Efficacy and safety of compound porcine cerebroside and ganglioside injection (CPCGI) versus piracetam on cognition and functional outcomes for adults with traumatic brain injury: A study protocol for randomized controlled trial.

Background: Traumatic brain injury (TBI) is a common neurosurgical disease in emergency rooms with poor prognosis, imposing severe burdens on patients and their families. Evidence indicates that piracetam and compound porcine cerebroside and ganglioside injection (CPCGI) can improve cognitive levels in TBI patients to enhance functional prognosis, but there is still a research gap regarding the efficacy of CPCGI. This study aims to determine the effectiveness and safety of CPCGI in improving cognitive and functional outcomes in TBI patients. Methods: This study is a multicenter, randomized, parallel-group, double-blind trial aiming to recruit 900 adult patients with mild to moderate TBI. After providing informed consent, 600 patients will be randomly assigned to the CPCGI group (20 ml/d, for 14 days), and 300 patients will be randomized to the piracetam group as a control (20 ml/d, for 14 days), followed up for 3 months after treatment. The primary outcome is the change in the Montreal Cognitive Assessment (MoCA) score from baseline after 3 months. The main secondary outcome measures include Mini-Mental State Examination (MMSE) scores, Glasgow Outcome Scale-Extended (GOS-E), and the Barthel Index at 1 and 3 months. Discussion: This multi-center clinical trial aims to provide high-quality evidence on the efficacy and safety of CPCGI in improving cognitive and functional outcomes in mild to moderate TBI patients. Trial registration: ChiCTR2000040466, date of registration: November 28, 2020.

The pharmacological landscape of chronic subdural hematoma: a systematic review and network meta-analysis of randomized and non-randomized controlled studies.

Background: There are various treatment modalities for chronic subdural hematoma (CSDH) and there is extensive debate surrounding pharmaceutical interventions. There is no consensus regarding the relative efficacy and safety of multiple treatment modalities. This study aims to investigate this issue and offer potential clinical recommendations. Methods: We searched PubMed, Web of Science, Embase and the Cochrane Library from January 2000 to May 2023 to identify randomized and nonrandomized controlled studies reporting one or more outcomes associated with the pharmacologic management of CSDH. The primary outcomes of interest included recurrence, favorable prognosis and adverse events, while the secondary outcomes included a reduction in hematoma volume and mortality. Pooled estimates, credible intervals and odds ratios were calculated for all outcomes using a fixed effects model. Confidence in network meta-analysis judgments were employed to stratify the evidential quality. This study was registered with PROSPERO: CRD42023406599. Results: The search strategy yielded 656 references; ultimately, 36 studies involving 8082 patients fulfilled our predefined inclusion criteria. The findings suggested that statins + glucocorticoids (GCs) ranked highest for preventing recurrence, improving prognosis and facilitating hematoma absorption. Tranexamic acid ranked second highest for preventing recurrence. Statins were found to be the preferred drug intervention for decreasing mortality and preventing adverse events. Antithrombotic agents ranked lowest in terms of decreasing mortality and improving prognosis. Conclusions: Our findings indicate that statins + GCs may be the most effective treatment modality for preventing recurrence, improving patient prognosis and facilitating hematoma absorption. In terms of reducing mortality and preventing adverse events, statins may be superior to other pharmacological interventions. Routine use of GCs is not suggested for patients with CSDH. Further prospective research is needed to directly compare the efficacy and superiority of various pharmaceutical interventions targeting CSDH to reinforce and validate our findings.

Cerebral microbleeds in patients with COVID-19: is there an inevitable connection?

The COVID-19 pandemic has underscored the critical interplay between systemic infections and neurological complications, notably cerebral microbleeds. This comprehensive review meticulously aggregates and analyses current evidence on cerebral microbleeds' prevalence, pathophysiological underpinnings and clinical implications within COVID-19 cohorts. Our findings reveal a pronounced correlation between cerebral microbleeds and increased severity of COVID-19, emphasizing the role of direct viral effects, inflammatory responses and coagulation disturbances. The documented association between cerebral microbleeds and elevated risks of morbidity and mortality necessitates enhanced neurological surveillance in managing COVID-19 patients. Although variability in study methodologies presents challenges, the cumulative evidence substantiates cerebral microbleeds as a critical illness manifestation rather than mere coincidence. This review calls for harmonization in research methodologies to refine our understanding and guide targeted interventions. Prioritizing the detection and study of neurological outcomes, such as cerebral microbleeds, is imperative for bolstering pandemic response strategies and mitigating the long-term neurological impact on survivors.

Association Between Prior Antiplatelet Therapy and Prognosis in Patients With Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

PURPOSE: Approximately 20% to 30% of intracerebral hemorrhage (ICH) patients were reported to be on antiplatelet therapy (APT), and association between prior APT and prognosis was unclear. We aimed to clarify the impact of APT on the prognosis of ICH through an updated systematic review and meta-analysis, and to further compare the risk of single APT (SAPT) or dual APT (DAPT) prior to ICH as well as the risk associated with various antiplatelet drugs. METHODS: EMBASE, MEDLINE via Ovid SP and Web of Science were searched from inception of each database to November 4, 2023. Included studies reported prognosis in both patients with prior APT and those without. FINDINGS: A total of 433,103 patients from 43 studies were included in the meta-analysis. Both univariate and multivariate analyses demonstrated a significant association between prior-APT and an increased mortality risk (odd ratio [OR] 1.43, 95% confidence interval [CI] 1.28-1.59; OR 1.20, 95%CI 1.10-1.30, respectively). The risk was higher in short term follow-up (Univariate OR 1.73, 95%CI 1.22-2.46; Multivariate OR 1.94, 95%CI 1.48-2.55). A notably increased risk of hematoma expansion was also observed in patients previously treated with APT (Univariate OR 1.47, 95%CI 1.12-1.94; Multivariate OR 1.88, 95%CI 1.30-2.71), which were mainly attributed to events within 24 hours. The impact of prior-APT on poor functional outcome was inconsistent between univariate and multivariate analyses. Both direct and indirect comparisons showed that SAPT significantly reduced the risk of mortality (OR 0.67, 95%CI 0.64-0.70; OR 0.84, 95%CI 0.71-0.99) and poor functional outcome (OR 0.84, 95%CI 0.72-0.98; OR 0.81, 95%CI 0.72-0.91) compared to DAPT. IMPLICATIONS: Prior-APT increased the risk of mortality and hematoma expansion in patients with ICH. The increased risk of mortality and hematoma expansion was more obvious in the short term follow-up and within 24 hours, respectively. The effect of APT on poor functional outcome exhibited inconsistency between univariate and multivariate analyses, suggesting that further investigation is warranted to clarify this relationship. In comparison with DAPT, SAPT could decrease the risk of mortality and poor functional outcome. Further studies focusing on antiplatelet drug response, racial differences, and specific APT regimens may help verify the influence.

Characteristics, predictors and outcomes of early postoperative cerebral infarction on computed tomography in spontaneous intracerebral hemorrhage.

Early postoperative cerebral infarction (ePCI) is a serious complication of spontaneous intracerebral hemorrhage (SICH). Yet, no study has specifically focused on ePCI among SICH patients. Our study aims to investigate the characteristics, predictors, and outcomes of ePCI observed on computed tomography (CT) within 72 h after surgery in patients with supratentorial SICH. Data from a single-center SICH study conducted from May 2015 to September 2022 were retrospectively analyzed. We described the characteristics of ePCI. Predictors were identified through logistic regression analysis, and the impact of ePCI on six-month mortality was examined using a Cox regression model. Subgroup analyses and the "E-value" approach assessed the robustness of the association between ePCI and mortality. A retrospective analysis of 637 out of 3938 SICH patients found that 71 cases (11.1%) developed ePCI. The majority of ePCI cases occurred on the bleeding side (40/71, 56.3%) and affected the middle cerebral artery (MCA) territory (45/71, 63.4%). Multivariable analysis showed that the Glasgow Coma Scale (GCS) score (odds ratio (OR), 0.62; 95% CI, 0.48-0.8; p < 0.001), bleeding volume (per 100 ml) (OR, 1.17; 95% CI, 1.03-1.32; p = 0.016), hematoma volume (per 10 ml) (OR, 1.14; 95%CI, 1.02-1.28; p = 0.023) and bilateral brain hernia (OR, 6.48; 95%CI, 1.71-24.48; p = 0.006) independently predicted ePCI occurrence. ePCI was significantly associated with increased mortality (adjusted hazard ratio (HR), 3.6; 95% CI, 2.2-5.88; p < 0.001). Subgroup analysis and E-value analysis (3.82-6.66) confirmed the stability of the association. ePCI is a common complication of SICH and can be predicted by low GCS score, significant bleeding, large hematoma volume, and brain hernia. Given its significant increase in mortality, ePCI should be explored in future studies.

Effect of l-oxiracetam and oxiracetam on memory and cognitive impairment in mild-to-moderate traumatic brain injury patients: Study protocol for a randomized controlled trial.

Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam-like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of l-oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods: The study adopts a multicenter, randomized, double-blind, parallel-group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: l-oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow-up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion: There is no robust evidence to suggest that l-oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565.

Cisternostomy is not beneficial to reduce the occurrence of post-traumatic hydrocephalus in Traumatic Brain Injury.

BACKGROUND: The Cisternostomy is a novel surgical concept in the treatment of Traumatic Brain Injury (TBI), which can effectively drain the bloody cerebrospinal fluid from the skull base cistern, reduce the intracranial pressure, and improve the return of bone flap, but its preventive role in post-traumatic hydrocephalus (PTH) is unknow. The purpose of this paper is to investigate whether Cisternostomy prevents the occurrence of PTH in patients with moderate and severe TBI. METHODS: A retrospective analysis of clinical data of 86 patients with moderate and severe TBI from May 2019 to October 2021 was carried out in the Brain Trauma Center of Tianjin Huanhu Hospital. Univariate analysis was performed to examine the gender, age, preoperative Glasgow Coma Scale (GCS) score, preoperative Rotterdam CT score, decompressive craniectomy rate, intracranial infection rate, the incidence of subdural fluid, and incidence of hydrocephalus in patients between the Cisternostomy group and the non-Cisternostomy surgery group. we also analyzed the clinical outcome indicators like GCS at discharge,6 month GOS-E and GOS-E ≥ 5 in two groups.Additionaly, the preoperative GCS score, decompressive craniectomy rate, age, and gender of patients with PTH and non hydrocephalus were compared. Further multifactorial logistic binary regression was performed to explore the risk factors for PTH. Finally, we conducted ROC curve analysis on the statistically significant results from the univariate regression analysis to predict the ability of each risk factor to cause PTH. RESULTS: The Cisternostomy group had a lower bone flap removal rate(48.39% and 72.73%, p = 0.024)., higer GCS at discharge(11.13 ± 2.42 and 8.93 ± 3.31,p = 0.000) and better 6 month GOS-E(4.55 ± 1.26 and 3.95 ± 1.18, p = 0.029)than the non-Cisternostomy group However, there was no statistical difference in the incidence of hydrocephalus between the two groups (25.81% and 30.91%, p = 0.617). Moreover, between the hydrocephalus group and no hydrocephalus group,there were no significant differences in the incidence of gender, age, intracranial infection, and subdural fluid. While there were statistical differences in peroperative GCS score, Rotterdam CT score, decompressive craniectomy rate, intracranial infection rate, and the incidence of subdural fluid in the two groups, there was no statistical difference in the percentage of cerebral cisterns open drainage between the hydrocephalus group and no hydrocephalus group (32.00% and 37.70%, p = 0.617). Multifactorial logistic binary regression analysis results revealed that the independent risk factors for PTH were intracranial infection (OR = 18.460, 95% CI: 1.864-182.847 p = 0.013) and subdural effusion (OR = 10.557, 95% CI: 2.425-35.275 p = 0.001). Further, The ROC curve analysis showed that peroperative GCS score, Rotterdam CT score and subdural effusion had good ACU(0.785,0.730,and 0.749), with high sensitivity and specificity to predict the occurrence of PTH. CONCLUSIONS: Cisternostomy may decrease morbidities associated with removal of the bone flap and improve the clinical outcome, despite it cannot reduce the disability rate in TBI patients.Intracranial infection and subdural fluid were found to be the independent risk factors for PTH in patients with TBI,and the peroperative GCS score, Rotterdam CT score and subdural effusion had higher sensitivity and specificity to predict the occurrence of PTH. And more importantly, no correlation was observed between open drainage of the cerebral cisterns and the occurrence of PTH, indicating that Cisternostomy may not be beneficial in preventing the occurrence of PTH in patients with moderate and severe TBI.

Establishment and validation of a CT-based prediction model for the good dissolution of mild chronic subdural hematoma with atorvastatin treatment.

PURPOSE: To develop and validate a prediction model based on imaging data for the prognosis of mild chronic subdural hematoma undergoing atorvastatin treatment. METHODS: We developed the prediction model utilizing data from patients diagnosed with CSDH between February 2019 and November 2021. Demographic characteristics, medical history, and hematoma characteristics in non-contrast computed tomography (NCCT) were extracted upon admission to the hospital. To reduce data dimensionality, a backward stepwise regression model was implemented to build a prognostic prediction model. We calculated the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model by a tenfold cross-validation procedure. RESULTS: Maximum thickness, volume, mean density, morphology, and kurtosis of the hematoma were identified as the most significant predictors of good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The prediction model exhibited good discrimination, with an area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.74-0.90) and good calibration (p = 0.613). The validation analysis showed the AUC of the final prognostic prediction model is 0.80 (95% CI 0.71-0.86) and it has good prediction performance. CONCLUSION: The imaging data-based prediction model has demonstrated great prediction accuracy for good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The study results emphasize the importance of imaging data evaluation in the management of CSDH patients.

Exploring the causal role of immune cells in cerebral aneurysm through single-cell transcriptomics and Mendelian randomization analysis.

Cerebral aneurysm (CA) represents a significant clinical challenge, characterized by pathological dilation of cerebral arteries. Recent evidence underscores the crucial involvement of immune cells in CA pathogenesis. This study aims to explore the complex interplay between immune cells and CA formation. We analyzed single-cell RNA sequencing data from the GSE193533 dataset, focusing on unruptured CA and their controls. Comprehensive cell-type identification and pseudo-time trajectory analyses were conducted to delineate the dynamic shifts in immune cell populations. Additionally, a two-sample Mendelian randomization (MR) approach was employed to investigate the causal influence of various immunophenotypes on CA susceptibility and the reciprocal effect of CA formation on immune phenotypes. Single-cell transcriptomic analysis revealed a progressive loss of vascular smooth muscle cells (VSMCs) and an increase in monocytes/macrophages (Mo/MΦ) and other immune cells, signifying a shift from a structural to an inflammatory milieu in CA evolution. MR analysis identified some vital immunophenotypes, such as CD64 on CD14+ CD16+ monocytes (OR: 1.236, 95% CI: 1.064-1.435, P = 0.006), as potential risk factors for CA development, while others, like CD28- CD8br %CD8br (OR: 0.883, 95% CI: 0.789-0.988, P = 0.030), appeared protective. Reverse MR analysis demonstrated that CA formation could modulate specific immunophenotypic expressions, highlighting a complex bidirectional interaction between CA pathology and immune response. This study underscores the pivotal role of immune cells in this process through the integration of single-cell transcriptomics with MR analysis, offering a comprehensive perspective on CA pathogenesis, and potentially guiding future therapeutic strategies targeting specific immune pathways.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Cannabidiol Alleviates Neurological Deficits After Traumatic Brain Injury by Improving Intracranial Lymphatic Drainage.

Traumatic brain injury (TBI) persists as a substantial clinical dilemma, largely because of the absence of effective treatments. This challenge is exacerbated by the hindered clearance of intracranial metabolic byproducts and the continual accrual of deleterious proteins. The glymphatic system (GS) and meningeal lymphatic vessels (MLVs), key elements of the intracranial lymphatic network, play critical roles in the clearance of harmful substances. Cannabidiol (CBD) has shown promise in reducing metabolite overload and bolstering cognitive performance in various neurodegenerative diseases. The precise mechanisms attributing to its beneficial effects in TBI scenarios, however, are yet to be distinctly understood. Utilizing a fluid percussion injury paradigm, our research adopted a multifaceted approach, encompassing behavioral testing, immunofluorescence and immunohistochemical analyses, laser speckle imaging, western blot techniques, and bilateral cervical efferent lymphatic ligation. This methodology aimed to discern the influence of CBD on both neurological outcomes and intracranial lymphatic clearance in a murine TBI model. We observed that CBD administration notably ameliorated motor, memory, and cognitive functions, concurrently with a significant reduction in the concentration of phosphorylated tau protein and amyloid-ß. In addition, CBD expedited the turnover and elimination of intracranial tracers, increased cerebral blood flow, and enhanced the efficacy of fluorescent tracer migration from MLVs to deep cervical lymph nodes (dCLNs). Remarkably, CBD treatment also induced a reversion in aquaporin-4 (AQP-4) polarization and curtailed neuroinflammatory indices. A pivotal discovery was that the surgical interruption of efferent lymphatic conduits in the neck nullified CBD's positive contributions to intracranial waste disposal and cognitive improvement, yet the anti-neuroinflammatory actions remained unaffected. These insights suggest that CBD may enhance intracranial metabolite clearance, potentially via the regulation of the intracranial lymphatic system, thereby offering neurofunctional prognostic improvement in TBI models. Our findings underscore the potential therapeutic applicability of CBD in TBI interventions, necessitating further comprehensive investigations and clinical validations to substantiate these initial conclusions.

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.

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system.

BACKGROUND: Diffuse brain injury (DBI) models are characterized by intense global brain inflammation and edema, which characterize the most severe form of TBI. In a previous experiment, we found that fingolimod promoted recovery after controlled cortical impact injury (CCI) by modulating inflammation around brain lesions. However, it remains unclear whether fingolimod can also attenuate DBI because of its different injury mechanisms. Furthermore, whether fingolimod has additional underlying effects on repairing DBI is unknown. METHODS: The impact acceleration model of DBI was established in adult Sprague-Dawley rats. Fingolimod (0.5 mg/kg) was administered 0.5, 24, and 48 h after injury for 3 consecutive days. Immunohistochemistry, immunofluorescence analysis, cytokine array, and western blotting were used to evaluate inflammatory cells, inflammatory factors, AQP4 polarization, apoptosis in brain cells, and the accumulation of APP after DBI in rats. To evaluate the function of the glymphatic system (GS), a fluorescent tracer was injected into the cistern. The neural function of rats with DBI was evaluated using various tests, including the modified neurological severity score (mNSS), horizontal ladder-crossing test, beam walking test, and tape sensing and removal test. Brain water content was also measured. RESULTS: Fingolimod administration for 3 consecutive days could reduce the levels of inflammatory cytokines, neutrophil recruitment, microglia, and astrocyte activation in the brain following DBI. Moreover, fingolimod reduced apoptotic protein expression, brain cell apoptosis, brain edema, and APP accumulation. Additionally, fingolimod inhibited the loss of AQP4 polarization, improved lymphatic system function, and reduced damage to nervous system function. Notably, inhibiting the GS weakened the therapeutic effect of fingolimod on the neurological function of rats with DBI and increased the accumulation of APP in the brain. CONCLUSIONS: In brief, these findings suggest that fingolimod alleviates whole-brain inflammation and GS system damage after DBI and that inhibiting the GS could weaken the positive effect of fingolimod on nerve function in rats with DBI. Thus, inhibiting inflammation and regulating the GS may be critical for the therapeutic effect of fingolimod on DBI.

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.

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.

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.

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.

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.