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  • 1
    In: Translational Stroke Research, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-02), p. 72-86
    Abstract: The extracellular matrix fragment perlecan domain V is neuroprotective and functionally restorative following experimental stroke. As neurogenesis is an important component of chronic post-stroke repair, and previous studies have implicated perlecan in developmental neurogenesis, we hypothesized that domain V could have a broad therapeutic window by enhancing neurogenesis after stroke. We demonstrated that domain V is chronically increased in the brains of human stroke patients, suggesting that it is present during post-stroke neurogenic periods. Furthermore, perlecan deficient mice had significantly less neuroblast precursor cells after experimental stroke. Seven-day delayed domain V administration enhanced neurogenesis and restored peri-infarct excitatory synaptic drive to neocortical layer 2/3 pyramidal neurons after experimental stroke. Domain V’s effects were inhibited by blockade of α2β1 integrin, suggesting the importance of α2β1 integrin to neurogenesis and domain V neurogenic effects. Our results demonstrate that perlecan plays a previously unrecognized role in post-stroke neurogenesis and that delayed DV administration after experimental stroke enhances neurogenesis and improves recovery in an α2β1 integrin-mediated fashion. We conclude that domain V is a clinically relevant neuroprotective and neuroreparative novel stroke therapy with a broad therapeutic window.
    Type of Medium: Online Resource
    ISSN: 1868-4483 , 1868-601X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2541897-X
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  World Neurosurgery Vol. 120 ( 2018-12), p. 200-204
    In: World Neurosurgery, Elsevier BV, Vol. 120 ( 2018-12), p. 200-204
    Type of Medium: Online Resource
    ISSN: 1878-8750
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2530041-6
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  • 3
    In: Case Reports in Neurological Medicine, Hindawi Limited, Vol. 2019 ( 2019-07-10), p. 1-5
    Abstract: Extracorporeal membrane oxygenation (ECMO) is an important life-saving technology for patients with severe acute respiratory distress syndrome (ARDS). Unfortunately, ECMO has been traditionally contraindicated in patients with hemorrhagic neurologic diseases. The recent improvement in ECMO devices, increased utilization and experience with venovenous ECMO technologies among healthcare teams, and the use of ECMO without anticoagulation has expanded the potential populations that may benefit from ECMO. We present a case of successful utilization of venovenous ECMO for severe respiratory failure secondary to ARDS in a patient with aneurysmal subarachnoid hemorrhage and severe, episodic cerebral vasospasm. We also discuss important limitations and considerations for future successful use of ECMO in hemorrhagic stroke. This case report highlights the potential for this life-saving technology in patients with hemorrhagic stroke.
    Type of Medium: Online Resource
    ISSN: 2090-6668 , 2090-6676
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2629909-4
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. suppl_1 ( 2017-02)
    Abstract: Introduction: Change in NIH Stroke Scale from admission to discharge has been proposed as an outcome-based method of assessing quality of care in the inpatient setting. Using the Kentucky Appalachian Stroke Registry database, statistical outliers were identified as potential targets for investigation. We aimed to use the analysis of this subset of patients to identify characteristics favoring exceptionally good or poor outcome. Methods: De-identified patient data was obtained from the Kentucky Appalachian Stroke Registry for all acute ischemic stroke patients from January 1, 2013 to December 31, 2014 using discharge diagnoses. Statistical process control methodology was used to identify hospitalizations with positive or negative NIHSS change more than three standard deviations from the mean. The statistical outliers underwent manual chart review to validate the data obtained from the registry and supplement it qualitatively to identify common characteristics. Chi-square tests were conducted to assess the association between patient characteristics and being a positive or negative outlier. Results: Positive outliers were less likely to have hypertension and more likely to have received intravenous thrombolysis. Negative outliers were more likely to have carotid stenosis. Both groups were more likely to have a diagnosis of cardiac arrhythmia and to have received mechanical thrombectomy. Conclusions: Gathering registry data regarding NIHSS outliers is a feasible and potentially useful tool in understanding and improving care. The absence of hypertension may represent positive predictive recovery potential in severe stroke. Patients with significant carotid disease on presentation may be at risk of neurological decline. Furthermore, patients with large vessel occlusions undergoing thrombectomy represent a high-variance population with the greatest improvements and greatest deteriorations during inpatient hospitalization.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467823-8
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  Journal of Stroke and Cerebrovascular Diseases Vol. 27, No. 3 ( 2018-03), p. 793-800
    In: Journal of Stroke and Cerebrovascular Diseases, Elsevier BV, Vol. 27, No. 3 ( 2018-03), p. 793-800
    Type of Medium: Online Resource
    ISSN: 1052-3057
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2052957-0
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  • 6
    In: Brain Research, Elsevier BV, Vol. 1059, No. 2 ( 2005-10), p. 139-148
    Type of Medium: Online Resource
    ISSN: 0006-8993
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2005
    detail.hit.zdb_id: 1462674-3
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  Journal of Stroke and Cerebrovascular Diseases Vol. 27, No. 4 ( 2018-04), p. 900-907
    In: Journal of Stroke and Cerebrovascular Diseases, Elsevier BV, Vol. 27, No. 4 ( 2018-04), p. 900-907
    Type of Medium: Online Resource
    ISSN: 1052-3057
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2052957-0
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  • 8
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 13, No. 4 ( 2021-04), p. 395-399
    Abstract: Since 2015, mechanical thrombectomy has been the standard treatment for emergent large vessel occlusion ischemic stroke. Objective To investigate, using the previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683 ), how the protein expression of a patient’s intracranial blood during ischemic stroke compares with the protein expression of their systemic arterial blood in order to better understand and treat stroke. Methods Plasma samples from 25 subjects underwent proteomic analysis, where intracranial protein expression was compared with systemic protein levels. Data including sex, comorbidities, infarct volume, and infarct time were included for each subject. Results A majority of important proteins had a lower expression in intracranial blood than in systemic arterial blood. Proteins with the most significant changes in expression were: endopeptidase at −0.26 (p 〈 0.0001), phospholipid transfer protein (PLTP) at −0.26 (p=0.0005), uromodulin (UMOD) at −0.14 (p=0.002), ficolin-2 (FCN2) at −0.46 (p=0.005), C-C motif chemokine 19 (CCL19) at −0.51 (p 〈 0.0001), C-C motif chemokine 20 (CCL20) at −0.40 (p 〈 0.0001), fibroblast growth factor 21 at −0.37 (p=0.0002), and C-C motif chemokine (CCL23) at −0.43 (p=0.0003). Conclusions Evaluation of proteomic changes in the intravascular space of a cerebral infarct in progress in human subjects suggested that changes in proteins such PLTP, fetuin-B (FETUB), and FCN2 may be involved in atherosclerotic changes, and chemokines such as CCL23 are known to play a role in the Th2 autoimmune response. These data provide a scientific springboard for identifying clinically relevant biomarkers for diagnosis/prognosis, and targets for much needed neuroprotective/neuroreparative pharmacotherapies.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2506028-4
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. Suppl_1 ( 2021-03)
    Abstract: Introduction: Sex differences in stroke have been apparent with premenopausal females having a lower incidence of stroke with better outcomes than postmenopausal females and males. We examined sex-specific outcomes and changes in plasma proteins following emergent large vessel occlusions. The previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), clinicaltrials.gov NCT03153683, allows for analysis of plasma proteins both systemically and distal to the thrombus. Methods: Plasma samples, processed in accordance with the BACTRAC protocol, were sent to Olink to run cardiometabolic and inflammatory panels. Demographics are reported as mean±SEM. Significance determined in Prism with Mann-Whitney, t-test, or pair mixed-effect analysis. Results: We evaluated 34 subjects, 〉 18 yrs old (20 females, 14 males) enrolled in BACTRAC. There was no significant difference in age (68.9±2.7, 65.4±4.5 yrs, respectively) or comorbidities (hypertension, diabetes, cholesterolemia). Interestingly, males had a larger (p 〈 0.1) change in Modified Rankin Scale (mRS, premorbid-discharge, 3.4±1.8, 2.2±1.6, respectively) with larger infarcts (86,666±30,889 mm 3 , 36,228±10,943 mm 3 , respectively). This coincided with a lower (p 〈 0.05) CTA collateral scores for males compared to females (0.64±0.67, 1.1±0.13, respectively). 12 proteins were significantly (p 〈 0.1) higher in females, compared to males (5 proteins upregulated in both the systemic and intracranial, 3 systemic specific, and 4 intracranial specific). Males had 15 proteins significantly higher than females (3 proteins upregulated in both the systemic and intracranial, 12 systemic specific, and 0 intracranial specific). The most significant intracranial protein for females is coagulation factor XI (F11) and males is transforming growth factor beta-1 (TGFB1). Analysis of an additional 16 subjects has begun to validate the sex specific proteins. Conclusions: Unexpectedly, males have larger infarcts and less independence following large vessel occlusions in BACTRAC. We hypothesize this is due to fewer collaterals which leads to sex specific signaling patterns. Additional analysis of the plasma and subjects in BACTRAC are needed to target sex specific therapeutic.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. Suppl_1 ( 2021-03)
    Abstract: Introduction: The previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes mechanical thrombectomy to obtain tissue samples for banking. Peripheral blood proximal to the clot and intracranial blood distal from the clot were isolated. Proteomic and statistical analyses revealed normalized (intracranial-systemic) CCL19 expression was a predictor of infarct volume. Statistical modeling analyses were used determine the CCL19-associated proteomic signaling network occurring during ischemic stroke relating to infarct volume. Methods: Arterial intracranial and systemic blood samples underwent analysis for inflammatory proteins using Proximity Extension Assay (PEA) via Olink (Olink Proteomics, Boston, MA). Systemic expression was used as an internal control to normalize expression in the intracranial blood. Bivariate regression was used to examine the relationship between the intracranial normalized CCL19 expression and infarct volume. A backwards stepwise regression was then used to determine a model of predictability of infarct volume by CCL19 and associated inflammatory proteins. Results: 25 subjects ( 〉 18 yrs) with a mean infarct volume of 8,172 ± 82,284 mm 3 and mean infarct time of 513 ± 246 minutes were included in this study. Their median age was 64 (24-91) and 10 (40%) were male. 16 subjects (64%) had hypertension, 15 (60%) had BMI 〉 25, and 6 (24%) had a previous stroke. The stepwise regression model shows normalized expression of 16 proteins correlated with an increase in infarct volume (p 〈 0.005): CCL20, CXCL1, OSM, CD6, OSMR, TGF-alpha, TRANCE, CXCL10, LIF-R, CCL19, CDCP1, Flt3L, CCL23, CD244, TRAIL, NOTCH1. Conclusions: In our model, the expression of these proteins were consistently changed, though the directionality differed. LIF-R, NOTCH1, TRAIL, CD6, CCL23, TGF-alpha, and CCL20 were positively correlated, while the expressions of Flt3L, OSM, OSMR, TRANCE, CD244, CDCP1, CXCL1, CXCL10, and CCL19 were negatively correlated with infarct volume. This model depicts the proteomic signaling occurring during stroke in relationship to infarct volume, which reveals potential biomarkers and therapeutic targets for the early phase of ischemic stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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