Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n = 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P = 0.042) and lower fibrin (P = 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P = 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin.

Introduction: This multicenter, retrospective study assessed the prevalence of post-stroke cognitive impairment (PSCI) 6 months after acute ischemic stroke (AIS) and its risk factors to build a bedside early predictive model for PSCI using the Montreal Cognitive Assessment (MoCA).

As a putative marker of cerebral small vessel disease, cerebral microbleeds (CMBs) have been associated with vascular cognitive impairment. Both iron accumulation and amyloid protein precursor (APP) dysregulation are recognized as pathological hallmarks underlying the progression of CMBs, but their cross-talk is not yet understood. In this study, we found a profound increase of amyloid formation with increasing FeCl₃ treatment, and a distinct change in APP metabolism and expression of iron homeostasis proteins (ferritin, Fpn1, iron regulatory protein) was observed at the 300 uM concentration of FeCl₃. Further results revealed that extracellular iron accumulation might potentially induce binding of APP to BACE1 for amyloid formation and decrease the capability of APP/Fpn1 in mediating iron export. Our findings in this study, reflecting a probable relationship between iron dyshomeostasis and amyloid pathology, may help shed light on the underlying pathogenesis of CMBs in vascular cognitive impairment.

A part of the axonal cytoskeleton protein complex, neurofilament light chain (NF‐L) has been suggested as a pathological hallmark in various neurological disorders, including hemorrhagic stroke, vascular dementia, and cerebral small vessel disease. Neuroaxonal debris are mainly engulfed and phagocytosed by microglia, while the effects of NF‐L on microglia have not been elucidated. Ferritin heavy chain (FTH) not only reflects the age‐related status of microglia but may also be secreted into the extracellular space. After treatment of microglia with varying concentrations of NF‐L (0‐3 μg/ml), we found robust increases in the number of secretory FTH‐containing exosomes in the medium. Induction of the FTH‐containing exosomes secreted from microglia stimulates neuronal loss and membrane lipid peroxidation, as assessed by CKK8 and C11‐Bodipy^581/591, respectively. However, this oxidative stress damage was attenuated by blocking Fth1 expression. Our results suggest that NF‐L, as a biomarker of axonal injury itself, could participate in neuronal ferroptosis in a nonclassical manner by secreting FTH‐containing exosomes from microglia into the extracellular matrix.

Nomogram to Predict Poor Outcome after Mechanical Thrombectomy at Older Age and Histological Analysis of Thrombus Composition: An easy scoring system to predict the risk of poor outcome after mechanical thrombectomy among the elderly is currently not available. Therefore, we aimed to develop a nomogram for predicting the probability of negative prognosis in aged patients with acute ischemic stroke undergoing thrombectomy. In addition, we sought to investigate the association between histological thrombus composition and stroke characteristics. To this end, we prospectively studied a developed cohort using data collected from a stroke center from November 2015 to December 2019. The main outcome was functional independence, defined as a modified at 90 days following a mechanical thrombectomy. A nomogram model based on multivariate logistic models was generated. The retrieved thrombi were stained with hematoxylin and eosin and assessed according to histological composition. Our results demonstrated that was independently associated with poor outcome. A total of 304 participants completed the follow-up data to generate the nomogram model. After multivariate logistic regression, five variables remained independent predictors of outcome, including older age, hemorrhagic transformation, thrombolysis in cerebral infarction score, National Institute of Health Stroke score, and neutrophil-to-lymphocyte ratio, and were used to generate the nomogram. The area under the receiver-operating characteristic curve of the model was 0.803. The clots from elderly subjects with large-artery atherosclerosis, anterior circulation, and successful recanalization groups had a higher percentage of fibrin compared to those of younger patients. This is the first nomogram to be developed and validated in a stroke center cohort for individualized prediction of poor outcome in elderly patients after mechanical thrombectomy. Clot composition provides valuable information on the underlying pathogenesis of oxidation in older patients.

Background: The subarachnoid space is continuous with the perivascular compartment in the central nervous system. However, whether the topography and severity of enlarged perivascular spaces (EPVS) correlates with spontaneous subarachnoid hemorrhage (SAH) remains unknown. Based on the underlying arteriopathy distributions, we hypothesized that EPVS in basal ganglia (BG-EPVS) are more closely associated with aneurysmal subarachnoid hemorrhage (aSAH) than other SAH without aneurysm.Methods: Magnetic resonance imaging (MRI) scans of 271 consecutive SAH survivors with and without aneurysm were analyzed for EPVS and other markers of imaging data. In the subgroup analysis, we compared the clinical characteristics and EPVS of SAH participants with and without pre-existing known risk factors (hypertension, diabetes, and smoking history) using multivariable logistic regression.Results: Patients with aSAH (n = 195) had a higher severity of BG-EPVS and centrum semiovale EPVS (CSO-EPVS) than those without aneurysm (n = 76). Importantly, BG-EPVS predominance pattern (BG-EPVS>CSO-EPVS) only existed in aSAH survivors rather than other SAH without aneurysm. In the subgroup analysis, interestingly, we also found that a high degree of BG-EPVS showed an independent relationship with aSAH in patients without pre-existing risk factors (e.g., hypertension).Conclusion: In this cohort study, BG-EPVS predominance pattern was associated with aSAH patients compared with those without aneurysm. Moreover, BG-EPVS still showed a strong association with aSAH survivors without pre-existing vascular risk factors. Our present study suggested the BG-EPVS as a potential MRI-visible characteristic would shed light on the pathogenesis of glymphatic function at the skull base for aSAH.