Ischemic stroke, a critical neurological disorder resulting from abrupt cerebral blood flow interruption, remains a leading cause of global mortality and chronic disability. Despite advancements in reperfusion therapies, many survivors still suffer significant neurological deficits, primarily attributed to ischemia-reperfusion injury-induced oxidative stress and neuroinflammation. To address these challenges, we designed cerium-curcumin hybrid nanoparticles (Ce-Cur NPs) by leveraging the coordination interaction between redox-active cerium ions and curcumin's beta-diketone moiety. These Ce-Cur NPs were engineered to alleviate ROS-mediated secondary injuries and promote neural repair by leveraging their remarkable ROS scavenging capabilities, which mimic enzymatic activities to effectively neutralize superoxide and hydroxyl radicals. Furthermore, M1 polarized macrophage-derived membranes were employed to enhance the targeted delivery of Ce-Cur NPs to ischemic regions, while transferrin receptor (TfR)-activated peptides enabled efficient receptor-mediated transcytosis across the blood-brain barrier. In vivo studies using a middle cerebral artery occlusion (MCAO) model demonstrated that TfR-M1-Ce-Cur NPs successfully localized to the ischemic brain, significantly reduced infarct volume, and preserved neuronal integrity. Enhanced neurogenesis and improved functional recovery were observed, underscoring the therapeutic potential of Ce-Cur NPs as a versatile platform for ischemic stroke treatment. This approach provides a robust and evidence-based solution to enhance clinical outcomes for patients with ischemic stroke.

Central nervous system (CNS) injury is a leading cause of death and long-term disability worldwide. Neurological deficits reflect disruption of central neural circuits. A major barrier to circuit repair is the intrinsically low regenerative potential of adult CNS neurons-linked in part to failure of injury-induced nuclear export of class IIa histone deacetylases (notably HDAC5)-together with a hostile post-injury microenvironment. Here we present a multifunctional nanosystem, encapsulating the class IIa HDAC4/5-selective inhibitor LMK-235 and featuring an electroactive polyaniline coating with asymmetrically distributed 5-hydroxytryptamine moieties. Upon reaching the lesion, our nanosystem assembles into large-pore scaffolds that (i) inhibit the activity of nuclear-retained class IIa HDACs in neurons and thereby reactivate intrinsic regenerative programs, (ii) regulate microglial activation to mitigate neuroinflammation, and (iii) provide an electroactive interface promoting activity-dependent synaptic reconnection. This multi-pronged approach illustrates an integrated platform with translational potential for CNS disorders in which circuit disconnection constrains recovery.

Intracranial aneurysm, an abnormal bulging or outpouching of the arterial wall, is a prevalent condition among the global adult population.1-3 With the advancement of techniques and materials, endovascular intervention has become the first-line treatment for intracranial aneurysms in routine cases. However, microsurgical clipping remains irreplaceable because of its advantages, including lower recurrence rates, cost-effectiveness, and a well-established approach to direct vascular reconstruction.4-7 We present the case of a 63-year-old woman with a trilobed aneurysm located on the anterior communicating artery (Video 1). Diagnostic imaging demonstrated a trilobed aneurysm of the anterior communicating artery, posing a significant risk of rupture. We used a conventional pterional approach. Although one daughter sac was managed quickly, the other 2 presented a significant challenge. Despite repeated attempts with various standard and fenestrated clips, we could not fully occlude the aneurysm without compromising vital branches. Therefore, we intraoperatively modified the clip configuration for the first time. Through meticulous adjustment, we achieved a precise fit that completely secured the aneurysm and successfully reconstructed the anterior communicating artery. For special aneurysms, bipolar electrocoagulation shaping may also be an option, as reported by some neurosurgeons for complex anterior communicating artery aneurysms.8,9 However, we have introduced an additional technique-aneurysm clip shaping-to provide another option for surgery. In conclusion, this case demonstrates the successful microsurgical obliteration of a complex anterior communicating artery aneurysm. Surgical clipping remains a definitive and durable curative treatment for complex aneurysms. Informed consent was obtained from the patient for the procedure and publication of this operative video.

BACKGROUND Hemodynamic alterations caused by internal carotid artery (ICA) dissection (ICAD) may obscure the identification of intracranial aneurysms. These flow disturbances can compromise angiographic assessment and influence therapeutic decision-making. OBSERVATIONS A 51-year-old female patient underwent digital subtraction angiography (DSA), which initially suggested the presence of a supraclinoid ICA aneurysm, prompting a referral for surgical intervention. However, anomalous collateral circulation patterns raised suspicion of proximal ICA pathology. Subsequent focused angiography identified a cervical ICA origin dissection. After endovascular stent placement, repeat imaging demonstrated that the previously observed “aneurysm” was in fact a hemodynamically distorted posterior communicating artery infundibulum. Thus, the scheduled craniotomy was deemed unnecessary and canceled. LESSONS This report represents the first documented instance of a flow-mediated pseudolesion mimicking an intracranial aneurysm secondary to proximal ICAD. Although DSA remains the diagnostic criterion standard, this case underscores the potential for hemodynamic artifacts to yield misinterpretations. Comprehensive evaluation of cerebrovascular flow dynamics is essential to mitigate diagnostic errors and prevent unwarranted invasive procedures. https://thejns.org/doi/10.3171/CASE25652

Rheumatoid arthritis (RA) is associated with an increased risk of brain diseases, yet the underlying biological mechanisms remain poorly understood. Using data from the UK Biobank, including blood-based biomarkers, brain imaging, and diagnostic records, we investigated the roles of immunometabolic and brain structure alterations in the link between RA and brain diseases. The effects of antirheumatic treatments were evaluated using Cox proportional hazards models. To ensure a clear temporal sequence, only individuals with RA diagnosed before baseline were included. The cohort comprised 2534 prevalent RA cases (mean age: 59.80 ± 6.99 years; 70.84

Background: Ischemic stroke is considered a fatal ischemic disease with high mortality and morbidity. Acute ischemic stroke is a cascade of inflammatory reactions, which not only causes vascular degeneration but also leads to neurological disorders. During this period, the rapid response of neutrophil-dominated granulocytes releases cytokines and chemokines to affect tissue repair. Thus, effective regulation of neutrophils appears to be the key in treating major organ injuries associated with inflammation. Methods: This study developed a semisynthetic sulfated chitosan (SCS) associated with the functional sulfated groups. The immunoregulatory effects of SCS on neutrophils were tested by Real-Time Quantitative Reverse Transcription (RT-PCR), ELISA and immunofluorescence staining at gene and protein levels in vitro. Flow cytometry, WB and PCR were used to study the effect of neutrophils on macrophages, indicating the regulation of the inflammatory cascade by SCS. Acute ischemic stroke model was established to verify the effectiveness and the regulation of inflammatory cascade of SCS. Finally, the lower limb ischemia model was used to verify the universality of SCS in the treatment of ischemic diseases, especially with regard to acute inflammatory-related major organ damage. Results: SCS can not only promote neutrophil apoptosis, but also enable neutrophils to produce vascular-related subsets to regulate immunity and promote angiogenesis. Neutrophil stimulated by SCS mediated macrophage polarization via IL-10-induced Stat3 signaling pathway to weaken the inflammatory cascade. In animal models of ischemic hind limb and ischemic stroke, SCS had demonstrated its ability to shorten the acute inflammatory period, as indicated by neutrophil, and accelerate the subsequent repair period characterized by the presence of M2 macrophages. Additionally, SCS effectively inhibits the expression of MMP-9 to provide a favorable environment for rapid extracellular matrix reconstruction. Encouragingly, treatment with SCS had been shown to reduce the expansion of the infarct volume by approximately 20% in our experiments. Conclusion: This study underscores the effect of SCS in regulating the heterogeneity of neutrophils in order to suppress the initiation of inflammation to treat ischemic stroke. Crucially, our approach relies on non-exogenous growth factors and cells, highlighting its remarkable potential for clinical translatability in the treatment of major organ injuries.

Abstract Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.

The Kawase approach is one of the most used trajectories in skull base surgery. The exposure range of the approach and its correlation with skull base anatomy still demand more exploration. With the help of digital rebuilding, analysis, and measurement, we evaluated the exposure range of the Kawase and extended Kawase approaches and analyzed the correlation between the exposure range and the variants of the petrosal and clival anatomy. The finding of the study demonstrated that compared to the sub-temporal approach, the Kawase approach and the extended Kawase approach significantly added the exposure range in the upper, middle, and partial inferior regions of the clivus. The gains in the exposure volume and area are more when the manipulation angle is less than 135°.

Since 2019,in order to rapidly improve the clinical capabilities of primary-level physicians,the Navy has comprehensively carried out standardized training for residents.The author made some thoughts on how neurosurgery can better complete the teaching work of naval residents,and better improve the clinical knowledge and ability of naval training physicians,so as to better serve the army and improve the combat support capabilities of the army.He also communicated and discussed with the rotating naval training physicians in neurosurgery many times,and proposed a comprehensive and comprehensive teaching model and method.For example,the tutor-led teaching system,case-based learning（CBL） combined with problem-based learning（PBL） teaching model,the skill simulation training system,and the learning and reference of new teaching methods in recent years,such as Virtual Reality（VR）.New technologies such as mixed reality technology and 3D printing interaction,etc.The application of these new methods has been proved to fully mobilize the autonomy and enthusiasm of residents.Meanwhile,it promotes the understanding and mastery of basic theoretical knowledge,and facilitate the level of clinical technology.and overall quality improvement.

Apoptotic vesicles (ApoVs) hold great promise for inflammatory regulation and tissue repair. However, little effort has been dedicated to developing ApoV-based drug delivery platforms, while the insufficient targeting capability of ApoVs also limits their clinical applications. This work presents a platform architecture that integrates apoptosis induction, drug loading, and functionalized proteome regulation, followed by targeting modification, enabling the creation of an apoptotic vesicle delivery system to treat ischemic stroke. Briefly, α-mangostin (α-M) was utilized to induce mesenchymal stem cell (MSC) apoptosis while being loaded onto MSC-derived ApoVs as an anti-oxidant and anti-inflammatory agent for cerebral ischemia/reperfusion injury. Matrix metalloproteinase activatable cell-penetrating peptide (MAP), a microenvironment-responsive targeting peptide, was modified on the surface of ApoVs to obtain the MAP-functionalized α-M-loaded ApoVs. Such engineered ApoVs targeted the injured ischemic brain after systemic injection and achieved an enhanced neuroprotective activity due to the synergistic effect of ApoVs and α-M. The internal protein payloads of ApoVs, upon α-M activation, were found engaged in regulating immunological response, angiogenesis, and cell proliferation, all of which contributed to the therapeutic effects of ApoVs. The findings provide a universal framework for creating ApoV-based therapeutic drug delivery systems for the amelioration of inflammatory diseases and demonstrate the potential of MSC-derived ApoVs to treat neural injury.

Mesenchymal stem cells (MSCs) exhibited remarkable therapeutic potential in ischemic stroke due to their exceptional immunomodulatory ability and paracrine effect; they have also been regarded as excellent neuroprotectant delivery vehicles with inflammatory tropism. However, the presence of high levels of reactive oxygen species (ROS) and an oxidative stress environment at the lesion site inhibits cell survival and further therapeutic effects. Using bioorthogonal click chemistry, ROS-responsive luteolin-loaded micelles were tethered to the surface of MSCs. As MSCs migrated to the ischemic brain, the micelles would achieve ROS-responsive release of luteolin to protect MSCs from excessive oxidative damage while inhibiting neuroinflammation and scavenging ROS to ameliorate ischemic stroke. This study provided an effective and prospective therapeutic strategy for ischemic stroke and a framework for a stem cell-based therapeutic system to treat inflammatory cerebral diseases.

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion. Downregulation of microRNA (miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia. However, the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated. In this study, mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion. Agomir-455-5p, antagomir-455-5p, and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion (MCAO). The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood. Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue, reduced the cerebral infarct volume, and improved neurological function. Furthermore, primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion. miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels, inhibited microglia activation, and reduced the production of the inflammatory factors tumor necrosis factor-α and interleukin-1β. These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.

Background: Activation of NLRP3 inflammasome accelerates the formation of atherosclerotic plaques. Here, we evaluated the effects of inflammation on the expression of the NLRP3 inflammasome in endothelial cells (ECs). Methods: The effect of TNF-alpha on transcytosis of LDL was measured. VCAM-1 binding peptide targeting cationic liposomes (PCLs) were prepared as siRNA vectors. Methylated NLRP3 siRNA was encapsulated into the PCLs to knock down NLRP3 in vitro and in vivo. In rats with partial carotid ligation, TNF-alpha-induced LDL retention in the carotid artery endothelium was observed. In ApoE(-/-) mice, NLRP3 siRNA-PCLs were injected intravenously to observe their effect on the formation of atherosclerosis. Results: Our results showed that TNF-alpha upregulated NLRP3 in ECs, promoting the assembly of the NLRP3 inflammasome and processing of pro-IL-1 beta into IL-1 beta. Moreover, TNF-alpha accelerated LDL transcytosis in ECs. Knockdown of NLRP3 prevented TNF-alpha-induced NLPR3 inflammasome/IL-1 beta signaling and LDL transcytosis. Using optimized cationic liposomes to encapsulate methylated NLRP3 siRNA, resulting in targeting of VCAM-1-expressing ECs, to knockdown NLRP3, TNF-alpha-induced NLRP3 inflammasome activation and LDL transcytosis were prevented. Using the partial carotid ligation as an atherosclerosis rat model, we found that local administration of NLRP3 siRNA-PCLs efficiently knocked down NLPR3 expression in the carotid endothelium and dramatically attenuated the deposition of atherogenic LDL in carotid ECs in TNF-alpha-challenged rats. Furthermore, NLRP3 siRNA-PCLs were injected intravenously in ApoE(-/-) mice, resulting in reduced plaque formation. Conclusion: These findings established a novel strategy for targeting the NLRP3 inflammasome using NLRP3 siRNA-PCLs to interrupt LDL transcytosis, representing a potential novel therapy for atherosclerosis.

A series of non-isocyanate poly(ether urethane) (PEU) were prepared by an environmentally friendly route based on dimethyl carbonate, diols and a polyether. The effect of the chemical structure of polyurethane hard segments on the properties of this kind of PEU was systematically investigated in this work. Polyurethane hard segments with different structures were first prepared from hexamethylene di-carbamate (BHC) and different diols (butanediol, hexanediol, octanediol and decanediol). Subsequently, a series of non-isocyanate PEU were obtained by polycondensation of the polyurethane hard segments with the polyether soft segments (PTMG2000). The PEU were characterized by GPC, FT-IR, 1H NMR, DSC, WAXD, SAXS, AFM and tensile testing. The results show that the urea groups generated by the side reaction affect the degree of crystallization of hard segments by influencing the hydrogen bonding of the hard segments molecular chains. The degree of hard segment crystallization, in turn, affects the thermal and mechanical properties of the polymer. The urea group content is related to the carbon chain length of the diol used for the synthesis of hard segments. When butanediol is applied to synthesize hard segment, the hard segment of the resulting PEU is unable to crystallize. Therefore, the tensile strength and modulus of elasticity of butanediol-based PEU is lowest among three, though it possesses the highest urea group content. When longer octanediol or decanediol is applied to synthesize the hard segment, the hard segments in the resulting polyether-based polyurethane are crystallizable and the resulting PEU possesses higher tensile strength.

As a special type of glioma, multicentric glioma provides an ideal pathological model for glioma research. According to the stem-cell-origin theory, multiple lesions of multicentric glioma share the same neuro-oncological origin, both in gene level and in cell level. Although the number of studies focusing on genetic evolution in gliomas with the model of multicentric gliomas were limited, some mutations, including IDH1 mutations, TERTp mutations and PTEN deletions, are found to be at an early stage in the process of genetic aberrance during glioma evolution based on the results of these studies. This article reviews the clinical reports and genetic studies of multicentric glioma, and intends to explain the various clinical phenomena of multicentric glioma from the perspective of genetic aberrance accumulation and tumor cell evolution. The malignant degree of a glioma is determined by both the tumorigenicity of early mutant genes, and the stemness of early suffered cells.

The bio-based poly(1,3-propylene 3,6,9-trioxaundecanedioate) glycol (PPTR) was prepared by the reaction between bio-based 1,3-propanediol (bio-PDO) and 3,6,9-trioxaundecanedioic acid. The as-synthesized PPTR combined with bio-PDO was reacted with 1,6-hexamethylene diisocyanate to get a bio-based polyurethane material (PPTR-PU). The PPTR-PU film has high tensile strength (17.9 MPa) and toughness (93.7 MJ/m(3)), and it can be degraded very fast under the existence of HCl and NaOH. The mass loss is 47.8% and 68.4% after 24 h of the degradation in HCl (pH 1) and NaOH (pH 13) solution, respectively. The porcine pancreatic lipase can accelerate the hydrolysis of the film under the physiological environment, leading to an approximately 50% mass loss after 20 d of the enzymatic degradation. The results from H-1 nuclear magnetic resonance, DSC, gel permeation chromatography, and FTIR measurements reveal that the PPTR-PU chains are degraded due to the hydrolysis of ester groups in the PPTR soft segments, leading to the decrease of molecular weights and the increasing degree of hydrogen bonding. The research highlights how to design and prepare the polyurethane material with fast degradable property from bio-based resources.

A series of non-isocyanate linear high molecular weight poly(ester urethane)s (PETUs) were prepared through an environmentally-friendly route based on dimethyl carbonate, 1,6-hexanediol and 1,6-hexanediamine. In this route, the polyurethane diol was first prepared by the reaction between bis-1,6-hexamethylencarbamate (BHC) and 1,6-hexanediol. A series of polyester soft segments of polyurethane have been synthesized from the polycondensation of adipic acid and different diols, including butanediol, hexanediol, octanediol and decanediol. The subsequent polycondensation of polyurethane diol and polyester diol led to linear PETUs. The resultant polymers were characterized by GPC, FTIR, 1H-NMR, 13C-NMR, DSC, WAXD, TGA and tensile test. The results indicated that PETUs possess weight-average molecular weights higher than 1×105 and the tensile strength as high as 10 MPa. The thermal properties, crystallization behavior, microphase separation behavior and morphology were studied by DSC and AFM, and the results indicated that the degree of phase separation was affected by two factors, the crystallization and hydrogen bonding interaction between soft segment and hard segment.

In acute stroke management, time window has been rigidly used as a guide for decades and the reperfusion treatment is only available in the first few limited hours. Recently, imaging-based selection of patients has successfully expanded the treatment window out to 16 and even 24 h in the DEFUSE 3 and DAWN trials, respectively. Recent guidelines recommend the use of imaging techniques to guide therapeutic decision-making and expanded eligibility in acute ischemic stroke. A tissue window is proposed to replace the time window and serve as the surrogate marker for potentially salvageable tissue. This article reviews the evolution of time window, addresses the advantage of a tissue window in precision medicine for ischemic stroke, and discusses both the established and emerging techniques of neuroimaging and their roles in defining a tissue window. We also emphasize the metabolic imaging and molecular imaging of brain pathophysiology, and highlight its potential in patient selection and treatment response prediction in ischemic stroke.