Association of Serum Neurofilament Light and Glial Fibrillary Acidic Protein with Cerebral Small Vessel Disease in Nondemented Middle-to-Old Aged Population

非痴呆中老年人群血清神经丝轻链和胶质纤维酸性蛋白与脑小血管病的关联

Neurofilament light chain (NfL) and brain glial fibrillary acidic protein (GFAP) are promising markers for cerebral vascular damage. We aimed to evaluate if increased serum NfL and GFAP were associated with cerebral small vessel disease (CSVD) markers among the nondemented middle-to-old aged population. We included participants from the Shunyi Study who had serum NfL and GFAP measurements. Cerebral microbleeds (CMBs), lacunes, perivascular space (PVS) white matter hyperintensities volume (WMHV), and brain parenchymal fraction (BPF) were measured. Cross-sectional and longitudinal associations between CSVD imaging markers and NfL levels were evaluated using multivariable-adjusted models. We included 848 nondemented participants (mean age: 55.5 ± 8.7 years) cross-sectionaly. Among these participants, 603 underwent longitudinal analysis, with an average follow-up time of 5.59 years (range: 4.34-7.20 years). Serum NfL was positively associated with baseline lacunes (OR = 1.40, 95% CI: 1.12-1.75) and WMHV (P < 0.001). GFAP was positively associated with WMHV (P = 0.016), while the association disappeared when including NfL simultaneously in the model. CMBs, PVS, and BPF were not associated with the biomarkers. Logitudinally, baseline NfL was significantly higher among participants with incident lacunes (OR: 1.44, 95% CI: 1.07-1.92); however, this association was attenuated and lost statistical significance after further adjustment for baseline lacune. Increased serum NfL appears to be indicative of lacunes and also the progression of lacunes among middle-to-old-age population. The association between serum NfL and CSVD image markers was less pronounced in the middle-to-old-age population than in the elderly, while GFAP did not prove to be a valuable CSVD biomarker. KEY POINTS: The association between serum NfL and CSVD was less pronounced in the middle-to-old-age population than in the elderly. Serum NfL was positively associated with lacunes (OR = 1.40, 95% CI: 1.12-1.75) and WMHV (P < 0.001). Baseline serum NfL was associated with a 44% increased risk of incident lacunes over a 5.59-year follow-up, but was attenuated after controlling for baseline lacune. Other CVSD markers, including CMBs, PVS, and BPF, showed no association with either NfL or GFAP.

神经丝轻链（NfL）和脑胶质纤维酸性蛋白（GFAP）是有前景的脑血管损伤标志物。我们旨在评估在非痴呆中老年人群中，血清NfL和GFAP升高是否与脑小血管病（CSVD）标志物相关。我们纳入了顺义研究中进行了血清NfL和GFAP检测的参与者。检测了脑微出血（CMBs）、腔隙性梗死、血管周围间隙（PVS）、脑白质高信号体积（WMHV）和脑实质分数（BPF）。使用多变量调整模型评估CSVD影像学标志物与NfL水平之间的横断面和纵向关联。我们横断面纳入了848名非痴呆参与者（平均年龄：55.5±8.7岁）。在这些参与者中，603人接受了纵向分析，平均随访时间为5.59年（范围：4.34 - 7.20年）。血清NfL与基线腔隙性梗死（优势比[OR]=1.40，95%置信区间[CI]：1.12 - 1.75）和WMHV（P < 0.001）呈正相关。GFAP与WMHV呈正相关（P = 0.016），但当模型中同时纳入NfL时，这种关联消失。CMBs、PVS和BPF与这些生物标志物无关联。纵向来看，发生腔隙性梗死的参与者基线NfL显著更高（OR：1.44，95% CI：1.07 - 1.92）；然而，在进一步调整基线腔隙性梗死后，这种关联减弱并失去统计学意义。血清NfL升高似乎提示中老年人群存在腔隙性梗死以及腔隙性梗死的进展。在中老年人群中，血清NfL与CSVD影像学标志物的关联不如老年人明显，而GFAP并未被证明是有价值的CSVD生物标志物。要点：在中老年人群中，血清NfL与CSVD的关联不如老年人明显。血清NfL与腔隙性梗死（OR = 1.40，95% CI：1.12 - 1.75）和WMHV（P < 0.001）呈正相关。基线血清NfL与5.59年随访期间腔隙性梗死发生风险增加44%相关，但在控制基线腔隙性梗死后这种关联减弱。其他CSVD标志物，包括CMBs、PVS和BPF，与NfL或GFAP均无关联。

REF: Huang XH, Gao F, Yuan J, et al. Association of Serum Neurofilament Light and Glial Fibrillary Acidic Protein with Cerebral Small Vessel Disease in Nondemented Middle-to-Old Aged Population. Transl Stroke Res. Published online May 31, 2025. doi:10.1007/s12975-025-01359-9 PMID: 40450100

Comparative Outcomes of Combined Balloon Angioplasty and Intra-arterial Calcium Channel Blockers Versus Monotherapy for Cerebral Vasospasm Management: A Systematic Review and Meta-analysis

球囊血管成形术联合动脉内钙通道阻滞剂与单一疗法治疗脑血管痉挛的对比结果：一项系统评价和荟萃分析

Aneurysmal subarachnoid hemorrhage (aSAH) often leads to cerebral vasospasm, a serious complication associated with delayed cerebral ischemia (DCI) and increased morbidity. For vasospasm management, both balloon angioplasty (BA) and intra-arterial (IA) calcium channel blockers (CCBs) are commonly used, although their combined efficacy and safety compared to monotherapy remain unclear. We conducted a systematic review and meta-analysis in accordance with Cochrane and PRISMA guidelines. Studies were included if they investigated patients with vasospasm post-aSAH treated with both BA and IA CCBs. Eight studies met inclusion criteria, comprising patients treated with BA, IA nimodipine, or IA verapamil. Combined BA with IA nimodipine significantly improved clinical outcomes compared to BA alone (OR: 0.07, 95% CI: 0.01-0.68, p = 0.02) without increasing hemorrhagic or ischemic risks. However, ischemic complications were higher with combined therapy than IA nimodipine alone (OR: 0.04, 95% CI: 0.01-0.40, p < 0.01). Combined therapy reduced retreatment rates compared to IA verapamil monotherapy (OR: 3.18, 95% CI: 1.15-8.79, p = 0.03). Our analysis indicates that combined BA and IA CCBs may improve clinical outcomes for aSAH patients with vasospasm without increasing complications compared to BA alone. However, combined therapy was associated with a significant increase in ischemic complications compared to CCB monotherapy. These findings highlight the potential role of combined therapy in select patients unresponsive to single-agent approaches and emphasize the importance of careful patient selection. Further randomized studies are necessary to confirm these findings and establish standardized guidelines for combined therapy use.

动脉瘤性蛛网膜下腔出血（aSAH）常导致脑血管痉挛，这是一种与延迟性脑缺血（DCI）相关的严重并发症，会增加发病率。在血管痉挛的治疗方面，球囊血管成形术（BA）和动脉内（IA）钙通道阻滞剂（CCBs）均常用，但与单一疗法相比，其联合应用的疗效和安全性仍不明确。我们按照 Cochr伦和PRISMA指南进行了系统评价和荟萃分析。若研究调查了aSAH后发生血管痉挛且接受BA和IA CCBs联合治疗的患者，则纳入分析。八项研究符合纳入标准，包括接受BA、IA尼莫地平或IA维拉帕米治疗的患者。与单独使用BA相比，BA联合IA尼莫地平显著改善了临床结局（优势比[OR]：0.07，95%置信区间[CI]：0.01 - 0.68，p = 0.02），且未增加出血或缺血风险。然而，与单独使用IA尼莫地平相比，联合治疗的缺血并发症发生率更高（OR：0.04，95% CI：0.01 - 0.40，p < 0.01）。与IA维拉帕米单一疗法相比，联合治疗降低了再治疗率（OR：3.18，95% CI：1.15 - 8.79，p = 0.03）。我们的分析表明，与单独使用BA相比，BA和IA CCBs联合应用可能改善aSAH血管痉挛患者的临床结局，且不增加并发症。然而，与CCB单一疗法相比，联合治疗会显著增加缺血并发症。这些发现凸显了联合治疗在对单药治疗无反应的特定患者中的潜在作用，并强调了谨慎选择患者的重要性。需要进一步的随机研究来证实这些发现，并制定联合治疗应用的标准化指南。

REF: Musmar B, Orscelik A, Roy JM, et al. Comparative Outcomes of Combined Balloon Angioplasty and Intra-arterial Calcium Channel Blockers Versus Monotherapy for Cerebral Vasospasm Management: A Systematic Review and Meta-analysis. Transl Stroke Res. Published online May 29, 2025. doi:10.1007/s12975-025-01358-w PMID: 40442512

Exploring the Efficacy and Safety of Argatroban as an Adjunct to Antiplatelet Therapy in Ischemic Stroke Patients: A Systematic Review and Meta-analysis

探索阿加曲班作为缺血性卒中患者抗血小板治疗辅助用药的有效性和安全性：一项系统评价与荟萃分析

Acute ischemic stroke (AIS) is a major cause of disability and mortality worldwide. While antiplatelet therapy is standard for secondary prevention, many patients still experience early neurological deterioration (END). Argatroban, a direct thrombin inhibitor, can potentially limit thrombus progression and improve AIS's functional outcomes. This meta-analysis assessed the efficacy and safety of argatroban in combination with single (SAPT) or dual antiplatelet therapy (DAPT) compared to antiplatelets alone. Following PRISMA guidelines, a systematic search of PubMed, Scopus, and Web of Science was conducted until January 2025. Randomized controlled trials (RCTs) and cohort studies evaluating argatroban plus antiplatelets versus antiplatelets alone in AIS patients were included. The primary outcome was a 90-day modified Rankin Score (mRS) of 0-2. Secondary outcomes included mRS 0-1 and mRS 3-5 at 90 days, END, and National Institutes of Health Stroke Scale (NIHSS) improvement, stroke recurrence, intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH), and mortality. We used the mean difference (MD) for continuous variables and odds ratio (OR) for dichotomous ones at 95% confidence intervals (CI) and a P-value of 0.05. A total of 14 studies (four RCTs and 10 cohort studies) were included. Compared to antiplatelets alone, argatroban significantly improved functional outcomes, increasing the incidence of mRS 0-2 (OR = 1.36 [95%CI: 1.05, 1.76, P = 0.02]) and mRS 0-1 (OR = 1.54 [95%CI: 1.08, 2.2, P = 0.02]) while reducing END (OR = 0.42 [95%CI: 0.21, 0.85, P = 0.02]). Argatroban was also associated with greater NIHSS score improvement (MD = - 0.52 [95%CI: - 0.89, - 0.15, P = 0.005]). No significant differences were observed in mRS 3-5, stroke recurrence, ICH, sICH, or mortality. Subgroup analysis indicated that argatroban combined with DAPT showed the greatest benefits. Argatroban combined with antiplatelet therapy improves functional recovery and reduces END without increasing bleeding risks. These findings support its use, particularly with DAPT, in mild to moderate AIS management. Further large-scale RCTs are needed to optimize dosing strategies and patient selection.

急性缺血性卒中（AIS）是全球范围内导致残疾和死亡的主要原因。虽然抗血小板治疗是二级预防的标准方案，但仍有许多患者会出现早期神经功能恶化（END）。阿加曲班是一种直接凝血酶抑制剂，有可能限制血栓进展并改善AIS患者的功能结局。本荟萃分析评估了阿加曲班联合单药抗血小板治疗（SAPT）或双联抗血小板治疗（DAPT）与单纯抗血小板治疗相比的有效性和安全性。按照PRISMA指南，对PubMed、Scopus和Web of Science进行了系统检索，检索时间截至2025年1月。纳入了评估阿加曲班联合抗血小板治疗与单纯抗血小板治疗用于AIS患者的随机对照试验（RCT）和队列研究。主要结局指标是90天改良Rankin量表（mRS）评分为0 - 2分。次要结局指标包括90天mRS评分为0 - 1分和3 - 5分、END、美国国立卫生研究院卒中量表（NIHSS）改善情况、卒中复发、颅内出血（ICH）、症状性颅内出血（sICH）和死亡率。对于连续变量，我们采用均数差（MD）；对于二分类变量，采用比值比（OR），置信区间（CI）为95%，P值设定为0.05。共纳入14项研究（4项RCT和10项队列研究）。与单纯抗血小板治疗相比，阿加曲班显著改善了功能结局，提高了mRS评分为0 - 2分的发生率（OR = 1.36 [95%CI：1.05, 1.76，P = 0.02]）和mRS评分为0 - 1分的发生率（OR = 1.54 [95%CI：1.08, 2.2，P = 0.02]），同时降低了END的发生率（OR = 0.42 [95%CI：0.21, 0.85，P = 0.02]）。阿加曲班还与NIHSS评分的更大改善相关（MD = - 0.52 [95%CI： - 0.89, - 0.15，P = 0.005]）。在mRS评分为3 - 5分、卒中复发、ICH、sICH或死亡率方面未观察到显著差异。亚组分析表明，阿加曲班联合DAPT显示出最大益处。阿加曲班联合抗血小板治疗可改善功能恢复并降低END的发生率，且不增加出血风险。这些研究结果支持在轻中度AIS的治疗中使用阿加曲班，尤其是与DAPT联合使用。需要进一步开展大规模RCT来优化给药方案和患者选择。

REF: Ahmed Y, Moawad MHED, Bahtiyarova G, et al. Exploring the Efficacy and Safety of Argatroban as an Adjunct to Antiplatelet Therapy in Ischemic Stroke Patients: A Systematic Review and Meta-analysis. Transl Stroke Res. Published online May 20, 2025. doi:10.1007/s12975-025-01357-x PMID: 40392513

Photobiomodulation Promotes Early Recovery of Olfactory Function and Modulates Neuroprotective Gene Expression in a Mouse Model of Ischemic Stroke

光生物调节促进缺血性中风小鼠模型嗅觉功能的早期恢复并调节神经保护基因表达

Ischemic stroke often leads to neurological deficits, including olfactory dysfunction, which can significantly diminish quality of life. Photobiomodulation (PBM) has emerged as a promising therapeutic strategy for enhancing post-stroke recovery, although the molecular mechanisms, particularly regarding gene expression change, are not yet fully understood. This study investigates the long-term effects of photothrombosis (PT) on olfactory function and the olfactory bulb (OB) microenvironment, with a focus on PBM's efficacy during both early and late phases. In a mouse OB PT stroke model, PBM therapy (808-nm laser, 40 J/cm2 fluence, 325 mW/cm2, 2 min daily) was applied from day 2 to day 7 post-PT. Olfactory function was monitored from pre-stroke through day 28 using the buried food test (BFT), and MRI scans were performed on days 7 and 28 to assess tissue damage. RNA sequencing (RNA-seq) and reverse transcription quantitative PCR (RT-qPCR) were conducted on day 7 to evaluate gene expression changes, with additional RT-qPCR analyses performed on day 28. PBM significantly accelerated olfactory function recovery by day 14, with full recovery maintained through day 28. Despite functional recovery, MRI results indicated persistent infarction at 28 days. RNA-seq identified upregulation of neuroprotective genes, including Gpr39 and Or4m1, following PBM treatment, suggesting enhanced gene expression related to acute-phase recovery. However, the impact of PBM on gene expression and functional recovery appeared to wane in the later stages of recovery. These findings underscore PBM's potential to enhance early-stage recovery in ischemic stroke, though its benefits may be more limited in the chronic phase.

缺血性中风常导致神经功能缺损，包括嗅觉障碍，这会显著降低生活质量。光生物调节（PBM）已成为一种有前景的促进中风后恢复的治疗策略，不过其分子机制，尤其是基因表达变化方面，尚未完全明确。本研究探究了光栓法（PT）对嗅觉功能和嗅球（OB）微环境的长期影响，重点关注PBM在早期和晚期的疗效。在小鼠嗅球PT中风模型中，于PT后第2天至第7天应用PBM治疗（808纳米激光，能量密度40焦耳/平方厘米，功率密度325毫瓦/平方厘米，每日2分钟）。从中风前至第28天使用埋藏食物测试（BFT）监测嗅觉功能，并于第7天和第28天进行磁共振成像（MRI）扫描以评估组织损伤情况。在第7天进行RNA测序（RNA-seq）和逆转录定量聚合酶链反应（RT-qPCR）以评估基因表达变化，在第28天进行额外的RT-qPCR分析。到第14天，PBM显著加速了嗅觉功能的恢复，并在第28天维持了完全恢复的状态。尽管功能有所恢复，但MRI结果显示在第28天仍存在持续性梗死。RNA-seq分析发现，PBM治疗后神经保护基因（包括Gpr39和Or4m1）上调，表明与急性期恢复相关的基因表达增强。然而，PBM对基因表达和功能恢复的影响在恢复后期似乎减弱。这些发现强调了PBM在缺血性中风早期恢复中的潜力，不过其在慢性期的益处可能较为有限。

REF: Shalaby RA, Emmanuel A, Nezhad FD, et al. Photobiomodulation Promotes Early Recovery of Olfactory Function and Modulates Neuroprotective Gene Expression in a Mouse Model of Ischemic Stroke. Transl Stroke Res. Published online May 13, 2025. doi:10.1007/s12975-025-01343-3 PMID: 40358915

Automated Emergent Large Vessel Occlusion Detection Using Viz.ai Software and Its Impact on Stroke Workflow Metrics and Patient Outcomes in Stroke Centers: A Systematic Review and Meta-analysis

使用Viz.ai软件自动检测急性大血管闭塞及其对卒中中心卒中诊疗流程指标和患者预后的影响：系统评价与Meta分析

The implementation of artificial intelligence (AI), particularly Viz.ai software in stroke care, has emerged as a promising tool to enhance the detection of large vessel occlusion (LVO) and to improve stroke workflow metrics and patient outcomes. The aim of this systematic review and meta-analysis is to evaluate the impact of Viz.ai on stroke workflow efficiency in hospitals and on patients' outcomes. Following the PRISMA guidelines, we conducted a comprehensive search on electronic databases, including PubMed, Web of Science, and Scopus databases, to obtain relevant studies until 25 October 2024. Our primary outcomes were door-to-groin puncture (DTG) time, CT scan-to-start of endovascular treatment (EVT) time, CT scan-to-recanalization time, and door-in-door-out time. Secondary outcomes included symptomatic intracranial hemorrhage (ICH), any ICH, mortality, mRS score < 2 at 90 days, and length of hospital stay. A total of 12 studies involving 15,595 patients were included in our analysis. The pooled analysis demonstrated that the implementation of the Viz.ai algorithm was associated with lesser CT scan to EVT time (SMD -0.71, 95% CI [-0.98, -0.44], p < 0.001) and DTG time (SMD -0.50, 95% CI [-0.66, -0.35], p < 0.001) as well as CT to recanalization time (SMD -0.55, 95% CI [-0.76, -0.33], p < 0.001). Additionally, patients in the post-AI group had significantly lower door-in door-out time than the pre-AI group (SMD -0.49, 95% CI [-0.71, -0.28], p < 0.001). Despite the workflow metrics improvement, our analysis did not reveal statistically significant differences in patient clinical outcomes (p > 0.05). Our results suggest that the integration of the Viz.ai platform in stroke care holds significant potential for reducing EVT delays in patients with LVO and optimizing stroke flow metrics in comprehensive stroke centers. Further studies are required to validate its efficacy in improving clinical outcomes in patients with LVO.

人工智能（AI）的应用，尤其是Viz.ai软件在卒中治疗中的应用，已成为一种有前景的工具，可增强大血管闭塞（LVO）的检测能力，改善卒中诊疗流程指标和患者预后。本系统评价和荟萃分析旨在评估Viz.ai对医院卒中诊疗流程效率和患者预后的影响。我们遵循PRISMA指南，对电子数据库（包括PubMed、Web of Science和Scopus数据库）进行了全面检索，以获取截至2024年10月25日的相关研究。我们的主要结局指标包括入院到股动脉穿刺时间（DTG）、CT扫描到开始血管内治疗（EVT）时间、CT扫描到血管再通时间以及入院到出院时间。次要结局指标包括症状性颅内出血（ICH）、任何类型的颅内出血、死亡率、90天时改良Rankin量表（mRS）评分<2以及住院时长。我们的分析共纳入了12项涉及15595名患者的研究。汇总分析表明，应用Viz.ai算法与缩短CT扫描到EVT时间（标准化均差[SMD] -0.71，95%置信区间[CI] [-0.98, -0.44]，p < 0.001）、DTG时间（SMD -0.50，95% CI [-0.66, -0.35]，p < 0.001）以及CT扫描到血管再通时间（SMD -0.55，95% CI [-0.76, -0.33]，p < 0.001）相关。此外，应用人工智能后组患者的入院到出院时间显著短于应用人工智能前组（SMD -0.49，95% CI [-0.71, -0.28]，p < 0.001）。尽管诊疗流程指标有所改善，但我们的分析并未发现患者临床结局存在统计学显著差异（p > 0.05）。我们的研究结果表明，在卒中治疗中整合Viz.ai平台对于减少LVO患者的EVT延迟以及优化综合卒中中心的卒中诊疗流程指标具有巨大潜力。需要进一步的研究来验证其在改善LVO患者临床结局方面的有效性。

REF: Sarhan K, Azzam AY, Moawad MHED, Serag I, Abbas A, Sarhan AE. Automated Emergent Large Vessel Occlusion Detection Using Viz.ai Software and Its Impact on Stroke Workflow Metrics and Patient Outcomes in Stroke Centers: A Systematic Review and Meta-analysis. Transl Stroke Res. Published online May 8, 2025. doi:10.1007/s12975-025-01354-0 PMID: 40335883

Crosstalk Between Signaling Stroke Cascade and Therapeutic Receptors PPAR-γ, ROCK, CB1R, and CB2R: From Mechanism to Therapies

信号性卒中级联反应与治疗性受体PPAR - γ、ROCK、CB1R和CB2R之间的串扰：从机制到疗法

Stroke remains a leading cause of disability and mortality worldwide, primarily due to the complex and multifaceted nature of its pathophysiology. This review aims to provide a comprehensive and mechanistic understanding of the crosstalk between key signaling pathways activated during stroke and the therapeutic potential of specific receptors: PPAR-γ, ROCK, CB1R, and CB2R. We delve into the intricate signaling cascades that occur post-stroke, including excitotoxicity, oxidative stress, and inflammation, highlighting the pivotal molecular players involved. PPAR-γ, known for its neuroprotective and anti-inflammatory properties, emerges as a critical modulator in stroke therapy. ROCK, a central component in the Rho/ROCK pathway, is implicated in vascular and neuronal damage, making its inhibition a promising therapeutic strategy. The roles of CB1R and CB2R within the endocannabinoid system are explored, with a focus on their dualistic nature in neuroprotection and neurotoxicity. The review further examines the interconnectivity of these receptors within the stroke signaling network, proposing that their synergistic modulation could enhance therapeutic outcomes. Current therapeutic approaches, including pharmacological and multi-target strategies, are critically evaluated, addressing the challenges in translating mechanistic insights into clinical practice. Additionally, the identification and utilization of biomarkers for stroke diagnosis and therapy monitoring are discussed, offering a glimpse into future prospects. Emerging therapies, novel drug developments, and personalized medicine approaches are presented as potential game-changers in stroke treatment.

中风仍然是全球致残和致死的主要原因，这主要归因于其病理生理学的复杂性和多面性。本综述旨在全面且从机制层面理解中风期间激活的关键信号通路之间的相互作用，以及特定受体（过氧化物酶体增殖物激活受体 - γ（PPAR - γ）、Rho相关卷曲螺旋形成蛋白激酶（ROCK）、1型大麻素受体（CB1R）和2型大麻素受体（CB2R））的治疗潜力。我们深入探讨中风后发生的复杂信号级联反应，包括兴奋性毒性、氧化应激和炎症，并着重介绍其中的关键分子参与者。PPAR - γ以其神经保护和抗炎特性而闻名，它在中风治疗中成为关键的调节因子。ROCK是Rho/ROCK通路的核心组成部分，与血管和神经元损伤有关，因此抑制它是一种有前景的治疗策略。我们探索了内源性大麻素系统中CB1R和CB2R的作用，重点关注它们在神经保护和神经毒性方面的双重特性。本综述还进一步研究了这些受体在中风信号网络中的相互关联性，并提出对它们进行协同调节可能会改善治疗效果。我们对当前的治疗方法（包括药理学和多靶点策略）进行了批判性评估，探讨了将机制研究成果转化为临床实践所面临的挑战。此外，我们还讨论了中风诊断和治疗监测生物标志物的识别和应用，展望了未来前景。新兴疗法、新型药物研发和个性化医疗方法被视为中风治疗领域潜在的变革因素。

REF: Potdar MB, Bhamare RP, Agrawal YO, Belgamwar AV. Crosstalk Between Signaling Stroke Cascade and Therapeutic Receptors PPAR-γ, ROCK, CB1R, and CB2R: From Mechanism to Therapies. Transl Stroke Res. Published online May 8, 2025. doi:10.1007/s12975-025-01352-2 PMID: 40338418

Efficacy of Cerebrolysin Treatment as an Add-On Therapy to Mechanical Thrombectomy in Patients with Acute Ischemic Stroke Due to Large Vessel Occlusion in Anterior Circulation: Results of a 3-Month Follow-up of a Prospective, Open Label, Single-Center Study

脑活素作为前循环大血管闭塞所致急性缺血性脑卒中患者机械取栓附加治疗的疗效：一项前瞻性、开放标签、单中心研究的3个月随访结果

This study hypothesized that Cerebrolysin, a multimodal neuroprotective agent, enhances the efficacy and safety of mechanical thrombectomy (MT) in both acute ischemic stroke (AIS) and recovery stroke phases in selected patients with good collateral status (CTA-CS 2-3) and effective recanalization (mTICI 2b-3). A single-center, prospective, open-label, single-arm study with blinded outcome assessment of 50 consecutive patients with moderate-to-severe AIS treated with MT ≤ 6 h of stroke onset followed by Cerebrolysin (30 ml iv within 8 h of onset and continued to day 21, first cycle) and in a recovery phase (between 69-90 days, second cycle) compared to 50 historical controls matched by propensity scores. Key outcomes included functional independence (mRS 0-2 at 90 days), safety endpoints, and neurological recovery (NIHSS at 24 h and 7 day post MT). Patients receiving Cerebrolysin achieved higher rates of mRS 0-2 at 90 days (68% vs. 44%, p = 0.016, OR 2.7, 95% CI 1.2-6.1; NNT: 4.2), had reduced risk of secondary ICH (14% vs. 40%, p = 0.02; RR 0.37, 95% CI 0.14-0.95), and had lower NIHSS on day 7 (median [IQR]: 3 [4] vs. 6 [9], p = 0.01). There was a significant difference in Barthel Index scores between the Cerebrolysin group and the control group at 30 days (median [IQR]: 77 [32] vs. 63 [50], p = 0.03) and at 3 months (86 [22] vs. 75 [29], p = 0.01) primarily driven by the increase in the mobility and transfer components. Multivariate analysis identified Cerebrolysin as an independent predictor of favorable outcomes at 3 months (OR 7.5, 95% CI 1.8-30.9), particularly in patients with diabetes (interaction OR 9.6, 95% CI 1.01-92). The overall mortality rates at 30 and 90 days were similar in both groups (2% vs 6% and 8% vs 12%, p > 0.1). Cerebrolysin improved functional outcomes at 90 days, accelerated neurological recovery, and reduced complications post-MT in patients with small ischemic core, good collateral circulation, and effective recanalization at baseline. These findings warrant further randomized trials to validate its efficacy and explore its long-term benefits.

本研究假设，多模式神经保护剂脑活素可提高机械取栓术（MT）在急性缺血性卒中（AIS）和恢复期卒中阶段对部分具有良好侧支循环状态（CTA - CS 2 - 3级）且有效再通（mTICI 2b - 3级）患者的疗效和安全性。这是一项单中心、前瞻性、开放标签、单臂研究，对50例在卒中发作后≤6小时接受MT治疗的中重度AIS连续患者进行了盲法结局评估，这些患者在发病后8小时内静脉注射脑活素30 ml，并持续至第21天（第一周期），在恢复期（发病后69 - 90天，第二周期）继续使用，同时与50例通过倾向评分匹配的历史对照进行比较。主要结局指标包括功能独立性（90天时改良Rankin量表[mRS]评分为0 - 2分）、安全性终点以及神经功能恢复情况（MT术后24小时和7天时的美国国立卫生研究院卒中量表[NIHSS]评分）。接受脑活素治疗的患者90天时mRS 0 - 2分的比例更高（68% vs. 44%，p = 0.016，优势比[OR] 2.7，95%置信区间[CI] 1.2 - 6.1；需治疗人数[NNT]：4.2），继发性颅内出血风险降低（14% vs. 40%，p = 0.02；相对危险度[RR] 0.37，95% CI 0.14 - 0.95），且第7天时NIHSS评分更低（中位数[四分位间距]：3 [4] vs. 6 [9]，p = 0.01）。脑活素组与对照组在30天时（中位数[四分位间距]：77 [32] vs. 63 [50]，p = 0.03）和3个月时（86 [22] vs. 75 [29]，p = 0.01）的Barthel指数评分存在显著差异，主要是由于移动和转移能力得分增加所致。多变量分析显示，脑活素是3个月时良好预后的独立预测因素（OR 7.5，95% CI 1.8 - 30.9），尤其是在糖尿病患者中（交互作用OR 9.6，95% CI 1.01 - 92）。两组在30天和90天的总体死亡率相似（2% vs. 6%和8% vs. 12%，p > 0.1）。对于基线时缺血核心较小、侧支循环良好且有效再通的患者，脑活素可改善90天时的功能结局，加速神经功能恢复，并减少MT术后并发症。这些研究结果需要进一步的随机试验来验证其疗效并探索其长期益处。

REF: Staszewski J, Dębiec A, Strilciuc S, et al. Efficacy of Cerebrolysin Treatment as an Add-On Therapy to Mechanical Thrombectomy in Patients with Acute Ischemic Stroke Due to Large Vessel Occlusion in Anterior Circulation: Results of a 3-Month Follow-up of a Prospective, Open Label, Single-Center Study. Transl Stroke Res. Published online May 6, 2025. doi:10.1007/s12975-025-01355-z PMID: 40325343

Quantitative Evaluation of Incomplete Stent Apposition in Intracranial Aneurysms Using Optical Coherence Tomography: a Porcine Model Study

利用光学相干断层扫描技术对颅内动脉瘤中支架贴壁不良进行定量评估：一项猪模型研究

Incomplete stent apposition (ISA) of intracranial stents is recognized as a significant issue in aneurysm treatment leading to in-stent thrombosis and aneurysm recurrence. Traditional imaging techniques like DSA have limitations in accurately assessing stent apposition. This study aimed to explore the efficacy of optical coherence tomography (OCT) in the detection of ISA after stent-assisted coiling (SAC) and its impact on stent endothelialization and aneurysm healing in a porcine model. Twelve healthy minipigs with surgically established common carotid artery sidewall aneurysm were utilized and treated with SAC. DSA and OCT were used immediately post-procedure and during follow-ups at 4 and 12 weeks to assess aneurysm occlusion and stent apposition. Histopathology ultimately assessed stent endothelialization and aneurysm healing. ISA distance, measured by OCT, was analyzed using logistic regression to predict the association between ISA severity and stent endothelialization outcome. OCT detected ISA sites (n = 30) in all subjects at the aneurysm neck, stent ends, and locally in the stent, with a mean ISA distance of 639.65 ± 146.82 µm immediately after the procedure. One experimental pig developed in-stent occlusion after 4 weeks, resulting in death. OCT detected residual ISAs in 54.2% (13/24) at 4 weeks, decreasing to 16.7% (4/24) at 12 weeks in the remaining 11 subjects. DSA showed complete aneurysm occlusion in the remaining subjects at 12 weeks. An ISA distance of > 600 µm was found to be associated with significantly higher rates of poor stent endothelialization at the 12-week follow-up. OCT demonstrated higher sensitivity in detecting ISA after SAC. ISA distance > 600 µm can be a critical prognostic factor, associated with poor outcomes.

颅内支架贴壁不良（ISA）被认为是动脉瘤治疗中的一个重大问题，会导致支架内血栓形成和动脉瘤复发。像数字减影血管造影（DSA）这样的传统成像技术在准确评估支架贴壁情况方面存在局限性。本研究旨在探讨光学相干断层成像（OCT）在检测支架辅助弹簧圈栓塞术（SAC）后ISA的有效性，以及其对猪模型中支架内皮化和动脉瘤愈合的影响。选用12只通过手术建立颈总动脉侧壁动脉瘤的健康小型猪，并采用SAC进行治疗。术后即刻以及在4周和12周的随访期间，使用DSA和OCT评估动脉瘤闭塞情况和支架贴壁情况。最终通过组织病理学评估支架内皮化和动脉瘤愈合情况。利用逻辑回归分析OCT测量的ISA距离，以预测ISA严重程度与支架内皮化结果之间的关联。OCT在所有受试者的动脉瘤颈部、支架两端以及支架局部检测到ISA部位（n = 30），术后即刻平均ISA距离为639.65 ± 146.82 µm。1只实验猪在4周后出现支架内闭塞，最终死亡。在其余11只受试者中，OCT检测到4周时54.2%（13/24）存在残余ISA，12周时降至16.7%（4/24）。DSA显示其余受试者在12周时动脉瘤完全闭塞。研究发现，在12周随访时，ISA距离 > 600 µm与支架内皮化不良的发生率显著升高相关。OCT在检测SAC后ISA方面显示出更高的灵敏度。ISA距离 > 600 µm可能是一个关键的预后因素，与不良预后相关。

REF: Wei Z, Ma J, Zhang Z, et al. Quantitative Evaluation of Incomplete Stent Apposition in Intracranial Aneurysms Using Optical Coherence Tomography: a Porcine Model Study. Transl Stroke Res. Published online May 4, 2025. doi:10.1007/s12975-025-01356-y PMID: 40319411