterized by high-density imaging with occasional mixed density and low-density imaging features. Possible reasons for this are a lack of blood coagulation, extravasation of cerebrospinal fluid, and brain tissue edema. It is rarely due to the accumulation of lipid components associated with hyperlipidemia. In the present case, preoperative lipid tests and the intraoperative finding of a large amount of milky white fluid surrounding the hematoma confirmed that the low-density imaging surrounding the hematoma visible on the CT scan represented a rare case of lipid accumulation. [ABSTRACT FROM AUTHOR]

Objective: To identify brain edema in fetuses with Chiari II malformation using a multiparametric approach including structural T2-weighted, diffusion tensor imaging (DTI) metrics, and MRI-based radiomics. Methods: A single-center retrospective review of MRI scans obtained in fetuses with Chiari II was performed. Brain edema cases were radiologically identified using the following MR criteria: brain parenchymal T2 prolongation, blurring of lamination, and effacement of external CSF spaces. Fractional anisotropy (FA) values were calculated from regions of interest (ROI), including hemispheric parenchyma, internal capsule, and corticospinal tract, and compared group-wise. After 1:1 age matching and manual single-slice 2D segmentation of the fetal brain parenchyma using ITK-Snap, radiomics features were extracted using pyradiomics. Areas under the curve (AUCs) of the features regarding discriminating subgroups were calculated. Results: Ninety-one fetuses with Chiari II underwent a total of 101 MRI scans at a median gestational age of 24.4 weeks and were included. Fifty scans were visually classified as Chiari II with brain edema group and showed significantly reduced external CSF spaces compared to the nonedema group (9.8 vs. 18.3 mm, p < 0.001). FA values of all used ROIs were elevated in the edema group (p < 0.001 for all ROIs). The 10 most important radiomics features showed an AUC of 0.81 (95%CI: 0.71, 0.91) for discriminating between Chiari II fetuses with and without edema. Conclusions: Brain edema in fetuses with Chiari II is common and radiologically detectable on T2-weighted fetal MRI sequences, and DTI-based FA values and radiomics features provide further evidence of microstructure differences between subgroups with and without edema. Clinical relevance statement: A more severe phenotype of fetuses with Chiari II malformation is characterized by prenatal brain edema and more postnatal clinical morbidity and disability. Fetal brain edema is a promising prenatal MR imaging biomarker candidate for optimizing the risk-benefit evaluation of selection for fetal surgery. Key Points: Brain edema of fetuses prenatally diagnosed with Chiari II malformation is a common, so far unknown, association. DTI metrics and radiomics confirm microstructural differences between the brains of Chiari II fetuses with and without edema. Fetal brain edema may explain worse motor outcomes in this Chiari II subgroup, who may substantially benefit from fetal surgery. [ABSTRACT FROM AUTHOR]

Objectives: Ischemic edema is associated with worse clinical outcomes, especially in large infarcts. Computed tomography (CT)–based densitometry allows direct quantification of absolute edema volume (EV), which challenges indirect biomarkers like midline shift (MLS). We compared EV and MLS as imaging biomarkers of ischemic edema and predictors of malignant infarction (MI) and very poor clinical outcome (VPCO) in early follow-up CT of patients with large infarcts. Materials and methods: Patients with anterior circulation stroke, large vessel occlusion, and Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 were included. VPCO was defined as modified Rankin scale (mRS) ≥ 5 at discharge. MLS and EV were quantified at admission and in follow-up CT 24 h after admission. Correlation was analyzed between MLS, EV, and total infarct volume (TIV). Multivariable logistic regression and receiver operating characteristics curve analyses were performed to compare MLS and EV as predictors of MI and VPCO. Results: Seventy patients (median TIV 110 mL) were analyzed. EV showed strong correlation to TIV (r = 0.91, p < 0.001) and good diagnostic accuracy to classify MI (EV AUC 0.74 [95%CI 0.61–0.88] vs. MLS AUC 0.82 [95%CI 0.71–0.94]; p = 0.48) and VPCO (EV AUC 0.72 [95%CI 0.60–0.84] vs. MLS AUC 0.69 [95%CI 0.57–0.81]; p = 0.5) with no significant difference compared to MLS, which did not correlate with TIV < 110 mL (r = 0.17, p = 0.33). Conclusion: EV might serve as an imaging biomarker of ischemic edema in future studies, as it is applicable to infarcts of all volumes and predicts MI and VPCO in patients with large infarcts with the same accuracy as MLS. Clinical relevance statement: Utilization of edema volume instead of midline shift as an edema parameter would allow differentiation of patients with large and small infarcts based on the extent of edema, with possible advantages in the prediction of treatment effects, complications, and outcome. Key Points: • CT densitometry–based absolute edema volume challenges midline shift as current gold standard measure of ischemic edema. • Edema volume predicts malignant infarction and poor clinical outcome in patients with large infarcts with similar accuracy compared to MLS irrespective of the lesion extent. • Edema volume might serve as a reliable quantitative imaging biomarker of ischemic edema in acute stroke triage independent of lesion size. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the associations of macrophage migration inhibitory factor (MIF), toll-like receptors 2 and 4 (TLR2/4), and matrix metalloproteinase 9 (MMP9) with 3-month poor outcome, death, and malignant cerebral edema (MCE) in patients with large hemispheric infarction (LHI). Methods: Patients with LHI within 24 h of onset were enrolled consecutively. Serum MIF, TLR2/4, and MMP9 concentrations on admission were measured. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. MCE was defined as a decreased level of consciousness, anisocoria and midline shift > 5 mm or basal cistern effacement, or indications for decompressive craniectomy during hospitalization. The cutoff values for MIF/MMP9 were obtained from the receiver operating characteristic curve. Results: Of the 130 patients with LHI enrolled, 90 patients (69.2%) had 3-month poor outcome, and MCE occurred in 55 patients (42.3%). Patients with serum MIF concentrations ≤ 7.82 ng/mL for predicting 3-month poor outcome [adjusted odds ratio (OR) 2.827, 95% confidence interval (CI) 1.144–6.990, p = 0.024] also distinguished death (adjusted OR 4.329, 95% CI 1.841–10.178, p = 0.001). Similarly, MMP9 concentrations ≤ 46.56 ng/mL for predicting 3-month poor outcome (adjusted OR 2.814, 95% CI 1.236–6.406, p = 0.014) also distinguished 3-month death (adjusted OR 3.845, 95% CI 1.534–9.637, p = 0.004). Conclusions: Lower serum MIF and MMP9 concentrations at an early stage were independently associated with 3-month poor outcomes and death in patients with LHI. These findings need further confirmation in larger sample studies. [ABSTRACT FROM AUTHOR]

Background: Patients with traumatic brain injury (TBI) with large contusions make up a specific TBI subtype. Because of the risk of brain edema worsening, elevated cerebral perfusion pressure (CPP) may be particularly dangerous. The pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) are new promising perfusion targets based on cerebral autoregulation, but they reflect the global brain state and may be less valid in patients with predominant focal lesions. In this study, we aimed to investigate if patients with TBI with significant contusions exhibited a different association between PRx, CPP, and CPPopt in relation to functional outcome compared to those with small/no contusions. Methods: This observational study included 385 patients with moderate to severe TBI treated at a neurointensive care unit in Uppsala, Sweden. The patients were classified into two groups: (1) significant contusions (> 10 mL) and (2) small/no contusions (but with extra-axial or diffuse injuries). The percentage of good monitoring time (%GMT) with intracranial pressure > 20 mm Hg; PRx > 0.30; CPP < 60 mm Hg, within 60–70 mm Hg, or > 70 mm Hg; and ΔCPPopt less than − 5 mm Hg, ± 5 mm Hg, or > 5 mm Hg was calculated. Outcome (Glasgow Outcome Scale-Extended) was assessed after 6 months. Results: Among the 120 (31%) patients with significant contusions, a lower %GMT with CPP between 60 and 70 mm Hg was independently associated with unfavorable outcome. The %GMTs with PRx and ΔCPPopt ± 5 mm Hg were not independently associated with outcome. Among the 265 (69%) patients with small/no contusions, a higher %GMT of PRx > 0.30 and a lower %GMT of ΔCPPopt ± 5 mm Hg were independently associated with unfavorable outcome. Conclusions: In patients with TBI with significant contusions, CPP within 60–70 mm Hg may improve outcome. PRx and CPPopt, which reflect global cerebral pressure autoregulation, may be useful in patients with TBI without significant focal brain lesions but seem less valid for those with large contusions. However, this was an observational, hypothesis-generating study; our findings need to be validated in prospective studies before translating them into clinical practice. [ABSTRACT FROM AUTHOR]

Background: The efficacy of melatonin in reducing vasogenic and cytotoxic edema was investigated using a model of permanent middle cerebral artery occlusion (pMCAO). Methods: Rats underwent pMCAO, followed by intravenous administration of either melatonin (5 mg/kg) or a vehicle 10 min post-insult. Brain infarction and edema were assessed, and Western blot analyses were conducted to examine the expression levels of aquaporin-4 (AQP4), metalloproteinase-9 (MMP-9), and the neurovascular tight-junction protein ZO-1 upon sacrifice. The permeability of the blood–brain barrier (BBB) was measured using spectrophotometric quantification of Evans blue dye leakage. Results: Compared to controls, melatonin-treated rats exhibited a significant reduction in infarct volume by 26.9% and showed improved neurobehavioral outcomes (p < 0.05 for both). Melatonin treatment also led to decreased Evans blue dye extravasation and brain edema (p < 0.05 for both), along with lower expression levels of AQP4 and MMP-9 proteins and better preservation of ZO-1 protein (p < 0.05 for all). Conclusions: Therefore, melatonin offers neuroprotection against brain swelling induced by ischemia, possibly through its modulation of AQP4 and MMP-9 activities in glial cells and the extracellular matrix (ECM) during the early phase of ischemic injury. [ABSTRACT FROM AUTHOR]

Background and Aims: Idiopathic intracranial hypertension (IIH) is a rare neurological disorder in the pediatric population which is defined as an increase in intracranial pressure (ICP) without the presence of brain parenchymal lesions, hydrocephalus, or central nervous system infection. In this study, we have determined the magnetic resonance imaging (MRI) findings in IIH patients. Methods: A comprehensive literature search was conducted using the electronic databases including Web of Sciences, Scopus, and Pubmed to identify suitable and relevant articles using keyword search methods. The search included keywords such as "idiopathic intracranial hypertension," "pseudotumor cerebri," "MRI," and "pediatrics." The search was limited to the available publications up to January 2024. Results: MRI plays a crucial role in diagnosing IIH by excluding secondary causes and revealing neuroimaging findings associated with elevated ICP. Despite fewer studies in children compared to adults, MRI serves as a cornerstone in identifying traditional neuroradiological markers such as empty sella turcica, posterior globe flattening, optic nerve tortuosity, optic nerve sheath distension, and transverse venous sinus stenosis. Additional subtle markers include increased Meckel's cave length, cerebellar tonsillar herniation, and slit‐like ventricles, although these are less reliable. Diffusion‐weighted imaging does not typically show cerebral ADC value changes indicative of cerebral edema in pediatric IIH. Conclusion: MRI findings provide valuable non‐invasive diagnostic indicators that facilitate early detection, clinical management, and potential surgical intervention in pediatric IIH. The reliability of these MRI markers underscores their importance in clinical practice. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of mild therapeutic hypothermia combined with stereotactic aspiration of spontaneous intracerebral hematoma on neurological function, inflammatory markers, cerebral hematoma, and cerebral edema in patients with severe cerebral hemorrhage. The clinical data of 86 patients with severe cerebral hemorrhage treated at our hospital between March 2020 and January 2022 were retrospectively analyzed. The patients were grouped according to their treatment plans: the control group consisted of 40 patients who underwent stereotactic aspiration of the spontaneous intracerebral hematoma, whereas the study group consisted of 46 patients who received adjuvant mild therapeutic hypothermia in addition to the aforementioned treatment. Clinical efficacy, neurological function (NIHSS score), daily living ability (BI score), cerebral hematoma, cerebral edema, cerebral hemodynamics (PI, RI, Vm, Vd), inflammatory markers (IL-6, IL-8, TNF-α, hs-CRP), oxidative stress indicators (SOD, MDA, 8-iso-PGF2α), serum-related factors (MMP-9, ICAM-1, ET-1, NO), and prognosis were compared between the groups. The total efficacy rate in the study group (95.65%) was significantly higher than that in the control group (77.50%) (P < 0.05). Post-treatment NIHSS scores, intracranial hematoma volume, perihematoma edema volume, cerebral edema volume, RI, serum IL-6, IL-8, TNF-α, hs-CRP, MDA, and 8-iso-PGF2α levels were significantly lower in both groups, with the study group showing even greater reductions. The BI score and PI, Vm, Vd, SOD, and NO levels were significantly higher in the study group (P < 0.05). At the 6-month follow-up, the prognosis of patients in the intervention group was significantly better than that of patients in the control group (P < 0.05). The combination of mild therapeutic hypothermia with stereotactic aspiration of a spontaneous intracerebral hematoma has demonstrated efficacy in the treatment of severe cerebral hemorrhage. This approach effectively reduces cerebral hematoma and edema, improves daily living ability, alleviates neurological deficits, regulates cerebral hemodynamics, suppresses inflammatory responses and oxidative stress, modulates serum-related factor levels, and enhances patient prognosis. [ABSTRACT FROM AUTHOR]

Poor outcome following traumatic acute subdural hematoma (ASDH) is associated with the severity of the primary injury and secondary injury including cerebral edema and ischemia. However, the underlying secondary injury mechanism contributing to elevated intracranial pressure (ICP) and high mortality rate remains unclear. Cerebral edema occurs in response to the exposure of the intracellular fixed charge density (FCD) after cell death, causing ICP to increase. The increased ICP from swollen tissue compresses blood vessels in adjacent tissue, restricting blood flow and leading to ischemic damage. We hypothesize that the mass occupying effect of ASDH exacerbates the ischemic injury, leading to ICP elevation, which is an indicator of high mortality rate in the clinic. Using FEBio (febio.org) and triphasic swelling biomechanics, this study modeled clinically relevant ASDHs and simulated post-traumatic brain swelling and ischemia to predict ICP. Results showed that common convexity ASDH significantly increased ICP by exacerbating ischemic injury, and surgical removal of the convexity ASDH may control ICP by preventing ischemia progression. However, in cases where the primary injury is very severe, surgical intervention alone may not effectively decrease ICP, as the contribution of the hematoma to the elevated ICP is insignificant. In addition, interhemispheric ASDH, located between the cerebral hemispheres, does not significantly exacerbate ischemia, supporting the conservative surgical management generally recommended for interhemispheric ASDH. The joint effect of the mass occupying effect of the blood clot and resulting ischemia contributes to elevated ICP which may increase mortality. Our novel approach may improve the fidelity of predicting patient outcome after motor vehicle crashes and traumatic brain injuries due to other causes. [ABSTRACT FROM AUTHOR]

Background: The Coiled-Coil Domain-Containing Protein 88 A (CCDC88A) gene encodes the actin-binding protein Girdin, which plays important roles in maintaining the actin cytoskeleton and in cell migration and was recently associated with a specific form of epileptic encephalopathy. Biallelic protein-truncating variants of CCDC88A have been considered responsible for progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO)-like syndrome. To date, only three consanguineous families with loss-of-function homozygous variants in the CCDC88A gene have been reported. The described patients share many clinical features, such as microcephaly, neonatal hypotonia, seizures, profound developmental delay, face and limb edema, and dysmorphic features, with a similar appearance of the eyes, nose, mouth, and fingers. Case presentation: We report on a child from a nonconsanguineous family who presented with profound global developmental delay, severe epilepsy, and brain malformations, including subcortical band heterotopia. The patient harbored two heterozygous pathogenic variants in the trans configuration in the CCDC88A gene, which affected the coiled-coil and C-terminal domains. Conclusions: We detail the clinical and cerebral imaging data of our patient in the context of previously reported patients with disease-causing variants in the CCDC88A gene, emphasizing the common phenotypes, including cortical malformations, that warrant screening for sequence variants in this gene. [ABSTRACT FROM AUTHOR]

Background: Early severe cerebral edema and chronic hydrocephalus are the primary cause of poor prognosis in patients with subarachnoid hemorrhage (SAH). This study investigated the role of cerebrospinal fluid (CSF) inflammatory cytokines and coagulation factors in the development of severe cerebral edema and chronic hydrocephalus in patients with SAH. Methods: Patients with SAH enrolled in this study were categorized into mild and severe cerebral edema groups based on the Subarachnoid Hemorrhage Early Brain Edema Score at admission. During long-term follow-up, patients were further classified into hydrocephalus and non-hydrocephalus groups. CSF samples were collected within 48 h post-SAH, and levels of inflammatory cytokines and coagulation factors were measured. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with severe cerebral edema and chronic hydrocephalus. The correlation between inflammatory cytokines and coagulation factors was further investigated and validated in a mouse model of SAH. Results: Seventy-two patients were enrolled in the study. Factors from the extrinsic coagulation pathway and inflammatory cytokines were associated with both severe cerebral edema and chronic hydrocephalus. Coagulation products thrombin-antithrombin complexes (TAT) and fibrin, as well as inflammatory cytokines IL-1β, IL-2, IL-5, IL-7, and IL-4, were independently associated with severe cerebral edema. Additionally, Factor VII, fibrin, IL-2, IL-5, IL-12, TNF-α, and CCL-4 were independently associated with chronic hydrocephalus. A positive correlation between extrinsic coagulation factors and inflammatory cytokines was observed. In the SAH mouse model, tissue plasminogen activator was shown to alleviate neuroinflammation and cerebral edema, potentially by restoring glymphatic-meningeal lymphatic function. Conclusions: Elevated levels of inflammatory cytokines and extrinsic coagulation pathway factors in the CSF are associated with the development of early severe cerebral edema and chronic hydrocephalus following SAH. These factors are interrelated and may contribute to post-SAH glymphatic-meningeal lymphatic dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Chronic and acute mountain sickness is known worldwide, but most of the available information comes from the eastern continent (Himalayas) without taking into account the west which has the most recent group located at altitude, the Andes. The aim of this study was to synthesize the evidence on the prevalence of acute and chronic mountain sickness in Latin American countries (LATAM). Methods: A systematic search of the variables of interest was performed until July 8, 2023 in the Web of Science, Scopus, PubMed and Embase databases. We included studies that assessed the prevalence of mountain sickness in high-altitude inhabitants (>1500 m.a.s.l) who lived in a place more than 12 months. These were analyzed by means of a meta-analysis of proportions. To assess sources of heterogeneity, subgroup analyses and sensitivity analyses were performed by including only studies with low risk of bias and excluding extreme values (0 or 10,000 ratio). PROSPERO (CRD42021286504). Results: Thirty-nine cross-sectional studies (10,549 participants) met the inclusion criteria. We identified 5 334 and 2 945 events out of 10,000 with acute and chronic mountain sickness in LATAM countries. The most common physiological alteration was polycythemia (2,558 events), while cerebral edema was the less common (46 events). Clinical conditions were more prevalent at high altitudes for both types of MS. Conclusion: Acute mountain sickness (AMS) occurs approximately in 5 out of 10 people at high altitude, while chronic mountain sickness (CMS) occurs in 3 out of 10. The most frequent physiological alteration was polycythemia and the least frequent was cerebral edema. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the inhibitory effect of Polydatin (PD) on endoplasmic reticulum (ER) stress following subarachnoid hemorrhage (SAH) and to elucidate the underlying mechanisms. Methods: A standard intravascular puncture model was established to mimic SAH in mice. Neurological functions were assessed using neurological scoring, Grip test, and Morris water maze. Brain edema and Evans blue extravasation were measured to evaluate blood-brain barrier permeability. Western blot and quantitative real-time polymerase chain reaction (PCR) analyses were performed to examine protein and mRNA expressions related to ER stress. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to detect cell apoptosis, and transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum. Results: The results indicated that PD significantly reduced brain edema and Evans blue extravasation after SAH, improving neurological function. Compared to the SAH group, the expression levels of ER stress-related proteins including glucose-regulated protein 78 (GRP78), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were significantly lower in the PD-treated group. Moreover, PD significantly enhances the protein expression of Sirtuin 1 (SIRT1). Validation with sh-SIRT1 confirmed the critical role of SIRT1 in ER stress, with PD's inhibitory effect on ER stress being dependent on SIRT1 expression. Additionally, PD attenuated ER stress-mediated neuronal apoptosis and SAHinduced ferroptosis through upregulation of SIRT1. Conclusion: PD alleviates ER stress following SAH by upregulating SIRT1 expression, thereby mitigating early brain injury. The protective effects of PD are mediated through SIRT1, which inhibits ER stress and reduces neuronal apoptosis and ferroptosis. [ABSTRACT FROM AUTHOR]

Brain edema robustly increases mortality and hinders functional recovery after acute ischemic stroke. However, there are currently no effective therapies available for treating or preventing it. The unchecked opening of the transient receptor potential M4 (TRPM4) channel results in an excessive influx of Na+ and water, which contributes significantly to the formation of brain edema after ischemic stroke. 9‐phenanthrol (9‐Phe), a potent TRPM4 inhibitor, has limited clinical applicability due to its potential cytotoxicity and poor solubility. A brain‐targeting T7 (HAIYPRH)‐modified lipid nanoparticle (LNP) encapsulated 9‐Phe (9‐Phe@T7‐LNP) is designed and synthesized to improve the physicochemical properties and pharmacokinetic properties of 9‐Phe for treating brain edema in vivo. These results demonstrated that 9‐Phe@T7‐LNP can penetrate the intact blood‐brain barrier (BBB) in normal mice and target the brain parenchyma. Moreover, 9‐Phe@T7‐LNP effectively reduced infarct volume and brain edema, prevented neuronal loss and BBB disruption, improved survival, and facilitated neurological function recovery after transient middle cerebral artery occlusion in mice. Additionally, 9‐Phe@T7‐LNP scavenged oxygen‐free radicals and prevented neuronal apoptosis in cultured neurons subjected to oxygen and glucose deprivation/reperfusion. In summary, these findings showed that 9‐Phe@T7‐LNP holds strong potential as a promising targeted therapy for brain edema after stroke, providing superior pharmacological neuroprotection against brain edema. [ABSTRACT FROM AUTHOR]

Introduction: Endovascular treatment (EVT) is a therapeutic option for cerebral venous thrombosis (CVT); however, its benefit over conservative medical management has not been proven. Whether the current patient selection practices are appropriate for EVT is unclear. Methods: This was a nationwide study of the 2016–2020 National Inpatient Sample database. Adult CVT patients and EVT treatments were identified. Patient demographics, medical comorbidities, CVT risk factors, and CVT manifestations were identified. Presence of radiographic signs of advanced and severe CVT (venous infarction, cerebral edema, and intracranial hemorrhage) was recorded. Primary and secondary outcomes were good discharge outcomes and in-hospital mortality, respectively. Results: A total of 17,130 CVT patients were identified, and 56.7% had good discharge outcomes, while 4.6% died during hospitalization. 945 (5.5%) received EVT, and EVT patients were more likely to have cerebral infarction (35.4 vs. 21.8%, p < 0.001), edema (35.4 vs. 20.1%, p < 0.001), and hemorrhage (37.6 vs. 19.7%, p < 0.001). After multivariable adjustments, EVT for patients without infarction, edema, or hemorrhage was moderately associated with higher odds of good outcomes (OR 1.86 [95% CI 0.98–3.53], p = 0.059) and resulted in zero deaths. However, with the increasing burden of radiographic signs of advanced CVT measured by the cumulative presence of infarction, edema, and hemorrhage, EVT was associated with decreasing odds of good outcomes and increasing odds of in-hospital mortality compared to medical management (interaction p = 0.046 and 0.029, respectively). Conclusions: EVT may lead to higher rates of favorable hospitalization outcomes in patients who have not yet developed overt parenchymal manifestations of backpressure changes; presence of infarction, edema, and hemorrhage may diminish the short-term effectiveness of EVT. [ABSTRACT FROM AUTHOR]

Glioblastomas synthesize, bear receptors for, and respond to bradykinin, triggering migration and proliferation. Since centrifugal migration into uninvolved surrounding brain tissue occurs early in the course of glioblastoma, this attribute defeats local treatment attempts and is the primary reason current treatments almost always fail. Stopping bradykinin-triggered migration would be a step closer to control of this disease. The recent approval and marketing of an oral plasma kallikrein inhibitor, berotralstat (Orladeyo™), and pending FDA approval of a similar drug, sebetralstat, now offers a potential method for reducing local bradykinin production at sites of bradykinin-mediated glioblastoma migration. Both drugs are approved for treating hereditary angioedema. They are ideal for repurposing as a treatment adjunct in glioblastoma. Furthermore, it has been established that peritumoral edema, a common problem during the clinical course of glioblastoma, is generated in large part by locally produced bradykinin via kallikrein action. Both brain edema and the consequent use of corticosteroids both shorten survival in glioblastoma. Therefore, by (i) migration inhibition, (ii) growth inhibition, (iii) edema reduction, and (iv) the potential for less use of corticosteroids, berotralstat may be of service in treatment of glioblastoma, slowing disease progression. This paper recounts the details and past research on bradykinin in glioblastoma and the rationale of treating it with berotralstat. [ABSTRACT FROM AUTHOR]

Aims: Incidence of acute mountain sickness (AMS) ranges from 40%–90%, with high‐altitude cerebral edema (HACE) representing a life‐threatening end stage of severe AMS. However, practical and convenient preventive strategies for HACE are lacking. Remote ischemic preconditioning (RIPC) has demonstrated preventive effects on ischemia‐ or hypoxia‐induced cardiovascular and cerebrovascular diseases. This study aimed to investigate the potential molecular mechanism of HACE and the application of RIPC in preventing HACE onset. Methods: A hypobaric hypoxia chamber was used to simulate a high‐altitude environment of 7000 meters. Metabolomics and metabolic flux analysis were employed to assay metabolite levels. Transcriptomics and quantitative real‐time PCR (q‐PCR) were used to investigate gene expression levels. Immunofluorescence staining was performed on neurons to label cellular proteins. The fluorescent probes Mito‐Dendra2, iATPSnFR1.0, and CMTMRos were used to observe mitochondria, ATP, and membrane potential in cultured neurons, respectively. TUNEL staining was performed to detect and quantify apoptotic cell death. Hematoxylin and eosin (H&E) staining was utilized to analyze pathological changes, such as tissue swelling in cerebral cortex samples. The Rotarod test was performed to assess motor coordination and balance in rats. Oxygen–glucose deprivation (OGD) of cultured cells was employed as an in vitro model to simulate the hypoxia and hypoglycemia induced by RIPC in animal experiments. Results: We revealed a causative perturbation of glucose metabolism in the brain preceding cerebral edema. Ischemic preconditioning treatment significantly reprograms glucose metabolism, ameliorating cell apoptosis and hypoxia‐induced energy deprivation. Notably, ischemic preconditioning improves mitochondrial membrane potential and ATP production through enhanced glucose‐coupled mitochondrial metabolism. In vivo studies confirm that RIPC alleviates cerebral edema, reduces cell apoptosis induced by high‐altitude hypoxia, and improves motor dysfunction resulting from cerebral edema. Conclusions: Our study elucidates the metabolic basis of HACE pathogenesis. This study provides a new strategy for preventing HACE that RIPC reduces brain edema through reprogramming metabolism, highlighting the potential of targeting metabolic reprogramming for neuroprotective interventions in neurological diseases caused by ischemia or hypoxia. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Superior vena cava syndrome (SVCS) is commonly caused by mediastinal malignancies. Early identification through clinical signs and imaging is critical to avoid complications including cerebral and laryngeal edema, and cardiogenic shock. We present a case of large cell neuroendocrine carcinoma causing superior and inferior vena cava compression that responded well to radiotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Elevated intracranial pressure (ICP) in patients with cerebral lesions has garnered considerable attention in research. It often manifests as a common symptom in conditions such as intracranial tumors, intracerebral hemorrhage, and cerebral edema. This paper provides an overview of ICP concepts, discusses the advantages and disadvantages of traditional monitoring methods, explores the physiological and anatomical aspects of the optic nerve sheath, examines the utility of ultrasound measurement of optic nerve sheath diameter (ONSD) in both nervous system and nonnervous system disorders, and outlines the cutoff values and normal ranges for assessing elevated ICP using ultrasound measurement of ONSD. The review underscores ultrasound measurement of ONSD as a promising noninvasive, safe, straightforward, and repeatable examination technique for various diseases. Nevertheless, the lack of standardized cutoff values for elevated ICP remains a challenge. Summarizing studies on optic nerve sheaths is crucial for enhancing the efficacy of ultrasound measurement of ONSD in assessing ICP. [ABSTRACT FROM AUTHOR]

Adapting the mechanical strength between the implant materials and the brain tissue is crucial for the postoperative treatment of glioblastoma. However, no related study has been reported. Herein, we report an injectable lipoic acid‑iron (LA-Fe) hydrogel (LFH) that can adapt to the mechanical strength of various brain tissues, including human brain tissue, by coordinating Fe3+ into a hybrid hydrogel of LA and its sodium salt (LANa). When LFH, which matches the mechanical properties of mouse brain tissue (337 ± 8.06 Pa), was injected into the brain resection cavity, the water content of the brain tissue was maintained at a normal level (77%). Similarly, LFH did not induce the activation or hypertrophy of glial astrocytes, effectively preventing brain edema and scar hyperplasia. Notably, LFH spontaneously degrades in the interstitial fluid, releasing LA and Fe3+ into tumor cells. The redox couples LA/DHLA (dihydrolipoic acid, reduction form of LA in cells) and Fe3+/Fe2+ would regenerate each other to continuously provide ROS to induce ferroptosis and activate immunogenic cell death. As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the efficacy of tumor-immunotherapy and promoted tumor ferroptosis. The injectable hydrogel that adapted the mechanical strength of tissues shed a new light for the tumor postoperative treatment. TOC Graph: The first injectable hydrogel that can adapt the mechanical strength of different brain tissues including human brain has been developed for the GBM postoperative treatment without the involvement of anti-tumor drugs by coordinating Fe3+ into the hybrid hydrogel of B vitamin lipoic acid (LA) and its sodium salt (LANa). [Display omitted] • By coordinating Fe3+ into the hybrid hydrogel of lipoic acid (LA) and its sodium salt (LANa) formed an injectable hydrogel. • The LA-Fe hydrogel (LFH) can adapt the mechanical strength of multiple brain tissues including human brain. • The LFH circumvented the foreign body reaction caused by material implantation, and effectively inhibited tumor recurrence. • As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the tumor-immunotherapy efficacy and promoted the tumor ferroptosis. [ABSTRACT FROM AUTHOR]

In patients suffering from focal drug-resistant epilepsy, intracranial explorations are the gold standard for identifying the epileptogenic zone and evaluating the possibility of a surgical resection. Amongst them, stereoelectroencephalography (SEEG), using depth electrodes, is a safe procedure. However, complications occur on average in 2% of cases, notably haemorrhages or infections. Vasogenic cerebral oedema constitutes a rarely reported complication. Amongst the 85 patients explored with SEEG between January 2017 and September 2023, three had a clinically and electrophysiologically relevant vasogenic cerebral oedema. In these three patients, the surgical procedure was uneventful. In all three as well, electrodes exploring areas away from the epileptogenic zone recorded some unexpected focal delta slowing with clinically asymptomatic superimposed discharges, a pattern so far only reported in cases of bleeding. Moreover, one patient experienced confusion 10 days after explantation. Post-explantation magnetic resonance imaging showed, in all three patients, a vasogenic oedema that fully resolved a few months later. We did not identify any contributing factors, and there were no particularities concerning the number of electrodes, their implantation site or the recording duration. Focal delta slowing and rhythmic discharges during SEEG can indicate a vasogenic oedema. Clinical consequences can occur after explantation. Evolution is favourable but this misleading pattern must be identified. [ABSTRACT FROM AUTHOR]

Brain edema is a critical complication arising from stroke and traumatic brain injury (TBI) with an important impact on patient recovery and can lead to long-term consequences. Therapeutic options to reduce edema progression are limited with variable patient outcomes. Aquaporin 4 (AQP4) is a water channel that allows bidirectional water diffusion across the astrocyte membrane and participates in the distinct phases of cerebral edema. The absence or inhibition of this channel has been demonstrated to ameliorate edema and brain damage. The endocannabinoid system (ECS) is a neuromodulator system with a wide expression in the brain and its activation has shown neuroprotective properties in diverse models of neuronal damage. This review describes and discusses the major features of ECS and AQP4 and their role during brain damage, observing that ECS stimulation reduces edema and injury size in diverse models of brain damage, however, the relationship between AQP4 expression and dynamics and ECS activation remains unclear. The research on these topics holds promising therapeutic implications for the treatment of brain edema following stroke and TBI. [ABSTRACT FROM AUTHOR]

A subarachnoid hemorrhage (SAH) is life-threatening bleeding into the subarachnoid space that causes brain damage. Growing evidence has suggested that melatonin provides neuroprotection following SAH. Exploring the mechanisms underlying melatonin-mediated neuroprotection contributes to its clinical application in SAH. The plasma and cerebrospinal fluid (CSF) were collected from SAH patients, and SAH mice were established via pre-chiasmatic injection. Circodz3 expression, levels of IL-1β and TNF-α, brain water content, neurological and beam-waling scores were determined. Ferroptosis was evaluated by analyzing levels of iron, lipid ROS, MDA, and GSH. The colocalization of circodz3 and Iba-1 was analyzed by immunofluorescence staining. Interaction of circodz3 and HuR was determined with RNA pull-down and RNA immunoprecipitation assays. Herein, we found that circodz3 was highly abundant in SAH patients and mice. Colocalization of circodz3 and Iba-1 in the left hemisphere of SAH mice suggested the implication of circodz3 in regulating microglia activation following SAH. Melatonin alleviated brain edema, neurological impairment, and microglia activation and inhibited circodz3 expression in SAH mice. Moreover, melatonin inhibited M1 polarization, oxidative stress and ferroptosis and restrained circodz3 expression in primary microglia following SAH. These effects were abrogated by circodz3 overexpression. Circodz3 knockdown inhibited ferroptosis and M1 polarization of BV2 microglia after SAH. Circodz3 interacted with HuR to facilitate β-Trcp1-mediated ubiquitination and degradation, thus restraining the expression of SLC7A11 and GPX4. Collectively, melatonin exerted neuroprotection following SAH via inhibiting ferroptosis and M1 polarization through the circodz3/HuR axis. Our study suggests potential application of melatonin in the treatment of SAH. Highlights: CircODZ3 is highly abundant in the plasma and cerebrospinal fluid from SAH patients. Melatonin protects against SAH by inhibiting circodz3 expression. Silencing of circodz3 inhibits ferroptosis and M1 polarization of BV2 microglia. Circodz3 interacts with HuR to promote its ubiquitination and degradation. Circodz3 degrades HuR to reduce SLC7A11 and GPX4 expression. [ABSTRACT FROM AUTHOR]

Interest in naturally occurring phytochemicals has been on the increase, they are believed to reduce the risk of brain disorders. Hispidulin (HN) is a phenolic flavonoid compound with various pharmacological and biological effects on the central nervous system. It belongs to the flavone class of flavonoids. It can be found in different plant materials, especially fruits and vegetables. The literature used in this review was collected from credible scientific databases including ScienceDirect, Scopus, PubMed, Google Scholar, and Hindawi without time restriction, using relevant keywords, such as HN, brain, central nervous system, flavonoids, and flavones. HN was discovered to possess pro-apoptotic properties, act as an antioxidant, inhibit cytokine production and toll-like receptor 4 expression, as well as impede nuclear factor kappa beta and mitogen-activated protein kinase B. HN was also found to inhibit lipid peroxidation in vitro and reduce brain edema in mice. These pharmacological potentials suggest that HN is a promising candidate for neuroprotection in CNS disorders like depression and epilepsy. This review provides an update on the scientific literature concerning how these activities could help provide various forms of neuroprotection in the CNS. Additional experimental data on the effects of HN in models of neurological disorders and neuroprotection should be explored further. Based on the current study, HN is a promising candidate for neuroprotection of the CNS. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) induces a complex sequence of apoptotic cascades and inflammatory responses, leading to neurological impairment. Transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel with high calcium permeability, has been implicated in neuronal apoptosis and inflammatory responses. This study used a mouse ICH model and neuronal cultures to examine whether TRPV1 activation exacerbates brain damage and neurological deficits by promoting neuronal apoptosis and neuroinflammation. ICH was induced by injecting collagenase in both wild‐type (WT) C57BL/6 mice and TRPV1−/− mice. Capsaicin (CAP; a TRPV1 agonist) or capsazepine (a TRPV1 antagonist) was administered by intracerebroventricular injection 30 min before ICH induction in WT mice. The effects of genetic deletion or pharmacological inhibition of TRPV1 using CAP or capsazepine on motor deficits, histological damage, apoptotic responses, blood–brain barrier (BBB) permeability, and neuroinflammatory reactions were explored. The antiapoptotic mechanisms and calcium influx induced by TRPV1 inactivation were investigated in cultured hemin‐stimulated neurons. TRPV1 expression was upregulated in the hemorrhagic brain, and TRPV1 was expressed in neurons, microglia, and astrocytes after ICH. Genetic deletion of TRPV1 significantly attenuated motor deficits and brain atrophy for up to 28 days. Deletion of TRPV1 also reduced brain damage, neurodegeneration, microglial activation, cytokine expression, and cell apoptosis at 1 day post‐ICH. Similarly, the administration of CAP ameliorated brain damage, neurodegeneration, brain edema, BBB permeability, and cytokine expression at 1 day post‐ICH. In primary neuronal cultures, pharmacological inactivation of TRPV1 by CAP attenuated neuronal vulnerability to hemin‐induced injury, suppressed apoptosis, and preserved mitochondrial integrity in vitro. Mechanistically, CAP reduced hemin‐stimulated calcium influx and prevented the phosphorylation of CaMKII in cultured neurons, which was associated with reduced activation of P38 and c‐Jun NH2‐terminal kinase mitogen‐activated protein kinase signaling. Our results suggest that TRPV1 inhibition may be a potential therapy for ICH by suppressing mitochondria‐related neuronal apoptosis. [ABSTRACT FROM AUTHOR]

response, which might lead to sudden rise in blood pressure (BP), causing intracranial hemorrhage, cerebral edema, and prolonged hospital stay. Dexmedetomidine has been shown to blunt the sympathoadrenal response to surgery. Aims and Objectives: The present study was undertaken to assess the efficacy and safety of dexmedetomidine in attenuating stress responses to skull pin holder application as compared to normal saline. Materials and Methods: After obtaining approval from the institutional ethics committee and written informed consent, patients of either sex undergoing elective craniotomy at the attached hospitals of Bangalore Medical College and Research Institute, Bengaluru, India, were randomized in a 1:1 ratio to receive normal saline or dexmedetomidine as premedication. Hemodynamic parameters, i.e., heart rate (HR), systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP), were monitored at various time points until 30 min after skull pin application. Data were analyzed using the chi-squared test, repeated measure ANOVA, unpaired t-test, and Mann--Whitney U test, wherever applicable. Results: A total of 52 patients were included in the study, with 26 patients in each group. All the baseline parameters were matched. As a stress response, a significant increase in HR was seen after intubation (90.69 bpm) and skull pin insertion (87.92 bpm) in the normal saline group. However, there was no significant variation in HR in the dexmedetomidine group over 30 min (69.19 bpm-74.15 bpm). Dexmedetomidine reduced HR significantly as compared to normal saline after intubation (P = 0.03). Dexmedetomidine lowered SBP and DBP as compared to baseline throughout 30 min without any excursions during intubation and skull pin insertion. The SBP was significantly lower in the dexmedetomidine group after intubation as compared to saline (P = 0.02). Although a reduction in SBP was noted after skull pin insertion in the dexmedetomidine group, it was not statistically significant than saline. No significant difference was noted in DBP, MAP, or blood glucose between the two groups. No incidents of hypotension and bradycardia were noted. Conclusion: Dexmedetomidine maintained basal HR throughout 30 min without any variations in response to intubation and skull pin insertion. It also reduced SBP and DBP over 30 min. HR and SBP were significantly lower in the dexmedetomidine group as compared to saline after intubation. The same effect was noted in the dexmedetomidine group as compared to saline after skull pin insertion, but it was not statistically significant. [ABSTRACT FROM AUTHOR]

Background and Objectives: Pediatric traumatic brain injury (pTBI) remains a major pediatric public health problem, despite well-developed injury prevention programs. The purpose of this study is to analyze the emergency surgical outcomes of pTBI in a single institute ten-year retrospective study to offer a real-world clinical result. Materials and Methods: Our institute presented a clinical retrospective, single-institute research study of 150 pediatric TBI cases that were diagnosed and underwent emergency surgical treatment from 2010 to 2019. Results: The incidence of radiological findings is detailed as follows: brain edema (30%, 45/150), followed by acute subdural hematoma (27.3%, 41/150), epidural hematoma (21.3%, 32/150), chronic subdural hemorrhage (10%, 15/150), skull fracture (6.7%, 10/150), and traumatic subarachnoid hemorrhage (4.7%, 7/150). Surgical intervention data revealed that decompressive craniectomy was still the main effective surgical method. The results showed longer hospital stays and higher morbidity rates in the brain edema, acute subdural hematoma, and chronic subdural hemorrhage groups, which were viewed as poor surgical outcome groups. Epidural hematoma, skull fracture and traumatic subarachnoid hemorrhage were categorized into good surgical outcome groups. Notably, the data revealed gross improvement in Glasgow Coma Scale/Score (GCS) evolution after surgical interventions, and the time to cranioplasty was a significant factor in the development of post-traumatic hydrocephalus (PTH). Conclusions: Our study provided real-world data for the distribution of etiology in pTBI and also categorized it into six groups, indicating disease-orientated treatment. In addition, our data supported that decompressive craniectomy (DC) remains a mainstay surgical treatment in pTBI and early cranioplasty could decrease the incidence of PTH. [ABSTRACT FROM AUTHOR]

Significant progress has been achieved in enhancing early outcomes for individuals with maple syrup urine disease (MSUD), a rare metabolic disorder that leads to the accumulation of branched‐chain amino acids leucine, isoleucine, and valine, where leucine is known as the primary neurotoxic metabolite. Newborn screening is helpful in early diagnosis and implementation of dietary treatment, thus reducing neurological deterioration and complications in young children. However, patients face the life‐long challenge of maintaining metabolic control through adherence to a strict low‐leucine diet to avoid long‐term consequences of chronic hyperleucinemia, which include cognitive deficits, mood disorders, and movement disorders. This case report exemplifies the complex involvement of MSUD in adult survivors. Despite presenting early in life, the patient thrived until the onset of psychiatric symptoms. The subject of this case is a 25‐year‐old woman with MSUD, who remained in her usual state of health until presentation to the emergency department (ED) with psychosis and altered mental status. However, due to a lack of medical records and poor communication, there was a delay in considering MSUD as a primary cause of her psychiatric symptoms. Although a genetics consultation was later arranged and efforts were made to decrease plasma leucine to the therapeutic range, these interventions proved inadequate in halting her deterioration in health. Her condition worsened within 72 h, culminating in her untimely death. This case emphasizes the comorbidity of psychiatric involvement in MSUD, which contributes to metabolic decompensation that can lead to cerebral edema and death. This case also highlights the pressing need for enhanced strategies for the acute management and long‐term care of MSUD patients with psychiatric involvement, particularly in scenarios where mental disturbance could lead to noncompliance. [ABSTRACT FROM AUTHOR]

Abstract Background Postoperative progressive cerebral edema and hemorrhage (PPCEH) are major complications after meningioma resection, yet their preoperative predictive studies are limited. The aim is to develop and validate a multiparametric MRI machine learning model to predict PPCEH after meningioma resection. Methods This retrospective study included 148 patients with meningioma. A stratified three-fold cross-validation was used to split the dataset into training and validation sets. Radiomics features from the tumor enhancement (TE) and peritumoral brain edema (PTBE) regions were extracted from T1WI, T2WI, and ADC maps. Support vector machine constructed different radiomics models, and logistic regression explored clinical risk factors. Prediction models, integrating clinical and radiomics features, were evaluated using the area under the curve (AUC), visualized in a nomogram. Results The radiomics model based on TE and PTBE regions (training set mean AUC: 0.85 (95% CI: 0.78–0.93), validation set mean AUC: 0.77 (95%CI: 0.63–0.90)) outperformed the model with TE region solely (training set mean AUC: 0.83 (95% CI: 0.76–0.91), validation set mean AUC: 0.73 (95% CI: 0.58–0.87)). Furthermore, the combined model incorporating radiomics features, and clinical features of preoperative peritumoral edema and tumor boundary adhesion, had the best predictive performance, with AUC values of 0.87 (95% CI: 0.80–0.94) and 0.84 (95% CI: 0.72–0.95) for the training and validation set. Conclusions We developed a novel model based on clinical characteristics and multiparametric radiomics features derived from TE and PTBE regions, which can accurately and non-invasively predict PPCEH after meningioma resection. Additionally, our findings suggest the crucial role of PTBE radiomics features in understanding the potential mechanisms of PPCEH.

Cerebral edema caused by blood–brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell–derived neural stem cell exosomes (hiPSC–NSC–Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC–NSC–Exos on blood–brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC–NSC–Exos mitigated neurological deficits, enhanced blood–brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC–NSC–Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α post–intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC–NSC–Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood–brain barrier integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood–brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Background: Clinically, ischemic reperfusion injury is the main cause of stroke injury. This study aimed to assess the effectiveness of fingolimod in suppressing inflammation caused by ischemic brain injury and explore its pharmacological mechanisms. Methods: In total, 75 male Sprague-Dawley rats were randomly and equally assigned to five distinct groups: sham, middle cerebral artery occlusion/ reperfusion (MCAO/R) surgery, fingolimod low-dose (F-L), fingolimod medium-dose (F-M), and fingolimod high-dose (F-H). Neurobehavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and the brain tissue drying-wet method were conducted to evaluate neurological impairment, cerebral infarction size, and brain water content. Enzyme-linked immunosorbent assay was employed to quantify pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) protein levels. Western blotting and immunohistochemical staining were performed to assess high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and nuclear factor kappa-B p65 (NF-κBp65) levels. Results: Rats in the F-L, F-M, and F-H groups exhibited lower Longa scores, reduced infarction volumes, and decreased brain edema than those in the MCAO/R group. Additionally, the F-L, F-M, and F-H groups exhibited lower serum levels of IL-1β, IL-6, and TNF-α than those of the MCAO/R group. Additionally, F-L, F-M, and F-H treatments resulted in decreased HMGB1, TLR4, and NF-κBp65 protein expression levels in the hippocampus of MCAO/R rats. Conclusions: Fingolimod was found to reduce ischemic brain injury in a dose-dependent manner. Moreover, it was also found to alleviate inflammation following ischemic brain injury via the HMGB1/TLR4/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: The dialysis disequilibrium syndrome (DDS) is a complication in those undergoing dialysis for chronic kidney disease (CKD) or acute kidney injury (AKI), characterized by nonspecific symptoms that may progress to coma and death secondary to cerebral edema. This syndrome is associated with rapid change in electrolytes during dialysis with changes in intracranial pressure (ICP) and may have a higher incidence in the elderly neurosurgical patient population. Methods: Literature review and illustrative case example. Results: A 62-year-old female presented with acute mental status change during hemodialysis (HD), with a history of a nonsurgical acute subdural hematoma (SDH) 10 days prior. Imaging showed a conversion of the acute SDH to chronic SDH of 12.2 mm in size with a 14.1 midline shift, for which she underwent a hemicraniectomy with SDH evacuation, with a gradual return to baseline. The literature review identified 5 publications meeting the inclusion criteria. Major theories of DDS include a reverse urea effect, intracerebral acidosis, idiogenic osmoles, and local inflammation. This complication may occur more frequently in the elderly neurosurgical patient population, likely due to age-related comorbidities, preexisting neurological insult, and increased permeability of the blood–brain barrier (BBB), leading to cerebral edema. Conclusion: DDS is a rare and potentially fatal complication of HD that may have a higher incidence in the elderly neurosurgical patient population, yet remains to be fully understood. Further study is recommended to characterize the pathophysiological mechanism and incidence of DDS in neurosurgical patients. [ABSTRACT FROM AUTHOR]