Investigating the therapeutic potential of nasal administration of mitochondria on blood-brain barrier integrity and vasogenic brain Edema in a rat ischemic stroke model.

SnRNA-seq reveals the ameliorative effects of optimized Xueyu Jingshen formula on high altitude cerebral edema by modulating energy metabolism, inflammation and BBB integrity.

Exosomes derived from neural stem cells contribute to cerebral ischemia/reperfusion injury via inhibiting autophagy in rats.

Targeting neuroinflammation in ischemic stroke: The promise of phytoconstituents.

Trends and disparities in cerebral edema-related mortality in the United States: A nationwide analysis using CDC WONDER data, 1999-2023.

A real-world pharmacovigilance study of modafinil events in the FDA Adverse Event Reporting System (FAERS).

Introduction: Ovarian cancer is one of the most common gynecological cancers in the United States. Common sites of distant metastasis from ovarian cancers and other cancers of Mullerian origin include the liver, pleura and lungs. However, metastasis to the brain remains exceptionally rare, ranging from 0.49 to 6.1%. Hence, the scarcity of such cases poses significant diagnostic and management challenges. Case Presentation: We present a case of an 80-year-old female who at the time of initial diagnosis presented with complaints of right leg pain, shortness of breath and cough. Imaging studies were remarkable for a pulmonary embolism, 2.5 cm mediastinal mass, pleural effusions, omental caking and an occlusive thrombus in the right greater saphenous vein. Malignancy was suspected in the setting of hypercoagulability. Biopsy of the omentum and pleural cytology revealed a high grade ovarian serous carcinoma. The patient received neoadjuvant chemotherapy followed by cytoreductive surgery and additional chemotherapy afterwards. She demonstrated good response to treatment with follow up PET without evidence of disease. Over the next four years, the patient was intermittently placed on chemotherapy when found to have elevated CA125 levels and PET scan showing small volume disease mostly in the pelvis. Six-years later, the patient presented to the oncology clinic with complaints of dizziness and imbalance for the past month. MRI brain showed a new left cerebellar mass with vasogenic edema and obstructive hydrocephalus. However, restaging CT chest, abdomen and pelvis showed minimal to no disease, with the only possible foci being a 1.2 cm paraaortic lymph node. The patient underwent left suboccipital craniotomy and cerebellar tumor resection with pathology showing metastatic carcinoma consistent with spread from a Mullerian primary. Conclusion: This case emphasizes the diagnostic complexity and evolving clinical course of Müllerian tumors. In a patient with a history of Mullerian tumor and new onset neurological symptoms, differential diagnosis should include metastasis to the brain, even with minimal to no active pelvic and systemic disease burden.

Berberine alleviates early brain injury after subarachnoid hemorrhage by inhibiting GSK3β-mediated CASP1-dependent pyroptosis.

Blood vessel hyperpermeability underlies a wide spectrum of potentially fatal diseases ranging from acute pulmonary edema to brain injuries such as ischemic stroke. Yet, effective strategies for rapid rehabilitation of the vascular endothelium to restore vascular homeostasis remain lacking. Here we developed an mRNA therapeutic encoding the vascular membrane structural protein VE-Cadherin (VEc), delivered via an anti-CD31 targeted lipid nanoparticle (aCD31/tLNP-VEc) directly to CD31+ vascular endothelial cells, for the quick restoration of vascular integrity. We showed that administration of a single dose of aCD31/tLNP-VEc significantly ameliorates pathological onsets in multiple mouse models of vascular hyperpermeability. In a bleomycin-induced lung edema model, we found aCD31/tLNP-VEc treatment significantly reduced fluid extravasation and decreased macrophage infiltrations. In a transient middle cerebral artery occlusion (tMCAO)-induced ischemic stroke model, aCD31/tLNP-VEc delivered post-injury diminished plasma protein leakage from brain edema by 50%. Targeted LNP-mediated delivery of VEc mRNA to the vascular network presents a promising platform for treating clinically relevant conditions involving vascular disruption.

Peritumoral brain edema (PBE) is common in intracranial meningiomas (IM) and has been linked to postoperative morbidity, yet its impact on cortical oxygenation remains unclear. We investigated the association between PBE and local tissue oxygenation using intraoperative in vivo hyperspectral imaging (HSI). Twenty-nine patients undergoing microsurgical IM resection with intraoperative HSI were prospectively analyzed. Peritumoral cortical oxygen saturation (StO2) was quantified and correlated with preoperative MRI parameters, including edema volume and contrast-enhancement intensity. Patients were stratified by PBE presence and histopathological subtype (meningotheliomatous vs nonmeningotheliomatous). Group comparisons used t-tests; correlations used Pearson coefficients. PBE was present in 17 (58.6%) cases. Patients with PBE exhibited significantly lower cortical oxygenation than those without (mean StO2 0.49 ± 0.13 vs 0.59 ± 0.10, P = .048). Within the PBE group, edema volume correlated positively with StO2 (r = 0.58, P = .015), whereas tumor contrast enhancement intensity correlated inversely with StO2 (r = -0.59, P = .013). No significant correlation was observed in patients without PBE (r = -0.26, P = .18). Meningotheliomatous IMs showed a trend toward lower StO2 compared with nonmeningotheliomatous tumors (0.51 ± 0.17 vs 0.55 ± 0.07, P = .05). PBE in IMs is associated with impaired cortical oxygenation. Larger PBEs paradoxically showed higher StO2, suggesting compensatory mechanisms, while strong tumor enhancement correlated with local hypoxia. These findings suggest that intraoperative HSI may serve as a promising tool for characterizing tumor-brain interactions and support further investigation into PBE pathophysiology.

As the principal active ingredient of Scutellaria baicalensis Georgi, Baicalin demonstrates anti-inflammatory and neuroprotective activities with the potential to repair brain injury. Nonetheless, poor solubility in water and low bioavailability of Ba limits its clinical application. To enhance solubility, bioavailability, and lesion-site delivery of Ba to reactive oxygen species (ROS)-rich lesions, we developed a ROS-responsive liposomal delivery system using DSPE-SS-PEG. Thin-film hydration was utilized to prepare the Ba-loaded liposomes (Ba@DSPE-SS-PEG-Liposome), before optimization via response surface methodology. The liposomes were comprehensively characterized in vitro using drug loading, particle size, morphology, release behavior, and encapsulation efficiency. Under high ROS conditions, internalization of ROS-responsive (DSPE-SS-PEG-modified) formulation was improved based on findings of cellular uptake studies. At the ischemic site, liposomes promoted targeted accumulation and prolonged systemic circulation of the drug. Neurological deficits, cerebral edema, and neuronal apoptosis were significantly alleviated in a rat model of hemorrhagic stroke by the ROS-responsive liposomes, which outperformed conventional liposomes and free Ba. Synergistic regulation of inflammatory and oxidative stress pathways mediated these therapeutic benefits. Altogether, the therapeutic efficacy of BA in hemorrhagic stroke can be effectively enhanced by this ROS-responsive (stimuli-responsive) liposomal system.

Tranexamic acid (TXA) may reduce the progression of vasogenic edema in traumatic brain injury (TBI), potentially providing a survival benefit in specific patients. This study evaluates a CT-based quantitative imaging tool for identifying patients with acute TBI who may benefit from prehospital TXA. This is a post hoc analysis of the Prehospital Tranexamic Acid Use for Traumatic Brain Injury trial, a multicenter, placebo-controlled trial that randomized patients with moderate or severe TBI to either a 1-g TXA bolus followed by 1-g infusion, a 2-g TXA bolus, or a placebo. CT images were analyzed using a novel Matlab-based algorithm to calculate the percentage of voxels within various density ranges. The region of interest was defined as the entire brain parenchyma after skull removal. The 10-20 HU range, identified as most representative of vasogenic edema based on correlation with mean ADC values in a subset of 102 patients, was used for further analysis. Logistic regression was performed to evaluate the relationship between voxel percentages in the 10-20 HU range and in-hospital mortality. Threshold analysis identified the minimum voxel percentage within the 10-20 HU range associated with significant TXA survival benefit. Relative risk reduction in mortality was calculated for patients above and below this threshold. In a cohort of 550 patients, logistic regression showed that the association between TXA use and in-hospital survival varied with the percentage of brain voxels in the 10-20 HU range (interaction P = .04). Threshold analysis identified a cutoff of 3% of brain parenchymal voxels in the 10-20 HU range, corresponding to approximately 40 mL of vasogenic edema, beyond which TXA administration was associated with a significant survival benefit (P = .04). In this subgroup, TXA was associated with a relative risk of mortality of 0.41 (95% CI, 0.17-0.99) compared with a placebo. A voxel percentage of ≥3% within the 10-20 HU CT density range serves as a promising imaging biomarker associated with a survival benefit from TXA in patients with acute TBI in the prehospital setting. Prospective validation is required to confirm these findings before integrating this biomarker into clinical decision-making for personalized TBI management.

Objective The research aimed to explore the protective effect of Nodakenin against cerebral ischemia–reperfusion (I/R) injury and its underlying mechanism, with a particular focus on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappa B (NF-κB) signaling axis, neuroinflammation, oxidative stress and ferroptosis. Methods The function of Nodakenin was investigated in a rat middle cerebral artery occlusion and reperfusion (MCAO/R) model and a PC12 cell oxygen–glucose deprivation and reoxygenation (OGD/R) model. Infarct size was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, brain edema was quantified using the wet–dry weight method, and histological changes were examined by hematoxylin and eosin (HE) staining. Biochemical assays and Western blotting was detected by malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6), along with PI3K/AKT–NF-κB pathway activity. Results Nodakenin treatment reduced infarct volume, histological damage and brain edema in cerebral I/R models. Nodakenin treatment suppressed proinflammatory cytokines, decreased MDA, restored SOD activity and attenuated ferroptosis-related alterations including Fe2+ accumulation and downregulation of GPX4 and FTH1. Consistent effects were observed in PC12 cells subjected to OGD/R. Mechanistically, Nodakenin activated the PI3K/AKT signaling pathway but suppressed NF-κB activation. These protective effects were abolished by PI3K inhibitor LY294002. Conclusion Nodakenin exerted neuroprotective effects against cerebral I/R injury by regulating the PI3K/AKT/NF-κB pathway to reduce neuroinflammation, oxidative stress and ferroptosis. These findings identify Nodakenin as a promising candidate for limiting secondary injury after ischemic stroke.

To evaluate the prevalence, patterns, and associations of retinal hemorrhages (RH) and intracranial hemorrhages (ICH) in confirmed abusive head trauma (AHT) cases, with attention to instances in which RH is identified without radiographic evidence of ICH. The authors retrospectively reviewed 137 confirmed AHT cases in children younger than 36 months treated between 2017 and 2023. Data included demographics, imaging results, skeletal surveys, and ophthalmologic examinations. Logistic regression analyses were used to identify predictors of RH and assess associations with ICH and clinical outcomes. ICH was present in 87.6% of cases, most commonly subdural hemorrhage (76.6%). RH was identified in 63.5% of cases, including 3 (3/137, 2.2%) without visible ICH on computed tomography, all of which demonstrated marked cerebral edema that may have obscured underlying hemorrhage. Subdural hemorrhage (odds ratio [OR]: 4.90, 95% CI: 1.83 to 13.16, P = .001) and subarachnoid hemorrhage (OR: 3.73, 95% CI: 1.32 to 10.52, P = .011) were independent predictors of RH, whereas abnormal skeletal survey (OR: 0.33, 95% CI: 0.14 to 0.77, P = .010) and mention of injuries in the chief complaint (OR: 0.31, 95% CI: 0.12 to 0.79, P = .014) were inversely associated. RH was significantly more likely in children older than 4 months (OR: 3.85, 95% CI: 1.50 to 9.87, P = .005) and was associated with increased mortality (26.4% vs 4.0%, P < .001). RH may occur in rare AHT cases without visible ICH, potentially due to masking by cerebral edema, supporting their continued role in clinical evaluation. The inverse association between RH and skeletal trauma suggests differing injury mechanisms, warranting further investigation.

Glibenclamide Attenuates Brain Edema After Intracerebral Hemorrhage Through Preservation of Blood-Brain Barrier Integrity and Glymphatic Function.

Acute liver failure (ALF) is a devastating condition that primarily affects young adults. This often-lethal condition involves a rapid loss of hepatic function, that then leads to multiple organ failure. The accumulation of numerous toxins, especially ammonia, causes cerebral oedema and intracranial hypertension. Continuous renal replacement therapy (CRRT) is increasingly recognized as having a key role in ammonia removal in ALF and current evidence suggesting that timing of initiation, dose, and duration of therapy may influence survival. In addition to this important role of toxin clearance, CRRT helps with other complications of ALF such as acid-base balance, prevention of fever and management of fluid balance. As such, we propose that CRRT in ALF should be viewed as an “metabolic-toxin-fluid” therapy as much as a treatment for renal failure. In this review article we will explore the mechanisms of benefit, indications and evidence to support this concept of CRRT in ALF.

Ferroptosis mechanisms in early brain injury after subarachnoid hemorrhage.

IGFBP7 protects against endothelial apoptosis and blood-brain barrier disruption following oxygen-glucose deprivation/reoxygenation.

White matter microstructure and cognitive decline in subacute ischemic stroke: Insights from free water imaging and glymphatic dysfunction.

Background/Objectives: Posterior reversible encephalopathy syndrome (PRES) is a neurological condition characterized by acute neurological symptoms and vasogenic edema, usually affecting the posterior circulation. It is described in end-stage renal disease (ESRD), but its presentation in peritoneal dialysis (PD) is not well defined. We aimed to describe the clinical, radiological, and dialysis-related features of PRES in PD patients and highlight factors relevant for diagnosis and management. Materials and Methods: We conducted a retrospective descriptive case series of four ESRD patients on PD or recently transitioned from PD to hemodialysis (HD) who developed PRES at a single center. Clinical data, laboratory results, dialysis characteristics, and neuroimaging findings were obtained from medical records. PRES was diagnosed based on acute neurological symptoms in the setting of severe hypertension and uremia, with CT and/or MRI findings supportive of PRES when present and exclusion of alternative diagnoses. Results: All patients presented with acute neurological manifestations, including headache, visual disturbances, seizures, and/or altered consciousness, in the context of marked hypertension and uremia. Neuroimaging findings ranged from normal CT/MRI to subtle bilateral occipital hypodensities and, in one case, extensive supra- and infratentorial vasogenic edema with internal hydrocephalus and subependymal edema. In three patients, inadequate volume or solute control on PD prompted temporary or permanent transition to HD to improve blood pressure and fluid management. With antihypertensive therapy, seizure control when required, correction of metabolic disturbances, and optimization of dialysis, all patients recovered clinically, with time to PRES resolution ranging from 7 to 43 days. Conclusions: PRES should be considered in PD patients with new-onset seizures, visual symptoms, or unexplained changes in mental status, particularly during hypertensive crises and uremia. Early CT/MRI, prompt blood pressure control, and careful adjustment of dialysis modality appear important for achieving favorable neurological outcomes.