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Life
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Innovative Stroke Diagnostic and Treatment Strategies
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Innovative Stroke Diagnostic and Treatment Strategies

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 33142

Special Issue Editors

Prof. Dr. Pedro Castro

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Guest Editor
1. Department of Neurology, Centro Hospitalar Universitário São João, Porto, Portugal
2. Cardiovascular Research and Development Unit, Department of Clinical Neurosciences and Mental Health, Faculty of Medicine of University of Porto, Portugal
Interests: cerebrobascular diseases; stroke; cerebral blood flow; cerebral autoregulation; cerebral vasoreactivity; neurovascular coupling; transcranial doppler; cognitive impairment
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Elsa Azevedo

E-Mail Website
Guest Editor
1. Department of Neurology, Centro Hospitalar Universitário São João, 4200-319 Porto, Portugal
2. Cardiovascular Research and Development Unit, Department of Clinical Neurosciences and Mental Health, Faculty of Medicine of University of Porto, 4099-002 Porto, Portugal
Interests: cerebral vascular disease; cerebral hemodynamics; neurosonology

Special Issue Information

Stroke is a leading cause of morbidity and mortality worldwide. However, despite significant advances in the field of stroke treatment, such as endovascular therapy and thrombolysis, many patients still do not benefit from these achievements. As an example, it has been estimated that about half of patients submitted to highly effective revascularization treatments like mechanical thrombectomy do not gain functional autonomy in the long term.

To reduce the high burden of the disease, new approaches to diagnosis and treatment are warranted. Ultrafast diagnosis of the stroke subtypes and biomarkers can help in decision making to apply the best revascularization therapy in the rapid institution of medical therapy. This can also avoid the potential hazards of these acute pharmacological interventions. Biomarkers and imaging makers could also be used to more precisely search for stroke etiology and for optimal tailoring of preventive medicine. Another exciting topic in stroke is the possibility of using the blood–brain barrier to deliver new drugs and plastic factors to ameliorate stroke recovery, an area that links nanotechnology and in-depth biophysics and molecular discovery of top translational medicine. Lastly, vascular dementia, which is usually neglected and ill-defined on clinical grounds, remains another important manifestation of cerebrovascular disease. Through the study of the microvascular functional status of cerebral small vessels and their interaction with active neurons and astrocytes and the neurovascular unit, further insights into the disease can be found, and patient treatment can be improved.

This Special Issue aims to present the latest developments in the field, covering multiple areas of stroke from diagnosis through novel therapeutic approaches. We welcome original research, reviews, and short reports on various aspects of stroke pathophysiology, diagnosis, and treatment, such as technical reports on novel or improved experimental approaches or imaging tools for stroke.

Prof. Dr. Pedro Castro
Prof. Dr. Elsa Azevedo
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stroke
  • ishchemic stroke
  • hemorrhagic stroke
  • stem cells
  • cardioembolism
  • ultrasound
  • transcranial Doppler
  • mechanisms
  • biomarkers

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Published Papers (8 papers)

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Research

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13 pages, 859 KiB  
Article
Surgery for Coagulopathy-Related Intracerebral Hemorrhage: Craniotomy vs. Minimally Invasive Neurosurgery
by Yen-Bo Liu, Lu-Ting Kuo, Chih-Hao Chen, Woon-Man Kung, Hsin-Hsi Tsai, Sheng-Chieh Chou, Shih-Hung Yang, Kuo-Chuan Wang, Dar-Ming Lai and Abel Po-Hao Huang
Life 2021, 11(6), 564; https://doi.org/10.3390/life11060564 - 15 Jun 2021
Cited by 2 | Viewed by 2618
Abstract
Coagulopathy-related intracerebral hemorrhage (ICH) is life-threatening. Recent studies have shown promising results with minimally invasive neurosurgery (MIN) in the reduction of mortality and improvement of functional outcomes, but no published data have recorded the safety and efficacy of MIN for coagulopathy-related ICH. Seventy-five [...] Read more.
Coagulopathy-related intracerebral hemorrhage (ICH) is life-threatening. Recent studies have shown promising results with minimally invasive neurosurgery (MIN) in the reduction of mortality and improvement of functional outcomes, but no published data have recorded the safety and efficacy of MIN for coagulopathy-related ICH. Seventy-five coagulopathy-related ICH patients were retrospectively reviewed to compare the surgical outcomes between craniotomy (n = 52) and MIN (n = 23). Postoperative rebleeding rates, morbidity rates, and mortality at 1 month were analyzed. Postoperative Glasgow Outcome Scale Extended (GOSE) and modified Rankin Scale (mRS) scores at 1 year were assessed for functional outcomes. Morbidity, mortality, and rebleeding rates were all lower in the MIN group than the craniotomy group (8.70% vs. 30.77%, 8.70% vs. 19.23%, and 4.35% vs. 23.08%, respectively). The 1-year GOSE score was significantly higher in the MIN group than the craniotomy group (3.96 ± 1.55 vs. 3.10 ± 1.59, p = 0.027). Multivariable logistic regression analysis also revealed that MIN contributed to improved GOSE (estimate: 0.99650, p = 0.0148) and mRS scores (estimate: −0.72849, p = 0.0427) at 1 year. MIN, with low complication rates and improved long-term functional outcome, is feasible and favorable for coagulopathy-related ICH. This promising result should be validated in a large-scale prospective study. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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13 pages, 969 KiB  
Article
Insulin-Like Growth Factor-II and Ischemic Stroke—A Prospective Observational Study
by Daniel Åberg, N. David Åberg, Katarina Jood, Petra Redfors, Christian Blomstrand, Jörgen Isgaard, Christina Jern and Johan Svensson
Life 2021, 11(6), 499; https://doi.org/10.3390/life11060499 - 29 May 2021
Cited by 1 | Viewed by 2574
Abstract
Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised [...] Read more.
Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised ischemic stroke cases (n = 492) and controls (n = 514) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months and 2 years using the modified Rankin Scale (mRS), and additionally, survival was followed at a minimum of 7 years or until death. S-IGF-II levels were higher in IS cases both in the acute phase and at 3-month follow-up compared to controls (p < 0.05 and p < 0.01, respectively). The lowest quintile of acute s-IGF-II was, compared to the four higher quintiles, associated with an increased risk of post-stroke mortality (median follow-up 10.6 years, crude hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.56–3.49, and fully adjusted HR 1.64, 95% CI 1.02–2.61). In contrast, crude associations with poor functional outcome (mRS 3–6) lost significance after full adjustment for covariates. In conclusion, s-IGF-II was higher in IS cases than in controls, and low acute s-IGF-II was an independent risk marker of increased mortality. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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11 pages, 1231 KiB  
Article
Blood Biomarkers to Predict Long-Term Mortality after Ischemic Stroke
by Laura Ramiro, Laura Abraira, Manuel Quintana, Paula García-Rodríguez, Estevo Santamarina, Jose Álvarez-Sabín, Josep Zaragoza, María Hernández-Pérez, Xavier Ustrell, Blanca Lara, Mikel Terceño, Alejandro Bustamante and Joan Montaner
Life 2021, 11(2), 135; https://doi.org/10.3390/life11020135 - 10 Feb 2021
Cited by 12 | Viewed by 3515
Abstract
Stroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively [...] Read more.
Stroke is a major cause of disability and death globally, and prediction of mortality represents a crucial challenge. We aimed to identify blood biomarkers measured during acute ischemic stroke that could predict long-term mortality. Nine hundred and forty-one ischemic stroke patients were prospectively recruited in the Stroke-Chip study. Post-stroke mortality was evaluated during a median 4.8-year follow-up. A 14-biomarker panel was analyzed by immunoassays in blood samples obtained at hospital admission. Biomarkers were normalized and standardized using Z-scores. Multiple Cox regression models were used to identify clinical variables and biomarkers independently associated with long-term mortality and mortality due to stroke. In the multivariate analysis, the independent predictors of long-term mortality were age, female sex, hypertension, glycemia, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Independent blood biomarkers predictive of long-term mortality were endostatin > quartile 2, tumor necrosis factor receptor-1 (TNF-R1) > quartile 2, and interleukin (IL)-6 > quartile 2. The risk of mortality when these three biomarkers were combined increased up to 69%. The addition of the biomarkers to clinical predictors improved the discrimination (integrative discriminative improvement (IDI) 0.022 (0.007–0.048), p < 0.001). Moreover, endostatin > quartile 3 was an independent predictor of mortality due to stroke. Altogether, endostatin, TNF-R1, and IL-6 circulating levels may aid in long-term mortality prediction after stroke. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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14 pages, 695 KiB  
Article
MiR-10a, 27a, 34b/c, and 300 Polymorphisms are Associated with Ischemic Stroke Susceptibility and Post-Stroke Mortality
by Chang Soo Ryu, Seung Hun Oh, Kee Ook Lee, Han Sung Park, Hui Jeong An, Jeong Yong Lee, Eun Ju Ko, Hyeon Woo Park, Ok Joon Kim and Nam Keun Kim
Life 2020, 10(12), 309; https://doi.org/10.3390/life10120309 - 25 Nov 2020
Cited by 8 | Viewed by 2319
Abstract
A recent study of the ischemic stroke described the roles played by miRNAs in the downregulation of specific cell-cycle gene expression and it is thought to require the development of biomarkers for the prognostic of ischemic stroke. Here, we hypothesized that four miRNA [...] Read more.
A recent study of the ischemic stroke described the roles played by miRNAs in the downregulation of specific cell-cycle gene expression and it is thought to require the development of biomarkers for the prognostic of ischemic stroke. Here, we hypothesized that four miRNA polymorphisms (miR-10a, miR-27a, miR-34b/c, and miR-300) may affect stroke susceptibility and mortality. Blood samples were collected from 530 patients and 403 controls. Genetic polymorphisms were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and real-time PCR. We found that the miR-300 rs12894467 TC genotype and the dominant model (AOR: 2.069, p-value: 0.017; AOR: 1.931, p-value: 0.027) were significantly associated with an increased risk for the ischemic stroke subtype. In Cox proportional hazard regression models, the miR-10a rs3809783 A>T and miR-34b/c rs4938723 T>C polymorphisms were associated with the mortality rates among ischemic stroke patients. We found that a miR-300 polymorphism was associated with increased ischemic stroke susceptibility among the Korean population. Additionally, polymorphisms in miR-10a and miR-34b/c were associated with the increased or decreased mortality of ischemic stroke patients. This study marks the first report of an association between ischemic stroke and miRNA polymorphisms (miR-10aA>T, miR-27aT>C, miR-34b/cT>C, and miR-300T>C) in the Korean population. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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Review

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20 pages, 561 KiB  
Review
Acute Inflammation in Cerebrovascular Disease: A Critical Reappraisal with Focus on Human Studies
by Rafael Azevedo Dias, Leonor Dias, Elsa Azevedo and Pedro Castro
Life 2021, 11(10), 1103; https://doi.org/10.3390/life11101103 - 17 Oct 2021
Cited by 7 | Viewed by 2886
Abstract
Recent attention has been focused on the field of inflammatory biomarkers associated with vascular disorders, regarding diagnosis, prognosis, and possible therapeutical targets. In this study, we aimed to perform a comprehensive review of the literature regarding the use of inflammatory biomarkers in stroke [...] Read more.
Recent attention has been focused on the field of inflammatory biomarkers associated with vascular disorders, regarding diagnosis, prognosis, and possible therapeutical targets. In this study, we aimed to perform a comprehensive review of the literature regarding the use of inflammatory biomarkers in stroke patients. We searched studies that evaluated inflammation biomarkers associated with Cerebrovascular Disease (CVD), namely, ischemic Stroke (IS), Intracerebral Hemorrhage (ICH) and Cerebral Venous Thrombosis (CVT). As of today, neutrophil–lymphocyte ratio (NLR) seems the be the most widely studied and accepted biomarker for cerebrovascular disease due to its easy access and availability. Although demonstrated as a prognostic risk factor, in IS, ICH and CVT, its diagnostic role is still under investigation. Several other prognostic factors could be used or even combined together into a diagnostic or prognostic index. Multiple inflammatory biomarkers appear to be involved in IS, ICH, and CVT. Blood inflammatory cells, easily measured and accessible at admission may provide information regarding accurate diagnosis and prognosis. Although not yet a reality, increasing evidence exists to suggest that these may become potential therapeutic targets, likely influencing or mitigating complications of CVD and improving prognosis. Nevertheless, further larger, well-designed randomized clinical trials are still needed to follow up this hypothesis. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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17 pages, 1567 KiB  
Review
Timely and Blood-Based Multiplex Molecular Profiling of Acute Stroke
by Alexandre Dias, Isabel Silva, Inês Mendes Pinto and Luís F. Maia
Life 2021, 11(8), 816; https://doi.org/10.3390/life11080816 - 11 Aug 2021
Cited by 6 | Viewed by 3780
Abstract
Stroke is a leading cause of death and disability in the world. To address such a problem, early diagnosis and tailored acute treatment represent one of the major priorities in acute stroke care. Since the efficacy of reperfusion treatments is highly time-dependent, there [...] Read more.
Stroke is a leading cause of death and disability in the world. To address such a problem, early diagnosis and tailored acute treatment represent one of the major priorities in acute stroke care. Since the efficacy of reperfusion treatments is highly time-dependent, there is a critical need to optimize procedures for faster and more precise diagnosis. We provide a concise review of the most relevant and well-documented blood–protein biomarkers that exhibit greater potential for translational to clinical practice in stroke differential diagnosis and to differentiate ischemic stroke from hemorrhagic stroke, followed by an overview of the most recent point-of-care technological approaches to address this problem. The integration of fluid-based biomarker profiling, using point-of-care biosensors with demographic, clinical, and neuroimaging parameters in multi-dimensional clinical decision-making algorithms, will be the next step in personalized stroke care. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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20 pages, 1210 KiB  
Review
Therapeutic Nanoparticles for the Different Phases of Ischemic Stroke
by Sara Bernardo-Castro, Inês Albino, Ángela María Barrera-Sandoval, Francesca Tomatis, João André Sousa, Emanuel Martins, Susana Simões, Miguel M. Lino, Lino Ferreira and João Sargento-Freitas
Life 2021, 11(6), 482; https://doi.org/10.3390/life11060482 - 26 May 2021
Cited by 22 | Viewed by 10115
Abstract
Stroke represents the second leading cause of mortality and morbidity worldwide. Ischemic strokes are the most prevalent type of stroke, and they are characterized by a series of pathological events prompted by an arterial occlusion that leads to a heterogeneous pathophysiological response through [...] Read more.
Stroke represents the second leading cause of mortality and morbidity worldwide. Ischemic strokes are the most prevalent type of stroke, and they are characterized by a series of pathological events prompted by an arterial occlusion that leads to a heterogeneous pathophysiological response through different hemodynamic phases, namely the hyperacute, acute, subacute, and chronic phases. Stroke treatment is highly reliant on recanalization therapies, which are limited to only a subset of patients due to their narrow therapeutic window; hence, there is a huge need for new stroke treatments. Nonetheless, the vast majority of promising treatments are not effective in the clinical setting due to their inability to cross the blood-brain barrier and reach the brain. In this context, nanotechnology-based approaches such as nanoparticle drug delivery emerge as the most promising option. In this review, we will discuss the current status of nanotechnology in the setting of stroke, focusing on the diverse available nanoparticle approaches targeted to the different pathological and physiological repair mechanisms involved in each of the stroke phases. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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13 pages, 252 KiB  
Review
Update on Biomarkers Associated to Cardioembolic Stroke: A Narrative Review
by Ana Catarina Fonseca and Pedro Coelho
Life 2021, 11(5), 448; https://doi.org/10.3390/life11050448 - 17 May 2021
Cited by 12 | Viewed by 3718
Abstract
Background: In the last years, several studies were conducted that evaluated biomarkers that could be helpful for cardioembolic stroke diagnosis, prognosis, and the determination of risk of stroke recurrence. Methods: We performed a narrative review of the main studies that evaluated biomarkers related [...] Read more.
Background: In the last years, several studies were conducted that evaluated biomarkers that could be helpful for cardioembolic stroke diagnosis, prognosis, and the determination of risk of stroke recurrence. Methods: We performed a narrative review of the main studies that evaluated biomarkers related to specific cardioembolic causes: atrial fibrillation, patent foramen ovale, atrial cardiomyopathy, and left ventricular wall motion abnormalities. Results: BNP and NT-proBNP are, among all biomarkers of cardioembolic stroke, the ones that have the highest amount of evidence for their use. NT-proBNP is currently used for the selection of patients that will be included in clinical trials that aim to evaluate the use of anticoagulation in patients suspected of having a cardioembolic stroke and for the selection of patients to undergo cardiac monitoring. NT-proBNP has also been incorporated in tools used to predict the risk of stroke recurrence (ABC-stroke score). Conclusions: NT-proBNP and BNP continue to be the biomarkers most widely studied in the context of cardioembolic stroke. The possibility of using other biomarkers in clinical practice is still distant, mainly because of the low methodological quality of the studies in which they were evaluated. Both internal and external validation studies are rarely performed for most biomarkers. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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