International Journal of Neuroscience

Zhang, Guisong; Luo, Weigang; Dong, Yujuan; Wang, Jinyang; Bu, Wei; Meng, Danlin; Meng, Linghui; Ren, Huiling

doi: 10.1080/00207454.2025.2597798pmid: 41345539

Abstract Objective We investigated the association between middle cerebral artery atherosclerotic plaque features and cerebral small vessel disease (CSVD) imaging markers as well as the total CSVD burden, in patients with branch atheromatous disease (BAD). Methods Plaque parameters were quantified using high-resolution magnetic resonance imaging (HR-MRI) with ImageJ software, to characterize distribution, lumen stenosis, remodeling patterns, and other relevant features. Conventional MRI assessed CSVD imaging markers and total CSVD burden. Multivariate logistic regression analysis was performed following adjustment for potential confounders. Receiver operating characteristic (ROC) curve analysis with the DeLong test assessed the predictive value of plaque features for total CSVD burden. Results Compared with the non-plaque group, the plaque group showed significantly higher proportions of severe white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and moderate-to-severe CSVD burden (p < 0.05). In multivariate analysis, the presence of plaque was an independent risk factor for WMHs (OR = 2.920), CMBs (OR = 1.995), and moderate-to-severe CSVD burden (OR = 2.853); plaque distribution was an independent risk factor for WMHs (OR = 3.367); eccentric plaques were independent risk factors for lacunar infarction (OR = 8.670) and CMBs (OR = 7.891); positive remodeling (OR = 9.285) and eccentric plaques (OR = 10.355) were independent risk factors for moderate-to-severe CSVD burden. ROC analysis demonstrated plaque vulnerability effectively predicted moderate-to-severe CSVD burden (AUC = 0.8808, p < 0.05). Conclusion In ischemic stroke patients, distinct intracranial atherosclerotic stenosis (ICAS) plaque features correlate with specific CSVD phenotypes. Vulnerable plaques not only significantly increase total CSVD burden but also effectively predict CSVD severity. These findings elucidate how ICAS influences CSVD burden progression from an HR-MRI perspective and facilitate clinical risk stratification.

Fan, Changyan; Li, Chaosheng; Sui, Chenyan; Han, Likun; Liu, Yong

doi: 10.1080/00207454.2025.2601618pmid: 41368838

Abstract Background Reliable molecular biomarkers for predicting cerebral infarction outcomes remain limited, highlighting the need for integrative approaches that bridge bioinformatic discovery with clinical validation. Objective To identify key differentially expressed genes (DEGs) prognostic for cerebral infarction and evaluate their clinical utility for risk stratification through integrated bioinformatic analysis and prospective cohort validation. Methods Functional annotation employed GO enrichment and protein-protein interaction network analysis. A prospective cohort enrolled 151 cerebral infarction patients, with peripheral blood samples subjected to qPCR analysis of candidate genes. Prognostic predictive capacity was assessed via multivariable Cox regression, Kaplan-Meier survival analysis, and ROC curve analysis with clinical follow-up data. Results Five candidate DEGs (VIM, OSM, PTGS2, SOD2, SAMSN1) were identified, enriched in inflammatory response, nitric oxide metabolism, and lipopolysaccharide response pathways. qPCR confirmed significantly elevated VIM, OSM, and PTGS2 expression in poor prognosis group (p < 0.01). Multivariable Cox regression identified VIM (HR = 4.475), OSM (HR = 2.800), and homocysteine (Hcy; HR = 1.120) as independent prognostic risk factors. Kaplan-Meier analysis demonstrated significantly reduced survival in high-expression groups (all p < 0.01). The combined model integrating VIM, OSM, and Hcy achieved superior predictive performance (AUC = 0.811; sensitivity 72.55%, specificity 78.00%, Youden’s index 0.506) compared to VIM alone (AUC = 0.760). Conclusion VIM and OSM exhibit robust bioinformatic associations and stable expression with independent prognostic value in clinical cohorts.

Ye, Feng; Ren, Nana; Fang, Haitao; Shen, Ke

doi: 10.1080/00207454.2025.2605267pmid: 41403241

Abstract Aim Symptomatic carotid artery stenosis (SCAS) patients face a high risk of ischemic stroke (IS) recurrence. This study evaluates the prognostic value of the serum lactate dehydrogenase (LDH)-to-albumin ratio (L/A) for predicting IS recurrence among SCAS patients. Methods In this retrospective study (January 2020-January 2023), 307 conservatively managed SCAS patients were stratified into non-recurrence (n = 238) and recurrence (n = 69) groups based on 24-month follow-up. Serum LDH and albumin were measured, and L/A was calculated. Relationships between L/A and plaque neovascularization-related parameters (peak intensity, AUCTC, CAS rate) were assessed using Pearson correlation. Independent risk factors were determined with multivariate Cox regression, while the predictive performance and risk stratification of L/A were evaluated with ROC and Kaplan-Meier curves. Results Significant differences existed in age, hypertension, hyperlipidemia, systolic blood pressure, low-density lipoprotein cholesterol, albumin, peak intensity, AUCTC, CAS rate, vulnerable plaques, and medication adherence between the two groups. Recurrent patients exhibited higher L/A (p < 0.005). L/A correlated positively to peak intensity (r = 0.323), AUCTC (r = 0.450), and CAS rate (r = 0.529; all p < 0.001). Hyperlipidemia, vulnerable plaques, peak intensity, CAS rate, and elevated L/A were independent risk factors for IS recurrence in SCAS patients. L/A could assist in predicting IS recurrence in SCAS patients (AUC: 0.801; sensitivity: 63.77%; specificity: 85.71%). High L/A significantly increased 2-year recurrence risk in SCAS patients. Conclusion Elevated L/A potentially aids in predicting IS recurrence in SCAS patients and correlates to plaque neovascularization.

Raza, Muhammad Liaquat; Hassan, Syed Tawassul; Fatima, Wajiha; Hyder, Noorulain; Turabee, Zoha

doi: 10.1080/00207454.2025.2610611pmid: 41457287

Abstract Persistent post-concussion symptoms can greatly affect a person’s life, thinking abilities, and their capacity to go back to normal daily tasks. This narrative review gives a detailed look at new treatments for ongoing symptoms after a concussion. It includes methods like brain stimulation, medications, and holistic approaches. We searched for information using PubMed, Embase, and Google Scholar, looking for keywords like ‘post-concussion syndrome’, ‘neuromodulation’, ‘rehabilitation’, ‘cognitive behavioral therapy’, ‘vestibular therapy’, and ‘medications. ‘This review talks about how each therapy works, the proof from clinical trials, and practical tips for using them. Methods like transcranial magnetic stimulation and transcranial direct current stimulation could help improve thinking skills and mood problems. Medicines like amantadine and zolpidem may help treat certain symptoms. Methods like aerobic exercise, balance training, and talk therapy provide overall benefits. The review also points out future areas to explore, like stem cell treatment, using virtual reality for rehab, timing treatments better, and using light therapy. This review looks at new information and trends to help doctors and researchers understand the latest ways to treat ongoing symptoms after a concussion. It also aims to guide future studies in this important field.

Xiao, Rong; Zhang, Wen

doi: 10.1080/00207454.2025.2611329pmid: 41472634

Abstract Background Intracranial Aneurysms (IA) are life-threatening cerebrovascular diseases, and their pathogenesis remains not fully understood. This study aims to systematically evaluate the causal relationship between cerebrospinal fluid (CSF) metabolites and IA through bidirectional two-sample Mendelian randomization (MR) analysis to identify potential biomarkers and therapeutic targets. Methods Using genome-wide association study data from public databases, the primary analysis was conducted with inverse variance weighting, supplemented by MR-Egger regression, weighted median, weighted mode, and simple mode. Sensitivity analyses were performed using heterogeneity tests, horizontal pleiotropy tests, and leave-one-out analyses to ensure the stability of the results. Results Forward MR analysis revealed that 1-arachidonoyl-gpc (20:4n6), 2’-deoxyuridine, 3-hydroxystachydrine, 5-hydroxyhexanoate, isobutyrylcarnitine (C4), phenylacetylglutamine, and X-10457 were protective factors for IA. In contrast, 2-hydroxybutyrate/2-hydroxyisobutyrate, arabonate/xylonate, argininosuccinate, citrate, cysteinylglycine disulfide, and isovalerate were identified as risk factors for IA. Reverse MR analysis showed a significant causal relationship between IA and changes in the concentrations of 14 CSF metabolites. Sensitivity analyses indicated the robustness of these findings. Conclusions This study, through bidirectional MR analysis, uncovered the causal relationship between CSF metabolites and IA, highlighting the significant roles of various amino acids and lipid metabolites in the pathophysiology of IA. These metabolites not only provide new insights into the mechanisms underlying IA but also present potential biomarkers and therapeutic targets, offering theoretical support for early intervention and prevention strategies for the disease.

Sahil, F. N. U.; Jairamani, Sahil; Cheema, Muhammad Rafay Shahzad; Urooba, Fnu; Ibrahim, Muhammad; Abufatima, Iman Osman; Nawaz, Ali; Sajjad, Maha; Kumar, Dheeraj

doi: 10.1080/00207454.2025.2612560pmid: 41487015

Li, Linyan; Deng, Huiming; Xu, Zhiyao; Liu, Yan; Zhang, Xianwen; Zhou, Qiang; Xiao, Bing; Liu, Hua

doi: 10.1080/00207454.2026.2614748pmid: 41510695

Abstract Background High-density lipoprotein cholesterol (HDL-C)/apolipoprotein A-1 (APOA-1) ratio has been identified as a risk factor for cardiovascular disease, cancer, and all-cause mortality. However, data related to ischemic stroke (IS) are lacking. We investigated whether the HDL-C/APOA-1 ratio was associated with 3-month functional outcome in patients with IS. Methods A retrospective analysis was performed on 674 patients with IS. The 3-month functional outcome was classified as good or poor based on the modified Rankin Scale score (mRS). Logistic regression models (unadjusted and stepwise) were performed to evaluate the correlation between HDL-C/APOA-1 ratio and outcome. Restricted cubic splines evaluated nonlinear relationships, while subgroup analyses explored effect modifications. We assessed the added predictive value of the HDL-C/APOA-1 ratio by comparing nested models using the AUC, NRI, and IDI. Results The HDL-C/APOA-1 level in the group with poor functional outcomes was higher than that in the group with good functional outcomes (0.99 ± 0.14 vs. 0.94 ± 0.10, p < 0.001). In the multivariable analysis, a higher HDL-C/APOA-1 ratio was identified as an independent factor associated with poor outcome at 3 months (OR 1.50, 95% CI:1.17–1.96, p = 0.003). The odds of poor outcome in the higher HDL-C/APOA-1 quartile increased by 2.44-fold (95% CI:1.30–4.64, p = 0.006) after adjusting for potential confounders compared to lower HDL-C/APOA-1 quartiles. In addition, multivariate-adjusted restricted cubic splines show a positive approach linear pattern of this association. Conclusion Elevated HDL-C/APOA-1 is independently associated with an increased risk of poor functional outcomes at 3-month in patients with IS.

Sharma, Khyati; Agrawal, Deepak; Gabrani, Reema

doi: 10.1080/00207454.2026.2620698pmid: 41572479

Abstract Introduction Traumatic brain injury (TBI) remains a leading cause of disability and death worldwide, with no FDA-approved therapies capable of halting or reversing secondary injury cascades. Areas covered Recent years (2020–2025) have witnessed a surge in patent activity targeting diagnostic innovations, biomarker integration, and therapeutic strategies in TBI. Diagnostic advances include multimodal platforms that combine blood-based biomarkers, imaging modalities, and physiological monitoring to enhance early detection and stratification. Biomarker-driven patents, particularly those centered on glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NfL), and p-tau, have demonstrated translational value by enabling point-of-care testing and guiding therapeutic decisions. Therapeutic patents encompass a wide range of innovations, including anti-inflammatory and antioxidant agents, metabolic and vascular stabilizers, regenerative approaches, and advanced drug delivery systems designed to bypass the blood-brain barrier. Importantly, multimodal therapeutic strategies that integrate neuroprotection, neuro-restoration, and functional recovery are gaining momentum. Expert opinion Innovations in patents, such as breath-based sensors, eye-tracking systems, and non-invasive technologies, are expanding the possibilities for rapid, point-of-care testing. On the therapeutic side, patents focusing on monoclonal antibodies, neuroactive steroids, neuroprotective peptides, and site-specific delivery systems show promise; however, most candidates are still in preclinical or early clinical stages.

Xiong, Lie; Jin, Yuting; Zhang, Jingruo; Shi, Hanqiang; Zhu, Gaofeng; Zhu, Ping; Liu, Yanlin; Luo, Kaitao

doi: 10.1080/00207454.2026.2620703pmid: 41607012

Abstract Objective: This study intends to investigate the protective impact of liproxstatin-1 against cerebral ischemia-reperfusion injury (CIRI) in rats and the corresponding underlying mechanism. Methods: CIRI rat models were constructed. Pathological changes in tissues were assessed at multiple levels, including infarct area, neuronal activity, and iron content through 2,3,5-triphenyl tetrazolium chloride (TTC) staining, Nissl staining and Prussian blue (PB) staining. The expression of oxidative damage factors and key ferroptosis-related genes was assessed by enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qPCR) or western blot (WB). Rat brain tissues were subjected to bulk RNA sequencing (bulk RNA-seq) analysis. Finally, in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) models were established, and the inhibitory effect of liproxstatin-1 on ferroptosis was identified by measuring cell viability, Fe2+ levels and lipid peroxidation. Results: In vivo experiments demonstrated that liproxstatin-1 markedly improved neurological function and neuronal pathological damage in CIRI rats, while reducing iron content and oxidative damage. Bulk RNA-seq analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the IL-17 signaling pathway, ether lipid metabolism, TNF signaling pathway and ferroptosis. Consistently, qPCR and WB results showed that liproxstatin-1 treatment increased the expression of FTH1 and GPX4, while decreasing the expression of NOX1, ACSL4, COX2 and TFR1 in rat brain tissues. In vitro experiments further demonstrated that liproxstatin-1 significantly enhanced cell viability and reduced Fe2+ and reactive oxygen species (ROS) levels. Conclusions: Liproxstatin-1 inhibits the process of ferroptosis and alleviates CIRI in rats.

Zhu, Li; Pan, Yue; Wang, Zi-Liang

doi: 10.1080/00207454.2026.2620704pmid: 41571385

Abstract Background Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlapping symptoms, complicating diagnosis. EEG-derived brain connectivity metrics, based on network neuroscience, can quantify brain network organization, but comparisons between AD and FTD using standardized EEG datasets are limited. Methods We analyzed a publicly available EEG dataset consisting of 36 AD patients, 23 FTD patients, and 29 healthy controls (HCs). Resting-state eyes-closed and eyes-open EEGs were analyzed across delta, theta, alpha, and beta bands. Phase-locking values (PLV) estimated functional connectivity between 19 electrodes, and graph-theory metrics were derived using the Brain Connectivity Toolbox. Group differences were assessed using ANOVAs with FDR correction, followed by Tukey tests. Results AD patients showed reduced global efficiency and small-worldness, especially in the alpha and beta bands under eyes-closed conditions, indicating decreased integration. FTD patients exhibited localized network disruptions in frontal and central regions, particularly reduced node degree and local efficiency at F3/F4 and Pz electrodes, suggesting region-specific dysfunction. These differences were more prominent in the eyes-closed state. Conclusion EEG graph-theory analysis revealed distinct network alterations in AD and FTD. AD showed impaired global integration and loss of small-world architecture, while FTD demonstrated region-specific disruptions. These findings suggest that EEG graph metrics may serve as cost-effective biomarkers for differentiating dementia subtypes and understanding disease-specific network dysfunction.