Cognitive impairment in Chinese traumatic brain injury patients: from challenge to future perspectives.

Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients.

Cannabidiol alleviates neurological deficits after traumatic brain injury by improving intracranial lymphatic drainage.

Traumatic brain injury (TBI)-a severe clinical problem-is compounded by a lack of effective treatments and impeded intracranial metabolic waste clearance. The glymphatic system and meningeal lymphatic vessels are instrumental in TBI pathophysiology and crucial for clearing harmful substances. Cannabidiol (CBD) has the potential to address metabolic imbalances and improve cognitive functions in neurodegenerative diseases, but its specific effect on TBI remains unclear. Using a fluid percussion injury model, we adopted a comprehensive approach that included behavioral testing, various imaging techniques, and deep cervical lymph node (dCLN) ligation to evaluate CBD's effects on neurological outcomes and lymphatic clearance in a TBI mouse model. Our results demonstrated that CBD markedly enhanced motor, memory, and cognitive functions, correlating with reduced levels of detrimental neural proteins. CBD also expedited the removal of intracranial tracers, increased cerebral blood flow, and improved tracer migration from lymphatic vessels to dCLNs. Intriguingly, CBD treatment modified aquaporin-4 polarization and diminished neuroinflammatory indicators. A key observation was that disrupting efferent lymphatic channels nullified CBD's positive effects on waste removal and cognitive enhancements, whereas its anti-inflammatory benefits continued. This finding suggests that CBD's ability to improve waste clearance may operate via the lymphatic system, thereby improving neurological outcomes in TBI patients. Therefore, our study underscores CBD's potential therapeutic role in TBI management.

Lymph-targeted high-density lipoprotein-mimetic nanovaccine for multi-antigenic personalized cancer immunotherapy.

Cancer vaccines show huge potential for cancer prevention and treatment. However, their efficacy remains limited due to weak immunogenicity regarding inefficient stimulation of cytotoxic T lymphocyte (CTL) responses. Inspired by the unique characteristic and biological function of high-density lipoprotein (HDL), we here develop an HDL-mimicking nanovaccine with the commendable lymph-targeted capacity to potently elicit antitumor immunity using lipid nanoparticle that is co-loaded with specific cancer cytomembrane harboring a collection of tumor-associated antigens and an immune adjuvant. The nanoparticulate impact is explored on the efficiency of lymphatic targeting and dendritic cell uptake. The optimized nanovaccine promotes the co-delivery of antigens and adjuvants to lymph nodes and maintains antigen presentation of dendritic cells, resulting in long-term immune surveillance as the elevated frequency of CTLs within lymphoid organs and tumor tissue. Immunization of nanovaccine suppresses tumor formation and growth and augments the therapeutic efficacy of checkpoint inhibitors notably on the high-stemness melanoma in the mouse models.

CD4+ CD11b+ T cells infiltrate and aggravate the traumatic brain injury depending on brain-to-cervical lymph node signaling.

AIM: We aim to identify the specific CD4+ T-cell subtype influenced by brain-to-CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). METHOD: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T-cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b-positive CD4+ T cells, within the affected region. The population of CD4+ CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. Administration of CD4+ CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. CONCLUSION: The infiltration of CD4+ CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain-to-CLN signaling.

Development and comprehensive SBSE-GC/Q-TOF-MS analysis optimization, comparison, and evaluation of different mulberry varieties volatile flavor.

Optimization of seven parameters of stir bar sorptive extraction (SBSE) on mulberry volatile components for the first time. A total of 347 volatile components were identified and quantified in 14 mulberry varieties, predominantly encompassing esters, aldehydes, terpenoids, hydrocarbons, ketones, alcohols, heterocyclics, acids, and phenols. Hexanal and (E)-2-hexenal were the dominant volatiles. Furthermore, 79 volatile compounds characterized by odor activity values (OAVs) > 1 were identified, making a significant contribution to the distinctive mulberry flavor. "Green" notes were the most intense, followed by "fatty" and "fruity". Utilizing odor ring charts, the volatile flavor characteristics of the 14 mulberry varieties could be intuitively distinguished. This study not only established a viable methodology for differentiating mulberry varieties but also laid a theoretical foundation for the quality evaluation and variety breeding of mulberry flavor.

The value of computed tomography texture analysis in identifying chronic subdural hematoma patients with a good response to polytherapy.

This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.

A rumen-derived bifunctional glucanase/mannanase uncanonically releases oligosaccharides with a high degree of polymerization preferentially from branched substrates.

Glycoside hydrolases (GHs) are known to depolymerize polysaccharides into oligo-/mono-saccharides, they are extensively used as additives for both animals feed and our food. Here we reported the characterization of IDSGH5-14(CD), a weakly-acidic mesophilic bifunctional mannanase/glucanase of GH5, originally isolated from sheep rumen microbes. Biochemical characterization studies revealed that IDSGH5-14(CD) exhibited preferential hydrolysis of mannan-like and glucan-like substrates. Interestingly, the enzyme exhibited significantly robust catalytic activity towards branched-substrates compared to linear polysaccharides (P < 0.05). Substrate hydrolysis pattern indicated that IDSGH5-14(CD) predominantly liberated oligosaccharides with a degree of polymerization (DP) of 3-7 as the end products, dramatically distinct from canonical endo-acting enzymes. Comparative modeling revealed that IDSGH5-14(CD) was mainly comprised of a (ß/α)8-barrel-like structure with a spacious catalytic cleft on surface, facilitating the enzyme to target high-DP or branched oligosaccharides. Molecular dynamics (MD) simulations further suggested that the branched-ligand, 64-α-D-galactosyl-mannohexose, was steadily accommodated within the catalytic pocket via a two-sided clamp formed by the aromatic residues. This study first reports a bifunctional GH5 enzyme that predominantly generates high-DP oligosaccharides, preferentially from branched-substrates. This provides novel insights into the catalytic mechanism and molecular underpinnings of polysaccharide depolymerization, with potential implications for feed additive development and high-DP oligosaccharides preparation.

Delayed Administration of an Angiotensin II Type 2 Receptor Agonist Promotes Functional Recovery of the Brain and Heart After Traumatic Brain Injury.

Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). TBI was induced by cortical impact injury in male adult C57BL/6J mice, and the mice received C21 (0.03 mg/kg, intraperitoneally) starting from 24 h after TBI and continuing once daily. C21 facilitated cognitive function recovery until 1 month after TBI. C21 alleviated blood-brain barrier leakage and brain edema and inhibited the expression of proinflammatory cytokines in the brain after 3 consecutive days of treatment. C21 improved cerebral blood flow after 1 month, although the lesion volume was not affected. C21 also reduced the expression of proinflammatory cytokines in the heart after a 3-day consecutive treatment. Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.

Inactivation of ERK1/2 signaling mediates dysfunction of basal meningeal lymphatic vessels in experimental subdural hematoma.

Rationale: Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis remains unclear. Herein, we aimed to understand the pathological mechanisms of MLV dysfunction following SDH and to test whether atorvastatin, an effective drug for SDH clearance, improves meningeal lymphatic drainage (MLD). Methods: We induced SDH models in rats by injecting autologous blood into the subdural space and evaluated MLD using Gadopentetate D, Evans blue, and CFSE-labeled erythrocytes. Whole-mount immunofluorescence and transmission electron microscopy were utilized to detect the morphology of MLVs. Phosphoproteomics, western blot, flow cytometry, and in vitro experiments were performed to investigate the molecular mechanisms underlying dysfunctional MLVs. Results: The basal MLVs were detected to have abundant valves and play an important role in draining subdural substances. Following SDH, these basal MLVs exhibited disrupted endothelial junctions and dilated lumen, leading to impaired MLD. Subsequent proteomics analysis of the meninges detected numerous dephosphorylated proteins, primarily enriched in the adherens junction, including significant dephosphorylation of ERK1/2 within the meningeal lymphatic endothelial cells (LECs). Subdural injection of the ERK1/2 kinase inhibitor PD98059 resulted in dilated basal MLVs and impaired MLD, resembling the dysfunctional MLVs observed in SDH. Moreover, inhibiting ERK1/2 signaling severely disrupted intercellular junctions between cultured LECs. Finally, atorvastatin was revealed to protect the structure of basal MLVs and accelerate MLD following SDH. However, these beneficial effects of atorvastatin were abolished when combined with PD98059. Conclusion: Our findings demonstrate that SDH induces ERK1/2 dephosphorylation in meningeal LECs, leading to disrupted basal MLVs and impaired MLD. Additionally, we reveal a beneficial effect of atorvastatin in improving MLD.

Multimodality management for chronic subdural hematoma in China: protocol and characteristics of an ambidirectional, nationwide, multicenter registry study.

BACKGROUND: Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population. METHODS/DESIGN: A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up. RESULT: Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%. CONCLUSION: This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition. TRIAL REGISTRATION: ChiCTR2200057179.

Vitamin D accelerates the subdural hematoma clearance through improving the meningeal lymphatic vessel function.

Subdural hematoma (SDH) drains into the extracranial lymphatic system through the meningeal lymphatic vessels (mLVs) but the formation of SDH impairs mLVs. Because vitamin D (Vit D) can protect the endothelial cells, we hypothesized that Vit D may enhance the SDH clearance. SDH was induced in Sprague-Dawley rats and treated with Vit D or vehicle. Hematoma volume in each group was measured by H&E staining and hemoglobin quantification. Evans blue (EB) quantification and red blood cells injection were used to evaluated the drainage of mLVs. Western blot analysis and immunofluorescence were conducted to assess the expression of lymphatic protein markers. We also examined the inflammatory factors levels in subdural space by ELISA. Vit D treatment significantly reduced SDH volume and improved the drainage of SDH to cervical lymph nodes. The structure of mLVs in SDH rats were protected by Vit D, and the expressions of LYVE1, PROX1, FOXC2, and VE-cadherin were increased after Vit D treatment. The TNF-α, IL-6, and IL-8 levels were reduced in Vit D group. In vitro, Vit D also increased the VE-cadherin expression levels under inflammation. Vit D protects the structure of mLVs and enhances the absorption of SDH, partly by the anti-inflammatory effect of Vit D.

Chinese Neurosurgical Randomized Controlled Trials: Dynamics in Trial Implementation and Completion.

BACKGROUND AND OBJECTIVES: The focus on evidence-based neurosurgery has led to a considerable amount of neurosurgical evidence based on randomized controlled trials (RCTs) being published. Nevertheless, there has been no systematic appraisal of China's contribution to RCTs. Information about the changes in characteristics of Chinese neurosurgical RCTs before and during the COVID-19 pandemic is limited. This study aims to perform a detailed examination and comprehensive analysis of the characteristics of Chinese neurosurgical RCTs and to examine the differences before and during the COVID-19 pandemic. METHODS: We conducted a comprehensive database search including PubMed, Web of Science, Embase, and Cochrane Library up to March 2023, with a criterion of inclusion based on an impact factor above 0. We subsequently examined the design and quality parameters of the included RCTs and assessed the differences before and during the COVID-19 pandemic (based on follow-up ending before or after January 2020). Moreover, we investigated potential factors that may affect the quality and developmental trends of neurosurgical RCTs in China. RESULTS: The main focus of the 91 neurosurgical RCTs was vascular disease (47.3%) and trauma (18.7%). Over half of the trials used Consolidated Standards of Reporting Trial diagrams (69.2%), and the majority compared nonsurgical treatments (63.7%). Larger trials tended to have better quality scores, but those with significant efficacy were less likely to have power calculations. Over time, there was an increase in the use of Consolidated Standards of Reporting Trial diagrams and well-specified outcomes. The COVID-19 pandemic may have hindered the completion of neurosurgical RCTs in China, but it has had little impact on the design and quality so far. CONCLUSION: Chinese neurosurgeons have made significant progress in advancing neurosurgical RCTs despite challenges. However, shortcomings in sample size and power calculation need attention. Improving the rigor, rationality, and completeness of neurosurgical RCT design is crucial.

Vertical tearing of subducting plates controlled by geometry and rheology of oceanic plates.

Lateral non-uniform subduction is impacted by continuous plate segmentation owing to vertical tearing of the subducting plate. However, the dynamics and physical controls of vertical tearing remain controversial. Here, we employed 3D numerical models to investigate the effects of trench geometry (offset by a transform boundary) and plate rheology (plate age and the magnitude of brittle/plastic strain weakening) on the evolution of shear stress-controlled vertical tearing within a homogenous subducting oceanic plate. Numerical results suggest that the trench offset geometry could result in self-sustained vertical tearing as a narrow shear zone within the intact subducting oceanic plate, and that this process of tearing could operate throughout the entire subduction process. Further, the critical trench offset length for the maturation of vertical tearing is impacted by plate rheology. Comparison between numerical modelling results and natural observations suggests that vertical tearing attributed to trench offset geometry is broadly developed in modern subduction and collision systems worldwide.

The fabrication of silicon/dual-network carbon nanofibers/carbon nanotubes as free-standing anodes for lithium-ion batteries.

Silicon, known for its high theoretical capacity and abundant resources, is regarded as one of the most promising anode materials for lithium-ion batteries (LIBs). However, the application of silicon anode materials is limited by huge expansion and poor electricity of silicon. Herein, a novel free-standing Si/C anode (noted as Si/CNFs/CNTs) is synthesized by combining electrospinning and in situ chemical vapor deposition, in which Si nanoparticles are composited with a conducting dual-network composed of carbon nanofibers (CNFs) and in situ deposited carbon nanotubes (CNTs). In situ deposited CNTs surround the surface of CNFs to form an elastic buffer layer on the surface of Si attached to CNFs, which ensures structural integrity. CNTs with excellent conductivity and a large specific surface area shorten Li+ transport pathways. Therefore, Si/CNFs/CNTs exhibits stable cycling performance and maintains a capacity of 639.9 mA h g-1 and a capacity retention rate of 69.9% after 100 cycles at a current density of 0.1 A g-1. This work provides a promising approach for the structural modification of self-supporting Si/C electrodes.

Differential patterns of very high-frequency oscillations in two seizure types of the pilocarpine-induced TLE model.

AIMS: Very high-frequency oscillations (VHFOs, >500 Hz) are considered a highly sensitive biomarker of seizures. We hypothesized that VHFOs may exhibit specificity towards hypersynchronous (HYP) seizures and low-voltage fast (LVF) seizures in temporal lobe epilepsy (TLE). METHODS: Local field potentials were recorded from the hippocampal network in TLE mice induced by pilocarpine. Subsequently, we analyzed the VHFO features, including their temporal-frequency characteristics and VHFO/theta coupling, during three states: baseline, preictal, and postictal for both HYP- and LVF-seizure groups. RESULTS: Significant changes in most of the VHFO features were observed during the preictal state in both seizure groups. In the postictal state, VHFO features in the HYP-seizure group exhibited inverse alterations and appeared to align with those observed during baseline conditions. However, such phenomena were not observed after TLE seizures in the LVF-seizure group. CONCLUSION: Our findings highlight distinct patterns of VHFO feature changes across different states of HYP seizures and LVF seizures. These results suggest that VHFOs could serve as indicative biomarkers for seizure alterations specifically associated with HYP-seizure states.

Nanomedicine strategies to counteract cancer stemness and chemoresistance.

Cancer stem-like cells (CSCs) identified by self-renewal ability and tumor-initiating potential are responsible for tumor recurrence and metastasis in many cancers. Conventional chemotherapy fails to eradicate CSCs that hold a state of dormancy and possess multi-drug resistance. Spurred by the progress of nanotechnology for drug delivery and biomedical applications, nanomedicine has been increasingly developed to tackle stemness-associated chemotherapeutic resistance for cancer therapy. This review focuses on advances in nanomedicine-mediated therapeutic strategies to overcome chemoresistance by specifically targeting CSCs, the combination of chemotherapeutics with chemopotentiators, and programmable controlled drug release. Perspectives from materials and formulations at the nano-scales are specifically surveyed. Future opportunities and challenges are also discussed.

Pb(II)-inducible proviolacein biosynthesis enables a dual-color biosensor toward environmental lead.

With the rapid development of synthetic biology, various whole-cell biosensors have been designed as valuable biological devices for the selective and sensitive detection of toxic heavy metals in environmental water. However, most proposed biosensors are based on fluorescent and bioluminescent signals invisible to the naked eye. The development of visible pigment-based biosensors can address this issue. The pbr operon from Klebsiella pneumoniae is selectively induced by bioavailable Pb(II). In the present study, the proviolacein biosynthetic gene cluster was transcriptionally fused to the pbr Pb(II) responsive element and introduced into Escherichia coli. The resultant biosensor responded to Pb(II) in a time- and dose-dependent manner. After a 5-h incubation with Pb(II), the brown pigment was produced, which could be extracted into n-butanol. Extra hydrogen peroxide treatment during n-butanol extract resulted in the generation of a stable green pigment. An increased brown signal was observed upon exposure to lead concentrations above 2.93 nM, and a linear regression was fitted from 2.93 to 3,000 nM. Extra oxidation significantly decreased the difference between parallel groups. The green signal responded to as low as 0.183 nM Pb(II), and a non-linear regression was fitted in a wide concentration range from 0.183 to 3,000 nM. The specific response toward Pb(II) was not interfered with by various metals except for Cd(II) and Hg(II). The PV-based biosensor was validated in monitoring bioaccessible Pb(II) spiked into environmental water. The complex matrices did not influence the regression relationship between spiked Pb(II) and the dual-color signals. Direct reading with the naked eye and colorimetric quantification enable the PV-based biosensor to be a dual-color and low-cost bioindicator for pollutant heavy metal.

Structure and Properties of Carboxylated Carbon Nanotubes@Expanded Graphite/Polyethersulfone Composite Bipolar Plates for PEM.

Composite bipolar plates (BPs) hinder their application in proton exchange membrane fuel cells (PEMFC) because of their poor conductivity and mechanical properties. Nanofillers can effectively solve this problem but often have a limited effect due to their easy agglomeration. In this work, a continuous mesh carboxylated multi-walled carbon nanotube (MWCNT) coating on the surface of graphite was synthesized by chemical vapor deposition (CVD) and carboxylation modification, and the composite BPs were prepared by molding using prepared reticulated carboxylated MWCNTs, expanded graphite, and resin. By optimizing the carboxylation treatment time and the content of the nano-filler, the composite BPs had the best performance at a 15 min carboxylation treatment time and 2.4% filler content. The planar conductivity reached up to 243.52 S/cm, while the flexural strength increased to 61.9 MPa. The thermal conductivity and hydrophobicity were improved compared with the conventional graphite/resin composite BPs, and good corrosion resistance has been demonstrated under the PEMFC operating environment. This work provides a novel nanofiller modification paradigm for PBs.

Improvements of the Tada formula in estimating the intracerebral hemorrhage volume based on computed tomography.

Background: The Tada formula has been used widely for assessing intracerebral hemorrhage (ICH) volume. However, it is only suitable for calculating regular and small volume hematomas. Therefore, we attempted to improve the formula to increase its accuracy and maintain its efficiency. Methods: Computed tomography (CT) data of 15 balls of different shapes filled with predetermined volumes of water were collected to verify the high accuracy of FireVoxel in measuring the volume. CT data from 329 patients with ICH from two different hospitals grouped by hematoma shape and volume were retrospectively reviewed. The distinctly shaped ICH volumes of 245 patients from one of the hospitals were estimated using FireVoxel and the Tada formula grouped by the hematoma shape and volume. Taking the hematoma volumes measured by FireVoxel as the reference standard, the accuracy and reliability of the Tada formula were evaluated. Polynomial fitting was employed to determine the associations of the values calculated between the Tada formula and FireVoxel. Then, a corrected Tada formula (C-Tada formula) was produced, and the limits of agreement between the C-Tada formula and Tada formula were analyzed with Bland-Altman analysis. The C-Tada formula was validated by the CT data of 84 patients from another hospital. Results: The volume measured by FireVoxel can be set as the reference standard. The ICH volume calculated by the Tada formula was significantly greater than that calculated by FireVoxel for different shapes and volumes. The percentage deviation between the volumes calculated by FireVoxel and the Tada formula was also statistically significant and influenced by ICH shape and volume. The limits of agreement between the C-Tada formula and FireVoxel were tighter than those between the Tada formula and FireVoxel. The percentage deviation of the C-Tada formula calculation from the FireVoxel estimate was greatly reduced relative to that for the Tada formula for each group. Conclusions: The C-Tada formula is more clinically valuable than the Tada formula, given its sufficient efficiency and greater accuracy and reliability in ICH volume calculation.

Cerebral glucagon-like peptide-1 receptor activation alleviates traumatic brain injury by glymphatic system regulation in mice.

AIM: We aimed to assess the effects of cerebral glucagon-like peptide-1 receptor (GLP-1R) activation on the glymphatic system and whether this effect was therapeutic for traumatic brain injury (TBI). METHODS: Immunofluorescence was employed to evaluate glymphatic system function. The blood-brain barrier (BBB) permeability, microvascular basement membrane, and tight junction expression were assessed using Evans blue extravasation, immunofluorescence, and western blot. Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis was evaluated using Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and western blot. Cognitive function was assessed using behavioral tests. RESULTS: Cerebral GLP-1R activation restored glymphatic transport following TBI, alleviating BBB disruption and neuronal apoptosis, thereby improving cognitive function following TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor TGN-020 abolished the protective effect of the GLP-1R agonist against cognitive impairment. CONCLUSION: Cerebral GLP-1R activation can effectively ameliorate neuropathological changes and cognitive impairment following TBI; the underlying mechanism could involve the repair of the glymphatic system damaged by TBI.