Patients with spontaneous intracerebral hemorrhage (sICH) are at high risk for venous thromboembolism (VTE), a complication strongly associated with adverse clinical outcomes. While prophylactic anticoagulation has been shown to effectively reduce VTE incidence, significant uncertainty remains regarding its safety and the optimal timing of initiation. This article comprehensively reviews key aspects including anticoagulant selection, patient eligibility, therapeutic time windows, and current clinical challenges. Research gaps persist in defining appropriate anticoagulation strategies according to drug type, initiation timing, and sICH subtypes (e.g., lobar, deep, or amyloid-related hemorrhage). Future efforts should focus on conducting large-scale, multicenter, prospective clinical trials to validate the efficacy and safety of novel anticoagulants. Concurrently, integrating machine learning to develop high-precision risk prediction models, tailoring individualized treatment approaches, and establishing multidisciplinary collaborative research frameworks are essential steps toward advancing the standardization and rationalization of prophylactic anticoagulation in patients with severe sICH.

Reliable preoperative risk stratification remains challenging for meningioma patients receiving adjuvant radiotherapy, particularly in real-world settings where complete multimodal datasets are difficult to assemble. This retrospective multicenter study developed and externally validated a multimodal artificial intelligence model integrating peritumoral multiparametric MRI and clinicopathological data to predict post-radiotherapy recurrence. A total of 250 meningioma patients treated with adjuvant radiotherapy across three neurosurgical centers were included. Preoperative T1-weighted, T2-weighted, and contrast-enhanced T1-weighted MRI were analyzed using a 2.5D ResNet-50 framework across three spatial contexts: tumor only, tumor plus 1-cm peritumoral margin, and tumor plus 2-cm peritumoral margin. The 1-cm peritumoral region provided the most transferable imaging representation and was selected for downstream modeling. Deep learning, radiomics, and clinicopathological features were evaluated alone and in late-fusion Cox models. Radiomics showed high apparent training performance but limited external generalizability, whereas deep learning features demonstrated more stable cross-center performance. The final clinical–deep learning fusion model achieved the best overall discrimination, with a mean C-index of 0.856 across cohorts, showed favorable calibration and clinical net benefit, and stratified patients into clinically distinct recurrence-risk groups. These findings support peritumoral MRI-based multimodal AI as a practical tool for recurrence risk stratification after adjuvant radiotherapy in meningioma.

CD59 is an endogenous complement inhibitor that restricts membrane attack complex formation, protecting cells from complement-dependent cytotoxicity. Dysfunctional CD59 leads to uncontrolled complement activation and contributes to the pathogenesis of various diseases, including neuromyelitis optica spectrum disorder (NMOSD), a rare inflammatory autoimmune disorder specifically targeting astrocytes. However, the mechanisms underlying the regulation of CD59 expression are complex and need to be elucidated. Here, we show that in a clinically relevant NMOSD model using female mice, astrocytic CD59 protects astrocytes from AQP4-IgG and complement-mediated attacks. Through secretome and transcriptome analysis, we identified brain endothelial cell-derived SPARC as an inhibitor of VEGFA/VEGFR2 signaling, which suppresses astrocyte proliferation and CD59 production. Endothelial SPARC loss increases astrocytic CD59 and mitigates autoimmune astrocytopathy, whereas VEGFR2 activation induces CD59 and alleviates disease. Collectively, this study reveals how endothelial SPARC regulates astrocytic CD59 expression, promoting autoimmune astrocytopathy and providing a potential avenue for astrocyte-targeted therapies in NMOSD.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disorder of the central nervous system (CNS) that shares clinical features with multiple sclerosis (MS) but typically manifests with more severe symptoms. The presence of pathogenic IgG autoantibodies targeting aquaporin-4 (AQP4) channels on astrocytes serves as a highly specific biomarker that distinguishes NMOSD from MS. Unlike MS, NMOSD is characterized by profound astrocytic destruction and exhibits a distinct response to therapies. Notably, disease-modifying therapies (DMTs) effective in MS, including natalizumab, interferon-β, and fingolimod, not only fail to benefit NMOSD patients but may also exacerbate disease progression. The precise molecular mechanisms underlying this immunomodulator-induced exacerbation, however, remain not yet fully elucidated. Here, we demonstrate that natalizumab alleviated experimental autoimmune encephalomyelitis (EAE) while exacerbating the autoimmune astrocytopathy in an “EAE-NMOSD” mouse model, a phenomenon associated with a reduction in actively proliferating astrocytes. Through molecular and signaling pathway analyses, we identify that endothelial-derived vascular cell adhesion molecule 1 (VCAM1) activates astrocytes via integrin α4 signaling, thereby mitigating astrocytopathy in NMOSD-like mice. Furthermore, astrocyte-specific integrin α4 deficiency exacerbates astrocytopathy, and notably, natalizumab-induced disease exacerbation does not occur in integrin α4-conditional knockout (CKO) mice. Finally, pharmacological activation of astrocytes rescues natalizumab-induced damage and ameliorates demyelination in NMOSD-like mice. Collectively, our findings provide mechanistic gaps regarding the clinical phenomenon underlying natalizumab-induced NMOSD exacerbation and suggest astrocyte-targeted therapeutic strategies as a potential intervention for NMOSD.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction induced by sepsis, characterized by high mortality and frequent long-term cognitive impairment. Its pathogenesis involves multiple mechanisms, including endothelial activation, blood-brain barrier (BBB) disruption, neuroinflammation, and neurotransmitter imbalance, ultimately resulting in neuronal and glial injury. Recent advances in neuroimaging have provided new insights into the pathological features of SAE, while offering valuable tools for early diagnosis, prognostic stratification, and the identification of potential therapeutic targets. This Review summarizes recent advances in neuroimaging research in SAE, integrating clinical findings with pathophysiological and experimental evidence to delineate imaging phenotypes, elucidate underlying mechanisms, and highlight the translational potential of emerging imaging modalities.

Meningioma is the most common intracranial tumor. Sometimes, meningiomas can develop malignant transformation (MT). In this review, we review the incidence of MT of meningiomas. The incidence of MT of grade 2 meningiomas is likely to be higher than benign meningiomas. Approximately 1% to 4% of WHO Grade 1 meningiomas may undergo MT, while about 26% to 33% of Grade 2 meningiomas experience MT. Time to MT of grade 2 meningiomas seemed to be shorter than MT of grade 1 meningiomas. The time for Grade I meningiomas to undergo MT is approximately 5 years, while Grade II meningiomas typically experience MT in about 3 years. Several risk factors may be associated with MT, including non-skull base location, high mitotic Index, a larger primary tumor size, shorter recurrence time interval and male. Potential molecular mechanisms of MT include chromosomal abnormalities (Chromosome 22q deletion, NF2 gene mutation, loss of chromosome 1p), genomic alterations (FOXM1, CDKN2A/B and TERTp), and meningioma cancer stem cells. Secondary meningiomas may have poor tumor control rates and overall survival rates than primary meningiomas. Besides, the role of radiotherapy in MT of meningiomas is unclear. Major concerns are whether radiotherapy can induce MT of meningiomas, and whether radiotherapy can prolong time to MT through long term control of meningiomas. This review summarizes the MT of meningiomas, and may provide the direction for further study of meningiomas.

This article proposes a wearable system for rapid response during acute hypertension. The system consists of a flexible electrode patch and a signal acquisition module, which is designed for real-time monitoring of photoelectric volume pulse graph (PPG), electrocardiogram (ECG), and bioelectrical impedance (Bio-Z). The flexible patch and miniaturized signal acquisition module provide comfort to the users while maintaining stable contact with human chest skin, and successfully collects three physiological signals, demonstrating its potential application in the healthcare field. In addition, this article introduces a lightweight and effective method based on PPG signal trend components for acute hypertension monitoring, whose effectiveness is verified with animal experiments. As a result, the system reveals a response time of less than 10 s. For the blood pressure rising stage, a mean absolute error (MAE) of 3.34 mmHg between the PPG-based value and the average blood pressure is achieved. For the blood pressure declining stage, an MAE of 2.42 mmHg between the PPG-based value and the average blood pressure is achieved. The results demonstrate a strong correlation between the PPG signal trend components and the blood pressure during acute hypertension monitoring.

OBJECTIVE:The aim of this study was to investigate the relationship between the clinical and radiological characteristics of olfactory groove meningiomas (OGMs) and their molecular profiles. METHODS:The authors performed targeted next-generation and whole-genome sequencing in 123 OGM samples collected from 4 international institutions, focusing on known meningioma-driver genes. They compared the molecular data with the clinical and radiographic features of the tumors. Patient and tumor data, including age, sex, radiological features, and overall survival, were retrospectively collected and analyzed. RESULTS:The study cohort comprised 90 females (73%) and 33 males (27%), with a median age at diagnosis of 57 years (range 25-87 years). The majority of tumors (88.6%, n = 109) were classified as WHO grade I meningioma. Known driver mutations were found in 86.2% of patients (n = 106), with the most common mutations found in the SMOL412F/W535L and AKT1E17K genes, each present in 36 cases (29.3%), followed by mutations in PIK3CA/PIK3R1 (19 cases, 15.4%; 14 PIK3CA and 5 PIK3R1), TRAF7 alone (7 cases, 5.7%), POLR2AQ403K (4 cases, 3.3%), and TRAF7/KLF4K409Q (3 cases, 2.4%), while 17 patients (13.8%) did not harbor known meningioma driver mutations (wildtype group). Within molecular subgroups, patients with AKT1 mutations were the youngest (median age 51 years, range 30-87 years) and patients with TRAF7-only mutations were the oldest (median 66 years, range 28-76 years). The median tumor volume at diagnosis was 18.04 cm3. SMO-mutant tumors were significantly larger (median volume 19.5 cm3) than both AKT1-mutant (median 7.5 cm3, p = 0.021) and TRAF7/KLF4-mutant (median 4.9 cm3, p = 0.002) tumors. Tumor-associated hyperostosis of the sphenoid planum was common (58.5%), led by PIK3CA/PIK3R1, SMO, and wildtype groups (73.7%, 72.2%, and 70.6%, respectively), compared with a notably lower rate in AKT1-mutant tumors (25%) (p < 0.001). Tumor invasion of the ethmoid sinuses occurred most frequently in the TRAF7-only mutant OGMs (42.9%), followed by PIK3CA/PIK3R1-mutant (31.6%) and wildtype (23.5%) OGMs. The mean progression-free survival (PFS) was 144.4 months (95% CI 123.8-165 months). Patients with SMO-mutant OGMs exhibited a significantly shorter mean PFS of 92.0 months (95% CI 70.1-113.9 months) compared with 158.2 months (95% CI 134.9-181.5 months) for SMO-wildtype OGMs (p = 0.004), identifying a tumor type that might benefit from adjuvant treatment after resection. CONCLUSIONS:This study revealed that 70% of OGMs harbor SMO, AKT1, and PIK3CA mutations, influencing tumor behavior, symptoms, and outcomes, supporting molecular profiling for personalized treatment in OGM management.

Intracranial solitary fibrous tumor (SFT) is a rare mesenchymal tumor of fibroblastic origin in the central nervous system (CNS). The 2021 WHO classification of CNS tumor has updated the entity and grading criterion of SFT. We aimed to compare the 2021 WHO grading criterion (2021-WGC) and 2016 WHO grading criterion (2016-WGC) for their value to predict prognosis and radiotherapy (RT) efficacy. This is a retrospective study involving 223 consecutive intracranial SFT patients who received tumor resection at our neurosurgical center from 2013 to 2021. Univariable and multivariable Cox regression analyses were utilized to identify prognosis-related factors and evaluate the efficacy of RT. A risk model was constructed to predict the long-term recurrence. A total of 223 SFT patients were included in this study. During a median follow-up period of 4.67 years, 80 (35.9

Radio-resistance poses a significant challenge in meningioma treatment. This study aimed to establish radio-resistant meningioma cell lines and uncover molecular mechanisms driving radio-resistance to identify potential biomarkers and therapeutic targets. Radio-resistant meningioma cell lines (IOMM-Lee-RR, CH157-RR) were developed using a progressive radiation dose (cumulative 90 Gy). Cell morphology, radiosensitivity, apoptosis, viability, migration, invasion, cell cycle, and DNA damage repair were analyzed via clonogenic assays, flow cytometry, and Western blotting. Transcriptome sequencing was performed to identify differentially expressed genes (DEGs), followed by KEGG and GO enrichment analyses. Protein-protein interaction (PPI) analysis was conducted to identify hub genes. TK1 expression was further validated in a cohort of 350 meningiomas and the GSE189672 dataset. Radio-resistant meningioma cell lines exhibited enhanced survival, reduced apoptosis, increased cell viability, and superior migratory and invasive abilities compared to parental cells. Under radiation, these cells showed G0/G1 phase accumulation and reduced G2/M phase arrest, along with enhanced DNA repair capacity, as evidenced by lower γ-H2AX expression and fewer DNA damage foci. Transcriptome analysis revealed significant enrichment in metabolic pathways, DNA repair, and cell cycle regulation. Among 34 hub genes identified, TK1 emerged as a key gene, being highly expressed in recurrent and high-grade meningiomas and positively correlated with Ki67. Analysis of the GSE189672 dataset confirmed TK1 as a poor prognostic factor associated with tumor recurrence. Radio-resistant meningioma cells exhibit enhanced DNA repair, migration, invasion, and altered cell cycle dynamics. TK1 was identified as a promising biomarker and therapeutic target for overcoming radio-resistance in meningiomas.

Psoriasis, a chronic autoimmune skin condition with significant global morbidity, badly impairs patients' quality of life. Stress has been identified as a prominent trigger for psoriasis, and effectively management of stress can ameliorate its pathological manifestations. However, the precise mechanisms by which stress influences psoriasis remain elusive. In this study, we found that mice subjected to chronic social defeat stress (CSDS) exhibit severer imiquimod (IMQ)-induced psoriasis with increased epidermal scaling, epidermal hyperplasia, number of epidermal ridges, itch, and skin inflammation than control mice. Mechanistic study reveals that CSDS leads to an elevated release of miR-let-7b, an endogenous ligand of Toll-like receptor 7 (TLR7), from the peripheral terminal of dorsal root ganglia (DRG) neurons into the skin. This process can stimulate skin-resident macrophages to release cytokines (such as IL-6 and TNF-a) and chemokines (such as MCP-1), subsequently promoting the recruitment of additional macrophages into the skin. Notably, the specific blockade of miR-let-7b in DRG neurons effectively relieve stress-induced exacerbations of psoriasis. Furthermore, intradermal injection of synthetic miR-let-7b can induce a psoriasis-like phenotype in wildtype mice, a phenomenon that can be countered by the application of a TLR7 antagonist. Additionally, microfluidic chamber coculture assays demonstrated that miR-let-7b released by DRG neurons activates macrophages via TLR7 expressed on these immune cells. Totally, this study found that stress-induced upregulation and release of miR-let-7b from DRG neurons stimulates macrophages to secrete more inflammatory cytokines and chemokines, thereby exacerbating skin inflammation and the psoriatic phenotype. These findings provide a potential therapeutic strategy targeting the miR-let-7b/TLR7 pathway to alleviate stress-induced exacerbation of psoriasis.

One of the histopathological hallmarks of neuroinflammatory diseases such as multiple sclerosis (MS) is the emergence of astrocyte reactivity. Accumulating evidence suggests that excessive glycolysis may lead to astrocyte reactivity and contribute to neuroinflammatory responses. However, the intricate mechanisms underlying astrocyte metabolic reprogramming towards glycolysis remain largely unknown. Here, we conducted in vitro experiments using primary astrocytes and in vivo studies in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS). We observed increased astrocytic expression of MCT4, a key glycolytic regulator, in EAE mice. MCT4 enhanced astrocyte reactivity through promoting glycolysis and proliferation, mediated primarily by activation of the NF-κB and c-Myc signaling pathways. Notably, we report a novel regulatory mechanism in which the E3 ubiquitin ligase TRIM7 regulates MCT4 levels via ubiquitination. In mice, blockade of astrocyte MCT4 expression by intracerebroventricular injection of lentivirus alleviated disease severity of EAE mice. The results suggest that targeting glycolysis, specifically through the inhibition of MCT4 expression, might be effective in reducing astrocyte reactivity, neuroinflammation and demyelination occurring in MS and relating neuroinflammatory diseases.

OBJECTIVE:Intracranial solitary fibrous tumor (ISFT) is a rare type of neoplasm that resembles meningioma. The authors aimed to compare the long-term postoperative outcomes between patients with ISFT and those with meningioma, and to create a model to identify patients with ISFT who are at high risk of recurrence. METHODS:A total of 187 patients with de novo ISFT and 473 patients with de novo meningioma who underwent tumor resection at a single neurosurgical center from 2013 to 2021 were included in this study. Cohorts were matched using propensity score matching (PSM). Univariate and multivariate Cox regression analyses were performed to evaluate prognostic values of clinicopathological characteristics. RESULTS:The ISFT cohort was comprised of 187 patients (106 male, mean age 46.6 years) and, after PSM, the meningioma cohort was comprised of 187 patients (95 male, mean age 49.2 years) for comparison. The survival analysis showed that the ISFT cohort had significantly worse progression-free survival (PFS) after 5 years of follow-up (p < 0.0001) compared with the meningioma cohort. No significant difference in disease-specific survival (DSS) was observed between the cohorts during the first 5 years. However, beyond 5 years, the ISFT cohort had significantly worse DSS than the meningioma cohort (p = 0.025). Further analysis of prognostic factors revealed that an age at diagnosis ≤ 57 years, Ki-67 index ≤ 6%, mitotic count ≤ 15, low WHO grade, and receiving postoperative radiation therapy (RT) were significantly associated with prolonged PFS. Moreover, age at diagnosis, mitotic count, and postoperative RT were identified as independent factors for predicting PFS. Finally, a prognostic model was constructed to identify patients with ISFT at high risk of recurrence. The model demonstrated excellent predictive performance, particularly for predicting PFS beyond 5 years after surgery. CONCLUSIONS:The long-term prognosis of patients with ISFT was significantly worse compared with that of patients with meningioma after surgery, and this was impacted by age at diagnosis, mitotic count, and undergoing postoperative RT. The prognostic model showed excellent predictive performance for identifying patients with ISFT at high risk of recurrence.

Prior studies have demonstrated therapeutic benefits of intermittent fasting (IF) in experimental autoimmune encephalomyelitis (EAE), yet they have predominantly examined prophylactic protocols or implemented short-term post-induction interventions, leaving the therapeutic window undefined and the underlying mechanisms unelucidated. Here, we systematically evaluate intermittent fasting (IF) initiated at a clinically critical juncture of 10 days post-induction (EAE_postIF), which coincides with early symptom onset, demonstrating significant attenuation of disease progression, reduced neuroinflammation, and preserved myelin integrity. Mechanistically, EAE_postIF activates a TRIB3–PERK–autophagy axis in the spinal cord, evidenced by increased ATF4, CHOP, and TRIB3 expression and suppression of mTOR signaling. In TRIB3-deficient mice, the beneficial effects of IF are partially attenuated, with clinical and histological improvements reduced relative to wild-type controls yet remaining superior to untreated cohorts. These findings establish a well-defined therapeutic window for IF intervention in neuroinflammation and identify TRIB3–PERK–autophagy signaling as a critical mediator, supporting IF as a viable metabolic strategy to complement existing MS therapies.

Meningioma represents the most common intracranial tumor in adults. However, it is rare in pediatric patients. We aimed to demonstrate the clinicopathological characteristics and long-term outcome of pediatric meningiomas (PMs). We enrolled 74 patients with intracranial PMs and analyzed their clinicopathological characteristics. Targeted next generation sequencing was used to detect alterations in meningioma relevant genes. Progression-free survival (PFS) was compared between PMs and adult meningiomas (AMs). Univariate and multivariate Cox analyses were employed to evaluate the predictive values of clinicopathological characteristics. A nomogram was constructed and its predictive accuracy evaluated. 40 females (54.1

Purpose:Radiation resistance significantly hinders the efficacy of radiotherapy for meningiomas, posing a primary obstacle. The clinical inadequacy of therapeutic drugs and radiosensitizers for treating meningiomas further exacerbates the challenge. Therefore, the aim of this study was to identify potential radiosensitizers for treating meningiomas. Methods:A high content clonogenic survival drug screening was employed to evaluate 166 FDA-approved compounds across varied concentration ranges. Cell viability, apoptosis, and radiosensitization were assessed using CCK-8 assays, Annexin V-FITC/PI assays and standard colony formation assays. Transcriptome sequencing, immunofluorescence and cell cycle experiments were conducted to assess transcriptional profile, DNA double-strand break damage and cell cycle distribution. Finally, the radiosensitizing effect of Maytansine was assessed in vivo through subcutaneous tumor implantation in nude mice. Results:The proportion of maytansine exhibiting SRF≥1.5 within the detectable concentration range was 100%. CCK-8 assay indicated the IC50 values of maytansine for IOMM-Lee and CH157 were 0.26 ± 0.06 nM and 0.31 ± 0.01 nM, respectively. Standard clonogenic survival assays and Annexin V-FITC/PI assays revealed maytansine had a notable radiosensitizing effect on meningioma cells. Transcriptome sequencing analysis demonstrated that maytansine can modulate cell cycle and DNA damage repair. Immunofluorescence analysis of γ-H2AX and cell cycle experiments demonstrated that Maytansine enhances DNA double-strand breaks and induces G2/M phase arrest. Moreover, in vivo studies had indicated that Maytansine augments the therapeutic efficacy of radiotherapy. Conclusion:This study highlighted the potential of maytansine as a potent inhibitor and radiosensitizer for meningiomas by inducing G2/M phase cell cycle arrest and enhancing DNA double-strand break damage. These findings opened up a promising path in the development of radiosensitizers aimed at treating this condition.

68Ga-DOTATATE binds to somatostatin receptors (SSTR) and is used for PET/CT imaging for diagnosing meningioma and guiding postoperative radiotherapy. However, the relationship between the clinicopathological characteristics and the imaging features of 68Ga-DOTATATE PET/CT in meningioma remains undetermined. We conducted a retrospective study at a single neurosurgical center. Semiquantitative indices of 68Ga-DOTATATE PET/CT, including maximum standardized uptake value (SUV-max), median standardized uptake value (SUV-median), mean standardized uptake value (SUV-mean), and metabolic tumor volume (MTV), were measured. The correlations between these parameters and clinicopathological characteristics were analyzed. Eighty patients were retrospectively analyzed, including 45 with WHO grade 1 meningiomas, 33 with grade 2, and 2 with grade 3. The median SUV-max value was significantly higher in meningiomas with high WHO grade (P = 0.017), positive SSTR2a expression (P = 0.023), and in male patients (P = 0.002). Bulk RNA data was available in forty patients. RNA expression of SSTR2 was significantly elevated in the SSTR2a-positive group and correlated positively with SUV-max, SUV-median, and SUV-mean. Furthermore, the high RNA scores risk group exhibited significantly higher SUV-max compared to the intermediate- and low-risk groups. Of note, an SUV-max > 15.55 (P = 0.014) was independently associated with high WHO grade. Lastly, a nomogram incorporating SUV-max, gender, and surgical history demonstrated robust performance in preoperatively identifying patients at risk for high WHO grade, offering the potential utility of 68Ga-DOTATATE PET/CT in clinical practice. SUV-max of 68Ga-DOTATATE PET/CT was significantly higher in high grade and high RNA score risk groups of meningioma. Of note, an SUV-max > 15.55 was independently associated with high WHO grade.

Hypometabolism, characterized by hypothermia and cardiovascular depression, is associated with higher mortality in patients with septic shock. However, the neural substrates underlying the hypometabolic state during systemic inflammation remain poorly understood. Here, using activity-dependent genetic labeling of neurons activated by lipopolysaccharide (LPS) administration and cecal ligation and puncture (CLP) in mice, we identified a discrete population of glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) that drives hypothermia and cardiovascular depression. Optogenetic stimulation of vlPAGvglut2 neurons induced hypothermia and cardiovascular depression in healthy mice, whereas their genetic ablation attenuated the reductions in core temperature and cardiovascular function observed during systemic inflammation. Furthermore, we demonstrated that projections from vlPAGvglut2 neurons to the nucleus tractus solitarius mediate these hypometabolic pathophysiological effects. Taken together, our findings reveal a vlPAG excitatory circuit that regulates hypometabolic responses to systemic inflammation, providing potential therapeutic targets for mitigating severe sepsis-induced hypothermia and cardiovascular dysfunction.

BACKGROUND:Sepsis-associated encephalopathy (SAE), a severe neurological disorder, is marked by widespread brain dysfunction. At present, there is no universally accepted criterion for diagnosing SAE in animal models. This study proposes a standardized evaluation method for SAE in mice, addressing inconsistencies in current research. METHOD:Using a cecal ligation and puncture (CLP) model to induce sepsis, we assessed the physiological status of mice with a modified SHIRPA score to differentiate SAE from non-SAE, validating our findings through various behavioral tests and evaluations of neuroinflammation and neuronal damage. RESULTS:Our findings revealed that the conventional mild-moderate-severe categorization of SHIRPA was insufficient for distinguishing between SAE and non-SAE. To enhance differentiation, we classified mice based on the median modified SHIRPA score, validating this approach through behavioral tests including the Y-maze, three-chamber social test, and open field test. This method effectively identified neurological impairments in septic mice. Further validation involved assessing neuronal damage, neuroinflammation, the Morris water maze, and long-term potentiation (LTP) in the hippocampal CA1 region. Results indicated that mice in the up-Median group exhibited greater neuroinflammation, neuronal injury, and cognitive deficits compared to the down-Median group. CONCLUSIONS:This study establishes a reliable evaluation method for SAE in murine models, facilitating improved differentiation between SAE and non-SAE. Such advancements will enhance our understanding of the pathogenesis of SAE and guide more effective treatment strategies.