Integrating network pharmacology and transcriptomic omics reveals that akebia saponin D attenuates neutrophil extracellular traps-induced neuroinflammation via NTSR1/PKAc/PAD4 pathway after intracerebral hemorrhage.

Neutrophils and their production of neutrophil extracellular traps (NETs) significantly contribute to neuroinflammation and brain damage after intracerebral hemorrhage (ICH). Although Akebia saponin D (ASD) demonstrates strong anti-inflammatory activities and blood-brain barrier permeability, its role in regulating NETs formation and neuroinflammation following ICH is uncharted. Our research focused on unraveling the influence of ASD on neuroinflammation mediated by NETs and the mechanisms involved. We found that increased levels of peripheral blood neutrophils post-ICH are correlated with worse prognostic outcomes. Through network pharmacology, we identified ASD as a promising therapeutic target for ICH. ASD administration significantly improved neurobehavioral performance and decreased NETs production in neutrophils. Furthermore, ASD was shown to upregulate the membrane protein NTSR1 and activate the cAMP signaling pathway, confirmed through transcriptome sequencing, western blot, and immunofluorescence. Interestingly, the NTSR1 inhibitor SR48692 significantly nullified ASD's anti-NETs effects and dampened cAMP pathway activation. Mechanistically, suppression of PKAc via H89 negated ASD's anti-NETs effects but did not affect NTSR1. Our study suggests that ASD may reduce NETs formation and neuroinflammation, potentially involving the NTSR1/PKAc/PAD4 pathway post-ICH, underlining the potential of ASD in mitigating neuroinflammation through its anti-NETs properties.

Endothelial pyroptosis-driven microglial activation in choroid plexus mediates neuronal apoptosis in hemorrhagic stroke rats.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with alarmingly high rates of disability and mortality, and current therapeutic options are suboptimal. A critical component of ICH pathology is the initiation of a robust inflammatory response, often termed "cytokine storm," which amplifies the secondary brain injury following the initial hemorrhagic insult. The precise sources and consequences of this cytokine-driven inflammation are not fully elucidated, necessitating further investigation. METHODS: To address this knowledge gap, our study conducted a comprehensive cytokine profiling using Luminex® assays, assessing 23 key cytokines. We then employed single-cell RNA sequencing and spatial transcriptomics at three critical time points post-ICH: the hyperacute, acute, and subacute phases. Integrating these multimodal analyses allowed us to identify the cellular origins of cytokines and elucidate their mechanisms of action. RESULTS: Luminex® cytokine assays revealed a significant upregulation of IL-6 and IL-1ß levels at the 24-h post-ICH time point. Through the integration of scRNA-seq and spatial transcriptomics in the hemorrhagic hemisphere of rats, we observed a pronounced activation of cytokine-related signaling pathways within the choroid plexus. Initially, immune cell presence was sparse, but it surged 24 h post-ICH, particularly in the choroid plexus, indicating a substantial shift in the immune microenvironment. We traced the source of IL-1ß and IL-6 to endothelial cells, establishing a link to pyroptosis. Endothelial pyroptosis post-ICH induced the production of IL-1ß and IL-6, which activated microglial polarization characterized by elevated expression of Msr1, Lcn2, and Spp1 via the NF-κB pathway in the choroid plexus. Furthermore, we identified neuronal populations undergoing apoptosis, mediated by the Lcn2-SLC22A17 pathway in response to IL-1ß and IL-6 signaling. Notably, the inhibition of pyroptosis using VX-765 significantly mitigated neurological impairments. CONCLUSIONS: Our study provides evidence that endothelial pyroptosis, characterized by the release of IL-1ß and IL-6, triggers microglial polarization through NF-κB pathway activation, ultimately leading to microglia-mediated neuronal apoptosis in the choroid plexus post-ICH. These findings suggest that targeted therapeutic strategies aimed at mitigating endothelial cell pyroptosis and neutralizing inflammatory cytokines may offer neuroprotection for both microglia and neurons, presenting a promising avenue for ICH treatment.

A machine learning approach for predicting perihematomal edema expansion in patients with intracerebral hemorrhage.

OBJECTIVES: Preventing the expansion of perihematomal edema (PHE) represents a novel strategy for the improvement of neurological outcomes in intracerebral hemorrhage (ICH) patients. Our goal was to predict early and delayed PHE expansion using a machine learning approach. METHODS: We enrolled 550 patients with spontaneous ICH to study early PHE expansion, and 389 patients to study delayed expansion. Two imaging researchers rated the shape and density of hematoma in non-contrast computed tomography (NCCT). We trained a radiological machine learning (ML) model, a radiomics ML model, and a combined ML model, using data from radiomics, traditional imaging, and clinical indicators. We then validated these models on an independent dataset by using a nested 4-fold cross-validation approach. We compared models with respect to their predictive performance, which was assessed using the receiver operating characteristic curve. RESULTS: For both early and delayed PHE expansion, the combined ML model was most predictive (early/delayed AUC values were 0.840/0.705), followed by the radiomics ML model (0.799/0.663), the radiological ML model (0.779/0.631), and the imaging readers (reader 1: 0.668/0.565, reader 2: 0.700/0.617). CONCLUSION: We validated a machine learning approach with high interpretability for the prediction of early and delayed PHE expansion. This new technique may assist clinical practice for the management of neurocritical patients with ICH. KEY POINTS: • This is the first study to use artificial intelligence technology for the prediction of perihematomal edema expansion. • A combined machine learning model, trained on data from radiomics, clinical indicators, and imaging features associated with hematoma expansion, outperformed all other methods.

Ventriculoperitoneal shunt for tuberculous meningitis-associated hydrocephalus: long-term outcomes and complications.

BACKGROUND: Hydrocephalus is a frequent complication of tuberculous meningitis (TBM), and ventriculoperitoneal shunt (VPS) has been shown to improve short-term prognosis for patients with TBM-associated hydrocephalus. However, questions remain about long-term prognosis and shunt-related complications. This study aims to provide a comprehensive assessment of both long-term prognosis and shunt-related complications in patients with TBM-induced hydrocephalus who have undergone VPS treatment. METHODS: This retrospective study analyzed the clinical data of TBM patients with hydrocephalus treated with VPS at Peking Union Medical College Hospital between December 1999 and February 2023. Both short-term outcomes at discharge and long-term outcomes during follow-up were examined. Prognosis and shunt-related complications were assessed using the modified Rankin Scale (mRS) and the Activity of Daily Living (ADL) score to evaluate neurological function and autonomic living ability, respectively. RESULTS: A total of 14 patients with TBM-associated hydrocephalus were included in this study. Of these, 92.9% (13/14) exhibited favorable short-term outcomes, while 57.1% (8/14) showed positive long-term outcomes. Initial results indicated 6 complete recoveries (CR), 7 partial recoveries (PR), and 1 treatment failure. No catheter-related complications were observed initially. Long-term results included 4 CRs, 4 PRs, and 6 treatment failures. A variety of shunt surgery-related complications were noted, including three instances of catheter obstruction, one of incision infection, one of catheter-related infection, one of acute cerebral infarction, and one of transient peritoneal irritation accompanied by diarrhea. CONCLUSIONS: VPS appears to be an effective and well-tolerated treatment for TBM-associated hydrocephalus, efficiently alleviating acute intracranial hypertension. Nonetheless, continuous long-term monitoring and proactive management are essential to mitigate the risk of catheter-related complications.

Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1ß, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software. RESULTS: A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1ß: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6-9). CONCLUSIONS: This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS. PROSPERO REGISTRATION NUMBER: CRD42022368744.

Validation of perihematomal edema expansion as a new imaging biomarker to predict clinical outcome in patients with intracerebral hemorrhage.

OBJECTIVES: The use of hematoma expansion (HE) in intracerebral hemorrhage (ICH) patients is limited due to its low sensitivity. Perihematomal edema (PHE) has been considered an important marker of secondary brain injury after ICH. Enrolling PHE expansion to redefine traditional ICH expansion merits exploration. MATERIALS AND METHODS: This study analyzed a cohort of patients with spontaneous ICH. The hematoma and PHE were manually segmented. Logistic regression analysis was utilized to identify risk factors for poor outcomes. Receiver operating characteristic curve analysis was performed to calculate the predictive values of PHE expansion and HE. Poor neurological outcome was defined as a modified Rankin Scale score of 4-6 at 90 days. RESULTS: Overall, 223 target patients were enrolled in the study. Multivariable analysis showed the larger PHE expansion is the independent risk factors for poor prognosis. The predictive value of absolute PHE expansion (AUC=0.776, sensitivity=67.9%, specificity=77.0%) was higher than that of absolute HE (AUC=0.573, sensitivity=41.7%, specificity=87.1%) and HE (>6 ml) (AUC=0.594, sensitivity=23.8%, specificity=95.0%). The best cutoff for early absolute/relative PHE expansion resulting in a poor outcome was 5.96 ml and 31%. CONCLUSIONS: Early PHE expansion was associated with a poor outcome, characterized by a better predictive value than HE.

Assessing the Evolution of Intracranial Hematomas by using Animal Models: A Review of the Progress and the Challenges.

Stroke has become the second leading cause of death in people aged higher than 60 years, with cancer being the first. Intracerebral hemorrhage (ICH) is the most lethal type of stroke. Using imaging techniques to evaluate the evolution of intracranial hematomas in patients with hemorrhagic stroke is worthy of ongoing research. The difficulty in obtaining ultra-early imaging data and conducting intensive dynamic radiographic imaging in actual clinical settings has led to the application of experimental animal models to assess the evolution of intracranial hematomas. Herein, we review the current knowledge on primary intracerebral hemorrhage mechanisms, focus on the progress of animal studies related to hematoma development and secondary brain injury, introduce preclinical therapies, and summarize related challenges and future directions.

Diagnosis and treatment of low T3 syndrome in neurocritical patients.

WHAT IS KNOWN AND OBJECTIVE: Low levels of serum triiodothyronine (T3) are a strong predictor of mortality and poor prognosis in critical care patients. Few reports, however, have focused on neurocritical patients. The application of hormone replacement therapy (HRT) in the treatment of neurocritical patients with low T3 syndrome remains controversial. We studied the role of low T3 state as a predictor of outcomes in neurocritical patients and examined the effect of HRT on prognosis. METHODS: A retrospective analysis was performed on the data of 32 neurocritical patients with low T3 syndrome who were admitted to the neuro-intensive care unit of Peking Union Medical College Hospital between January 2012 and October 2018. While 18/32 (56.25%) patients received HRT (HRT group; n = 18), 14/32 (43.75%) patients did not receive HRT (non-HRT group; n = 14). Patients were followed up for periods ranging from 3 months to 72 months. Baseline clinical and laboratory data were compared between the two groups using Mann-Whitney U tests or the t tests. Overall survival was assessed by Kaplan-Meier curve and compared by log-rank tests. Univariate and multivariate regression analyses were performed to identify the factors associated with prognosis and estimate the effect of HRT. We also assessed the influence of HRT on final neurological function, using the Glasgow Coma Scale (GCS) and the Glasgow Outcome Scale (GOS) scores. RESULTS AND DISCUSSION: The neurocritical events in our cohort included post-operative complications (n = 18), traumatic brain injury (n = 8) and spontaneous intracerebral haemorrhage (n = 6). Mean GCS score in the cohort was 6.41 (6.44 ± 3.14 in HRT group vs 6.36 ± 2.06 in non-HRT group). A total of 15/32 (46.87%) deaths were recorded (7 in the HRT group, 8 in the non-HRT group). In the HRT group, 15 patients underwent repeat thyroid function tests after completion of HRT; the low T3 situation was corrected in only 5/15 (33.3%) patients. Overall survival was significantly shorter in the non-HRT group than in the HRT group (16.45 months vs 47.47 months; P = .034). In univariate regression analysis, the HRT group has the lower mortality risk than the non-HRT group (HR = 0.301, 95% Cl: 0.094-0.964; P = .043). However, multivariate regression analysis showed no significant difference in mortality risk between the two groups (HR = 0.340 95% CI: 0.099-1.172; P = .087). There was no significant difference in effects of HRT on the short- and long-term neurological function between the groups. WHAT IS NEW AND CONCLUSION: Low T3 syndrome may influence the prognosis of neurocritical patients, attention should be paid to the changes in serum T3 levels during treatment. Although it is unclear to what extent HRT can improve the short or long-term outcomes of neurological function, it can significantly improve the survival rates of neurocritical patients.

Systemic autoimmune diseases complicated with hydrocephalus: pathogenesis and management.

Systemic autoimmune diseases (SAIDs) represent a group of syndromes involving at least two organ systems. Classical SAIDs include connective tissue diseases, vasculitis, and granulomatous diseases, many of which involve the nervous system and result in different neurological manifestations. Hydrocephalus can be a rare but lethal complication of various SAIDs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), sarcoidosis, and primary vasculitis. However, the pathogenesis of SAIDs complicated with different types of hydrocephalus is varied and difficult to determine using the existing published data, and various manifestations and expressive forms of the conditions bring a substantial challenge to a timely clinical diagnosis and treatment. The commonly used medical management programs based on the etiology of hydrocephalus are anti-inflammatory or anti-infectious therapies, while surgical management such as ventriculoperitoneal shunts is effective most of the time. Further research should be directed toward improving our understanding of the pathogenesis of these conditions and determining the most effective method for treating this life-threatening condition.

Bromadiolone poisoning leading to subarachnoid haemorrhage: A case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Many cases of rodenticide poisoning have been reported. Bromadiolone, often called a super-warfarin, is a second-generation dicoumarin rodenticide with long half-life. The main clinical manifestations of bromadiolone poisoning are excessive or inappropriate bleeding of skin mucosa, digestive tract and urinary tract. However, the phenomenon of central nervous system (CNS) toxicity is an uncommon medical emergency. We present a case of SAH and intracerebral haematoma mediated by bromadiolone intoxication, revealing that bromadiolone poisoning might cause intracerebral haematoma. CASE DESCRIPTION: A 44-year-old woman presented with skin mucosa haemorrhage and haematuresis initially. The patient developed lethargy, headache, nausea and vomiting. The toxicology test result revealed that the presence of bromadiolone in her blood. Coagulation test results showed a longer prothrombin time (PT), activated partial thromboplastin time (APTT) and a high international normalized ratio (INR). SAH, frontal lobe haematoma, midline shift and brain oedema were discovered by skull CT examination. The coagulation disorders were addressed after the treatment of vitamin K and fresh frozen plasma. The intracranial symptoms were relieved after surgery and the treatment with mannitol. WHAT IS NEW AND CONCLUSION: This case suggests that bromadiolone poisoning should be diagnosed and treated as early as possible. Bromadiolone poisoning might cause SAH and intracerebral haematoma, which is rare but potentially lethal. It is important to strengthen the diagnosis and post-treatment monitoring.

Protection of Nerve Injury with Exosome Extracted from Mesenchymal Stem Cell.

OBJECTIVE: To investigate the protective effect of Exosomes from human adipose-derived mesenchymal stem cells (hAMSCs) in neural injury induced by glutamate and its possible mechanism. METHODS: Characteristics of Exosomes from hAMSCs were identified by electron microscopy and Western blot analysis. Cytokines that might play a major role in the protective effect were tested by enzyme-linked immunosorbent assay (ELISA). The protective action of Exosome and its possible signaling pathway were researched by the in vitro neural injury induced by glutamate, including control group (without Glu), Glu group (dealing with Glu), Glu+Exo group (dealing with Glu +100 ng/ml Exo), Glu+Exo+Akt group (dealing with Glu+100 ng/ml Exo+10 µmol/L Akt), Glu+Exo+Erk group (dealing with 100 ng/ml Glu+100 ng/ml Exo+10 µmol/L Erk), and Glu+Exo+TrkB group (dealing with Glu+100 ng/ml Exo +10 µmol/L TrkB). RESULTS: Exosomes from hAMSCs had similar sizes to those isolated from other kinds of cells, and expressed the characteristic proteins such as CD63, CD81, HSP70, and HSP90. Cytokines that had neurotrophic effects on Exosomes were mainly insulin-like growth factor and hepatocyte growth factor, with the concentration being 9336.49±258.63 and 58,645.50±16,014.62, respectively; brain derived neurotrophic factor, nerve growth factor,and vascular endothelial growth factor had lower levels, with the concentration being 1928.25±385.47, 1136.94±5.99, and 33.34±9.43, respectively. MTS assay showed that the PC12 cell survival rates were 0.842±0.047, 0.306±0.024, 0.566±0.026, 0.461±0.016, 0.497±0.003, and 0.515±0.034 in the control group, Glu group, Glu+Exo group, Glu+Exo+Akt group, Glu+Exo+Erk group, and Glu+Exo+TrkB group; obviously, it was significantly lower in Glu group than in control group (P=0.02), significantly higher in Glu+Exo group than in Glu group (P=0.01), and significantly lower in Glu+Exo+Akt group than in Glu+Exo group (P=0.01). CONCLUSION: Exosomes secreted from hAMSCs have protective effect against neuron damage induced by glutamate, which may be mediated through activating the PI3/K-Akt signalling pathway.

[Diagnosis and Treatment of Pituitary Carcinoma].

The early diagnosis and treatment of pituitary carcinoma is difficult. The diagnosis is often delayed, and the confirmation of a diagnosis requires the presence of distant subarachnoid,brain or systemic metastasis from the primary pituitary tumor in the sella and also needs the evidences of pathology and imaging of the primary pituitary carcinoma and metastases. Treatment of pituitary carcinoma includes surgery, radiation therapy ,hormone therapy, chemotherapy, and molecularly targeted therapy; however, these methods are mainly palliative and can not prolong the survival. The prognosis remains poor. Efforts should be made to develop more effective diagnosis and treatment options.

Preclinical safety evaluation of human mesenchymal stem cell transplantation in cerebrum of nonhuman primates.

The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 × 10(5) cells/kg), high dose (2.5 × 10(6) cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS were injected into each monkey for 2 times, with an interval of 3 weeks. The injection point was located outside of the right putamen, according to a stereotactic map and preoperative magnetic resonance imaging of the monkeys. Animal health, behavior, biophysical and biochemical parameters, and brain neurological function were routinely monitored over a 6-month period posttransplantation, and the histopathologic examinations were also performed. The results showed that local pathologic damage including local tissue necrosis and inflammation was induced after the injection. The damage of low-dose and high-dose groups was greater than that of the control group, yet over time, the damage could be repaired gradually. No major hMSCs-associated changes were induced from other indicators, and the transplantation of hMSCs in monkeys did not affect total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore conclude that transplantation of hMSCs to the cerebrum represents a safe alternative for clinical application of neurological disorders.

Single-cell RNA sequencing identifies a subtype of FN1 + tumor-associated macrophages associated with glioma recurrence and as a biomarker for immunotherapy.

BACKGROUND: Glioma is the most common primary malignant tumor in the brain, and even with standard treatments including surgical resection, radiotherapy, and chemotherapy, the long-term survival rate of patients remains unsatisfactory. Recurrence is one of the leading causes of death in glioma patients. The molecular mechanisms underlying glioma recurrence remain unclear. METHODS: Our study utilized single-cell sequencing, spatial transcriptomics, and RNA-seq data to identify a subtype of FN1 + tumor-associated macrophages (FN1 + TAMs) associated with glioma recurrence. RESULTS: This study revealed an increased abundance of FN1 + TAMs in recurrent gliomas, indicating their potential involvement as a critical factor in glioma recurrence. A negative correlation was observed between the abundance of FN1 + TAMs in primary gliomas and the interval time to recurrence, suggesting poor prognosis for glioma patients with high levels of FN1 + TAMs. Further investigation showed that FN1 + TAMs were enriched in hypoxic tumor regions, implying that metabolic changes in tumors drive the production and recruitment of FN1 + TAMs. Additionally, FN1 + TAMs were found to contribute to the regulation of an immunosuppressive microenvironment in gliomas, and their abundance might serve as an indicator of patients' sensitivity to immunotherapy. Finally, we developed a user-friendly website, PRIMEG ( http://www.szflab.site/PRIMEG/ ), for exploring the immune microenvironment of primary and recurrent gliomas. CONCLUSION: Our findings highlight a subtype of FN1 + TAMs associated with glioma recurrence, providing new insights into potential therapeutic targets. Moreover, the abundance of FN1 + TAMs hold promise for predicting immune therapy response and aiding in more precise risk stratification of recurrent glioma patients.

Single-cell and Spatial Transcriptomics Reveals Ferroptosis as The Most Enriched Programmed Cell Death Process in Hemorrhage Stroke-induced Oligodendrocyte-mediated White Matter Injury.

Intracerebral hemorrhage (ICH) is a severe stroke subtype with limited therapeutic options. Programmed cell death (PCD) is crucial for immunological balance, and includes necroptosis, pyroptosis, apoptosis, ferroptosis, and necrosis. However, the distinctions between these programmed cell death modalities after ICH remain to be further investigated. We used single-cell transcriptome (single-cell RNA sequencing) and spatial transcriptome (spatial RNA sequencing) techniques to investigate PCD-related gene expression trends in the rat brain following hemorrhagic stroke. Ferroptosis was the main PCD process after ICH, and primarily affected mature oligodendrocytes. Its onset occurred as early as 1 hour post-ICH, peaking at 24 hours post-ICH. Additionally, ferroptosis-related genes were distributed in the hippocampus and choroid plexus. We also elucidated a specific interaction between lipocalin-2 (LCN2)-positive microglia and oligodendrocytes that was mediated by the colony stimulating factor 1 (CSF1)/CSF1 receptor pathway, leading to ferroptosis induction in oligodendrocytes and subsequent neurological deficits. In conclusion, our study highlights ferroptosis as the primary PCD mechanism, emerging as early as 1 hour post-ICH. Early therapeutic intervention via the suppression of microglial LCN2 expression may alleviate ferroptosis-induced damage in oligodendrocytes and associated neurological deficits, thus offering a promising neuroprotective strategy following ICH.

Unraveling dynamic immunological landscapes in intracerebral hemorrhage: insights from single-cell and spatial transcriptomic profiling.

Intracerebral hemorrhage (ICH) poses a formidable challenge in stroke management, with limited therapeutic options, particularly in the realm of immune-targeted interventions. Clinical trials targeting immune responses post-ICH have encountered setbacks, potentially attributable to the substantial cellular heterogeneity and intricate intercellular networks within the brain. Here, we present a pioneering investigation utilizing single-cell RNA sequencing and spatial transcriptome profiling at hyperacute (1 h), acute (24 h), and subacute (7 days) intervals post-ICH, aimed at unraveling the dynamic immunological landscape and spatial distributions within the cerebral tissue. Our comprehensive analysis revealed distinct cell differentiation patterns among myeloid and lymphocyte populations, along with delineated spatial distributions across various brain regions. Notably, we identified a subset of lymphocytes characterized by the expression of Spp1 and Lyz2, termed macrophage-associated lymphocytes, which exhibited close interactions with myeloid cells. Specifically, we observed prominent interactions between Lgmn+Macro-T cells and microglia through the spp1-cd44 pathway during the acute phase post-ICH in the choroid plexus. These findings represent a significant advancement in our understanding of immune cell dynamics at single-cell resolution across distinct post-ICH time points, thereby laying the groundwork for exploring critical temporal windows and informing the development of targeted therapeutic strategies.

siRNA-mediated knockdown of SMC1A expression suppresses the proliferation of glioblastoma cells.

SMC1A is a member of cohesin complex which has essential functions in cell cycle progression and DNA repair. Therefore, we choose SMC1A as a target gene therapy of glioblastoma. It is well known that glioblastoma has very low survival rate because of ineffectiveness of conventional treatments. This study was designed to explore the possibilities of small interfering RNA (siRNA)-mediated SMC1A silencing as alternative method of treatment. We found that the lentivirus-mediated RNAi system efficiently decreased the expression level of SMC1A. Inhibiting SMC1A expression efficiently (P < 0.001) resulted in inhibiting the proliferation and colony formation of U251 and U87MG cells. Moreover, we found that SMC1A silencing led to S cell-cycle arresting. Collectively, these results demonstrated the possibility of siRNA-mediated silencing of SMC1A as a therapeutic tool for the treatment of glioblastoma.

Transsphenoidal approach for pituitary adenomas in patients with McCune-Albright syndrome.

The feasibility of transsphenoidal approach under a guidance of neuronavigation was explored to remove pituitary adenomas for patients with McCune-Albright syndrome (MAS). From August, 2008 to July, 2010, there were 5 patients diagnosed with MAS associated with a pituitary adenoma in our department of Peking Union Medical College Hospital. All the patients underwent transsphenoidal surgery for the removal of pituitary adenomas with the assistant of neuronavigation and all the procedures went uneventfully. Four of the five patients have got cured radiologically by imaging and 3 of them have got cured based on endocrinological criteria. Transsphenoidal approach under the neuronavigational guidance is a safe and effective management for the MAS patients with pituitary adenomas.

[Significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery].

OBJECTIVE: To explore the significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery. METHODS: For 22 patients with pituitary adenomas over a period of 2 years at Peking Union Medical College Hospital, resection of pseudocapsule was applied for complete tumor removal. Pituitary function test and radiological imaging were performed at pre-operation, 3 months post-operation and at subsequent 6-12 months intervals postoperatively. RESULTS: All pituitary adenomas were totally removed under microscope. The symptoms of headache, disorder of sight and visual field disappeared postoperatively in nonfunctional pituitary adenomas. The GH levels of 2/5 growth hormone secreting adenoma patients were 4.2 and 7.7 µg/L while it was under 1 µg/L for another 3. The postoperative level of prolactin was 4.3 µg/L in prolactin secreting adenoma. The level of adrenocorticotropic hormone decreased under 5 ng/L except one was 15.7 ng/L. Leakage of cerebrospinal fluid occurred intraoperatively in 3 patients and postoperatively in 1. No leakage was found after repair. Diabetes insipidus occurred in one patient and was controlled with Minirin. Pseudocapsule was confirmed by pathological examination. Special staining revealed reticulum fibers in pseudocapsule. CONCLUSION: Resection of pseudocapsule may achieve a higher remission rate without deteriorating pituitary function.

[Advances in the pathogenesis and treatment of neurosurgical emergency with coagulation disorders].

Neurosurgical emergencies including intracranial hemorrhage and head trauma have high mortality and morbidity rates and meanwhile are often accompanied with coagulation disorders. On one hand, coagulation disorder follows traumatic brain injury;on the other hand, the increasing use of anticoagulant and antiplatelet treatment for cardiovascular diseases increases the risk of death among patients with brain trauma or bleeding. Once the intracranial pressure increases, such patients need emergency surgical intervention, but coagulation disorder is a relative contraindication. This article reviews the pathogenesis and treatment of coagulation disorders in patients with neurosurgical emergency. It also analyzes clinical monitoring indices for such patients and their variations and summarizes the strategies and measures of perioperative management.