Translational stroke research
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Partial MHC Constructs Treat Thromboembolic Ischemic Stroke Characterized by Early Immune Expansion.
Inflammation and thrombosis are tightly linked, with inflammation contributing to thromboembolism and to stroke outcome. Thromboembolism is a frequent cause of ischemic stroke; yet, the most used occlusion mouse models of experimental stroke do not effectively replicate thromboembolism. Our group recently described a novel thromboembolic mouse model of stroke that successfully occludes the middle cerebral artery with high reproducibility. ⋯ Brain and spleen tissues were harvested 24 h after thromboembolic stroke and cells immunophenotyped by flow cytometry. We observed a significant increase in neutrophils and early activated T cells in the spleen and an increase in neutrophils and activated monocytes/microglia in the ischemic cortex after thromboembolic stroke. Moreover, as was shown previously for transient MCAO models, treatment of thromboembolic stroke with partial MHC constructs significantly reduced ischemic damage indicating an equivalent effect of this immune-based therapy in the thromboembolic model that better mimics the pathophysiology of human stroke.
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Evidence of the appropriate amount of fluid intake during the first few days after acute stroke was scarce. Concerns were raised in patients with acute malignant middle cerebral infarction, who tended to have malignant brain edema later. The purpose of the study was to evaluate the effect of fluid intake on the occurrence of malignant brain edema in patients with acute middle cerebral artery infarction. ⋯ Seventy-nine patients (79/184, 43%) died. In the subgroup of patients with malignant brain edema, 39 patients (39/65, 60%) died and only 11% (7/65 patients) had favorable outcome. High amount of fluid intake in the first few days of acute middle cerebral infarction was related to the occurrence of malignant brain edema.
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Spinal cord ischemia (SCI) is a devastating complication of aortic operations. Neuromonitoring using motor evoked potentials (MEPs) is a sensitive modality to detect SCI in humans. We describe a leporine SCI model using MEPs to test pharmaceutical therapeutics and other neuroprotective adjuncts. ⋯ MEPs are influenced by inhaled anesthetics and apnea but not by hypotension alone. Propofol anesthesia provides reliable MEPs. This study provides the basis for a reproducible model of SCI to be used for novel therapeutic drug development.
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Although the association between patent foramen ovale and ischemic stroke is controversial, the evaluation for a right-to-left shunt remains part of the standard workup for cryptogenic stroke. Transthoracic and transesophageal echocardiogram (TTE and TEE) are the screening test and gold standard to evaluate for right-to-left shunt, respectively. Studies comparing TTE or TEE to transcranial Doppler (TCD) have shown that 15-25 % of patients test positive for right-to-left shunt on TCD but are negative on TTE or TEE. ⋯ Our results confirm previous reports that TCD is superior to echocardiography in the detection of right-to-left shunt. The TCD+Echo- patients were more likely to have active malignancy and findings suggestive of an extracardiac shunt. These results could lead to more comprehensive evaluation for occult malignancy or a pulmonary arteriovenous malformation, both potentially treatable etiologies of ischemic stroke.
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Early brain injury (EBI) plays a significant role in poor outcomes for subarachnoid hemorrhage (SAH) patients. Further investigations are required to characterize the cellular metabolic and related histological changes that may contribute to EBI following SAH. We investigated the image patterns of 18-fluorodeoxyglucose positron emission tomography-computed tomography ((18)FDG PET-CT) during EBI and correlated histopathological changes utilizing a rat SAH model. ⋯ Regions of decreasing SUV in SAH rats correlated with neuronal death and increased expression of HO-1. Higher (18)FDG PET SUV was evident in rats post-SAH compared to sham and control groups. Regions of decreasing SUV in SAH rats correlated with neuronal death and increased HO-1 expression as evaluated by histopathology.