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Background: Cerebral edema, a significant complication arising from acute ischemic stroke (IS), has a critical influence on morbidity and mortality. p38MAPK has been shown to promote neuronal apoptosis and brain damage. However, the role of the p38MAPK inhibitor SKF-86002 in protecting against ischemic injury and cerebral edema remains unclear., Methods: Infarct area was examined by TTC staining in middle cerebral artery occlusion (MCAO) mice. Neurological score and brain water content were evaluated. TUNEL and NeuN staining were used to assess neuronal apoptosis and the survival of neurons. Blood-brain barrier (BBB) permeability was determined by Evans blue. Double immunofluorescence staining detected the colocalization of AQP4 and CX43 in astrocytes. IHC staining revealed CX43 and AQP4 expression. EDU staining detected the proliferation of Oxygen and glucose deprivation/reoxygenation (OGD/R)-treated astrocytes. Levels of oxidative stress markers were determined using commercial kits. ELISA was used to assess the secretion of pro-inflammatory factors. RT-qPCR measured the expression of CX43, AQP4 and pro-inflammatory factors. Western blot analyzed the levels of p-p38/p38, AQP4 and CX43. Co-immunoprecipitation (Co-IP) determined the interaction between CX43 and AQP4., Results: SKF-86002 attenuated brain damage, edema, and neuronal apoptosis in MCAO mice. Astrocyte proliferation was suppressed, and oxidative stress and inflammation were alleviated by SKF-86002 treatment. SKF-86002 negatively regulated p38 signaling and the expression of AQP4 and CX43. Additionally, the expression of CX43/AQP4 within astrocytes was modulated by SKF-86002., Conclusion: In summary, SKF-86002 alleviated IS injury and cerebral edema by inhibiting astrocyte proliferation, oxidative stress and inflammation. This effect was associated with the suppression of CX43/AQP4, suggesting that SKF-86002 shows promise as a novel therapeutic approach for preventing IS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke. Despite successful recanalization, a limited subset of patients benefits from the new treatment. Human MRI studies have shown that during removal of the thrombus, a shower of microclots is released from the initial thrombus, possibly causing new ischemic lesions. The aim of the current study is to quantify tissue damage following microembolism., Materials and Methods: In a rat model, microembolism was generated by injection of a mixture of polystyrene fluorescent microspheres (15, 25 and 50 µm in diameter). The animals were killed at three time-points: day 1, 3 or 7. AMIRA and IMARIS software was used for 3D reconstruction of brain structure and damage, respectively., Conclusions: Microembolism induces ischemia, hypoxia and infarction. Infarcted areas persist, but hypoxic regions recover over time suggesting that repair processes in the brain rescue the regions at risk., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: As access to patient emboli is limited, embolus analogs (EAs) have become critical to the research of large vessel occlusion (LVO) stroke and the development of thrombectomy technology. To date, techniques for fabricating standardized human blood-derived EAs are limited in the variety of compositions, and the mechanical properties relevant to thrombectomy are not quantified., Methods: EAs were made by mixing human banked red blood cells (RBCs), plasma, and platelet concentrate in 10 different volumetric percentage combinations to mimic the broad range of patient emboli causing LVO strokes. The samples underwent histologic analysis and tensile testing to mimic the pulling action of thrombectomy devices, and were compared to patient emboli., Results: EAs had histologic compositions of 0-96% RBCs, 0.78%-92% fibrin, and 2.1%-22% platelets, which can be correlated with the ingredients using a regression model. At fracture, EAs elongated from 81% to 136%, and the ultimate tensile stress ranged from 16 to 949 kPa. These EAs' histologic compositions and tensile properties showed great similarity to those of emboli retrieved from LVO stroke patients, indicating the validity of such EA fabrication methods. EAs with lower RBC and higher fibrin contents are more extensible and can withstand higher tensile stress., Conclusions: EAs fabricated and tested using the proposed new methods provide a platform for stroke research and pre-clinical development of thrombectomy devices., Competing Interests: Declarations of Competing Interest LES is a founder of Endovascular Engineering Inc., Ann Arbor, Michigan. YL serves on the Scientific Advisory Board of this company. This company is indirectly related to this manuscript as it's developing medical devices for thrombectomy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A 25-year-old woman presented with acute onset of right hemiplegia and global aphasia with National Institutes of Health Stroke Scale score of 19. Computed tomography angiography demonstrated occlusion of the left proximal middle cerebral artery. She was thrombolysed with intravenous recombinant tissue plasminogen activator (0.6 mg/kg) within 3 hours of onset of symptoms and was taken up for mechanical thrombectomy. The retrieved specimen appeared pale white and soft; histopathologic examination revealed a papillary neoplasm composed of papillae with hyalinized cores lined by endothelium, consistent with papillary fibroelastoma of cardiac origin. Transesophageal echocardiography showed no abnormalities, which can be explained by complete embolization of the mass into the cerebral circulation. On follow-up after 5 months, the patient recovered with only minimal aphasia and no cardiac symptoms. Our experience with this case highlights the importance of histopathologic examination of the mechanical thrombectomy specimen, as it provided the only clue to the etiology of stroke., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

An 89-year-old woman with chronic atrial fibrillation, hypertension, chronic heart failure, and dementia was admitted to our hospital due to multiple small cerebral and cerebellar infarctions. Transthoracic echocardiogram revealed a floating calcified mass lesion arising from the endocardium of the posterior portion of the mitral annulus with mitral annular calcification. Furthermore, the mass had a heterogeneity of the echogenicity. The mass was diagnosed as a calcified amorphous tumor based on specific echocardiographic features. Serial echocardiograms showed shrinkage and disappearance of the mass, and magnetic resonance image revealed new infarction in the left occipital lobe. Embolization of the mass appeared to cause systemic embolism., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The mechanism of thrombus formation in Trousseau syndrome remains unclear. The purpose of this study was to investigate specific pathological findings of the thrombi in Trousseau syndrome. The authors report on 2 cases of thrombi in Trousseau syndrome from large cerebral vessels removed by endovascular therapy and compared with thrombi in atherosclerosis or cardiac embolism. The first patient, a 67-year-old man, was transferred to our hospital for sudden onset consciousness disturbance and tetraparesis. He had been diagnosed with stage IV lung cancer. The magnetic resonance (MR) angiography demonstrated basilar artery occlusion. An endovascular thrombectomy was performed. The second patient, an 84-year-old woman, was transferred to our hospital for sudden onset motor aphasia and right-sided motor weakness. She has a history of stage IV pancreatic body cancer. The MR angiography demonstrated left middle cerebral artery occlusion. An endovascular thrombectomy was performed for the floating thrombus. Macroscopic findings of retrieved thrombi were observed immediately after thrombectomy. The thrombi in Trousseau syndrome were white in color and solid against manual compression, whereas thrombi from other causes were red and fragile. In terms of microscopic findings, the thrombi in Trousseau syndrome mainly contained fibrin. On the other hand, thrombi associated with atherosclerosis or cardiac embolism had smaller area of fibrin with a considerable amount of red and white blood cells. The thrombi in Trousseau syndrome, which caused occlusion of large cerebral vessel, almost exclusively consisted of fibrin., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

We describe a 59-year-old stroke patient presented with sudden onset left side weakness and a speech disorder due to a major acute cerebral infarction in the area of the right middle cerebral artery, right posterior cerebral artery, and small infarctions in the area of the left middle and left posterior cerebral artery. For the previous month, the patient had been feeling weak and had no appetite. The patient had not been previously seriously ill. A chest x-ray showed a large mass in the upper zone of the right lung. Chest computed tomography scan and echocardiography were performed and revealed advanced lung cancer invading the left atrium. Spontaneous tumor embolism is a rare cause of stroke and should be considered in the differential diagnosis of stroke in a cancer patient. Also, sometimes stroke can be the first manifestation of advanced cancer., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: More insights in the etiopathogenesis of thrombi could be helpful in the treatment of patients with acute ischemic stroke (AIS). One of the most confident and early imaging findings of stroke includes arterial hyperdensity. The purpose of this study was to determine whether thrombi's density and length would be useful for predicting their origin., Methods: We evaluated 68 consecutive patients with AIS to correlate the presence of thrombi and their imaging features with the stroke subtype., Results: After excluding patients with small-artery occlusion mechanism and undetermined and other causes, the stroke etiologic subtypes were large-artery atherosclerosis (LAA) in 59.0% of the patients, cardioembolism in 31.0%, and cervical artery dissection (CAD) in 10.0%. CAD more often caused thrombi with the longest length and highest attenuation, while thrombi that originated from the LAA had the smallest length and lowest attenuation. The mean Hounsfield unit (HU) values of all thrombi (with and without hyperdensity) on noncontrast computed tomography were 62.4 (50.0-70.0) in CAD, 53.8 (42.0-65.0) in cardioembolism, and 48.6 (27.0-65.0) in LAA. The length measurements were 28.5 mm (12.0-52.0) in CAD, 13.7 mm (5.0-31.0) in cardioembolism, and 10.8 mm (3.0-25.0) in the LAA subtype. The minimum cutoff value of 60 HU and a length greater than 20 mm were able to discriminate the CAD thrombi with an accuracy of 86.8% and 92.6%, respectively., Conclusion: Our study findings show how important thrombus analysis is in patients with AIS. Thrombus analysis can allow early suspicion of CAD before dedicated imaging of the cervical arteries is performed., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The effect of rosuvastatin was investigated on complicated aortic arch plaque (CAP) morphology and lipid profiles in acute cerebral embolism (CE) patients with normal low-density lipoprotein-cholesterol (LDL-c) levels. Transesophageal echocardiography (TEE) studies were performed in 56 consecutive CE patients with LDL-c less than 140 mg/dL who were not taking lipid-lowering agents at baseline. CAP observed by TEE was defined as the presence of greater than 4-mm diameter, ulcerated, or mobile aortic plaque. Patients were divided into those with CAP versus without CAP (group A, n=24, age 69±8 years) and without CAP (group B, n=32, age 62±10 years). Of the 24 group A patients, 18 received 5 mg/d of rosuvastatin for 6 months and had follow-up TEE studies. In Group A, the baseline values of high-density lipoprotein-cholesterol (HDL-c) and apolipoprotein A-1 (ApoA-1) were significantly lower than in Group B (44±15 versus 55±15 mg/dL, P=.0059; 103±19 versus 137±25 mg/dL, P=.0006, respectively) and age and serum high-sensitivity C-reactive protein concentration were significantly higher (69±8 vs. 62±10 years, P=.0080; 2.34±3.05 vs. 0.67±1.00 mg/dL, P=.0054, respectively). By multivariate logistic regression analysis, ApoA-1 was shown to be an independent predictor of CAP (odds ratio=.894, 95% confidence intervals .800-.996, P=.0483). In the 18 group A patients receiving rosuvastatin for 6 months, aortic arch plaque diameter and serum LDL-c were significantly decreased (5.8±2.2 to 5.1±2.1 mm, P=.0377; 110±23 to 81±23 mg/dL, P=.0008, respectively), whereas serum HDL-c and ApoA-1 concentrations were significantly increased (42±8 to 52±9 mg/dL, P=.0002; 109±22 to 135±15 mg/dL, P=.0002, respectively). Plaques were morphologically improved in 11 patients, unchanged in 6, and worsened in 1. These data suggest that rosuvastatin improves plaque morphology concomitant with improving lipid profiles in CE patients with normal LDL-c levels., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The presence or absence of the penumbra area is important when performing reperfusion therapy in patients with acute ischemic stroke. As a predictor of this penumbra area, magnetic resonance angiography (MRA)-diffusion-weighted imaging (DWI) mismatch is attracting attention. The usefulness of MRA-DWI mismatch (MDM) using the DWI-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) in endovascular treatment (EVT) of patients with cerebral large vessel occlusion was evaluated., Methods: Of 1442 patients registered in the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Registry between July 1, 2010 and June 30, 2011 who presented to the hospital within 24 hours of the onset of acute cerebral infarction because of cerebral large vessel occlusion, 188 patients who had internal carotid artery or middle cerebral artery occlusion and achieved recanalization with EVT were included. Of these, 71 patients underwent intracranial EVT because intravenous recombinant tissue plasminogen activator therapy was ineffective. The associations between the presence or absence of MDM (MDM-positive [MDM-P], DWI-ASPECTS≥6; MDM-negative [MDM-N], DWI-ASPECTS<6) and 90-day prognosis (modified Rankin Scale [mRS]) and symptomatic intracranial hemorrhage (sICH) were examined., Results: Of the 188 patients analyzed, the time from symptom onset to admission was within 3 hours in 143 patients, 3-8 hours in 36 patients, and 8 hours or more in 9 patients. The time from the onset was within 3 hours in 118 patients in the MDM-P and 25 patients in the MDM-N cases. Favorable outcomes (mRS score≤2 at 90 days) were seen in 63 patients (53.4%) in the MDM-P group and 7 patients (28.0%) in the MDM-N group, showing a significantly more favorable clinical outcome in the MDM-P group (P=.027). The incidence of sICH was significantly lower in the MDM-P group (MDM-P group 3.4%, MDM-P group 20.0%; P=.009). The time from the onset was 3-8 hours in 29 patients in the MDM-P group and in 7 patients in the MDM-N group. Favorable outcomes were seen in 12 patients (41.4%) in the MDM-P group and 2 patients (28.6%) in the MDM-N group, with no significant difference between the 2 groups. No patients had sICH. The patients admitted 8 hours or more after the onset were all MDM-P. Five patients (55.6%) had a favorable outcome., Conclusions: This study demonstrated the safety and efficacy of EVT in MDM-P patients within 3 hours of symptom onset. Although the ratio of patients who had a favorable outcome was high in the MDM-P patients admitted 3-8 hours after the onset, the difference was not significant., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Transcatheter arterial chemoembolization (TACE) is a widely used form of therapy in advanced hepatocellular carcinoma. We report the first pathological data from an autopsy case of multiple cerebral emboli occurring during TACE., Methods: A Medline search for previous cases of cerebral embolism and TACE revealed 11 other cases., Findings: Multiple microscopic subacute infarcts were found in the cerebrum, midbrain, and cerebellum of our patient on autopsy, but no embolic material was seen. Embolic material was noted in dilated vessels throughout the fibrotic right diaphragm and in the upper lobe of the right lung. Combining the literature search with our patient, the mortality of cerebral embolism after TACE is 25% (n = 12). Intracardiac shunts were seen in 20% of the cases (n = 10). Hyperdense lesions were seen on head CT in 80% of the patients evaluated (n = 10). Chest imaging revealed infiltrate or consolidation in 60% of the cases (n = 5). Pulmonary emboli were reported in 100% of the cases (n = 8)., Conclusions: Cerebral embolism after TACE is devastating. Brain pathology supports embolization of ethiodized oil rather than DC beads as the mechanism of cerebral injury. Further pathological studies are needed to better understand the pathophysiology of this condition. Lung pathology confirmed the presence of embolic material in the distal lung, suggestive of a hepatopulmonary shunt undetectable by current modalities. Evaluation for such shunts with emerging modalities such as TCD with emboli detection may be an area of future research., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

We report a 33-year-old man with a history of chronic cannabis use who sustained myocardial infarction followed by cerebral infarction after a recent significant increase in cannabis use. This is the first case of cannabis-associated stroke of probable cardioembolic origin., (© 2012 National Stroke Association.)

Bicuspid aortic valve (BAV) is a common condition but is only rarely associated with embolic complications. We describe a 42-year-old man with recurrent posterior circulatory ischemic strokes that resulted in ataxia and cognitive impairment. Transesophageal echocardiography demonstrated a BAV with mild stenosis, moderate calcification, and a dilated ascending aorta. The degree of calcification and the valve phenotype might be important factors implicating the BAV as a rare cause of ischemic stroke., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Cardiac tumor is a rare, but clinically important source of cerebral embolism. We report a case of metastatic chondrosarcoma in the left atrium with multiple cerebral emboli. A computed tomography scan of the chest revealed a large mass in the left atrium and pulmonary vein. The patient underwent heart surgery to remove the metastatic chondrosarcoma in the left atrium, to prevent the formation of further systemic emboli and possible sudden death. The cardiac tumor resection was successful, and the patient was discharged from the hospital without any handicap. This is a rare case of metastatic cardiac tumor that was a source of emboli into the brain and was eradicated., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Body fluid biomarkers of central nervous system damage may help improve the prognostic and diagnostic accuracy in ischemic stroke. We studied 53 patients. Stroke severity and outcome was rated using the National Institutes of Health Stroke Scale and modified Rankin scale. Ferritin, S100B, and NfH were measured in cerebrospinal fluid (CSF) and serum. Infarct volume was calculated from T2W images. CSF S100B (median 1.00 ng/mL) and CSF ferritin (10.0 ng/mL) levels were elevated in patients with stroke compared with control subjects (0.62 ng/mL, P < .0001; 2.34 ng/mL, P < .0001). Serum S100B (0.09 ng/mL) was higher in patients with stroke compared with control subjects (0.01 ng/mL). CSF S100B levels were higher in patients with a cardioembolic stroke (2.88 ng/mL) than in those with small-vessel disease (0.89 ng/mL, P < .05). CSF S100B levels correlated with the National Institutes of Health Stroke Scale score on admission (R = 0.56, P < .01) and the stroke volume (R = 0.44, P = .01). CSF S100B and NfH-SMI35 levels correlated with outcome on the modified Rankin scale. CSF S100B levels were related to stroke severity and infarct volume and highest in cardioembolic stroke.