Editorial (Hot Topic: Neuroprotection and Neuroregeneration in Ischemic Stroke: Emerging Treatment Strategies and Potential Molecular Targets)

2013 ◽  
Vol 14 (1) ◽  
pp. 1-2
Author(s):  
G. K. Rajanikant
Keyword(s):  
Ischemic Stroke ◽  
Treatment Strategies ◽  
Molecular Targets

scholarly journals Adjunctive cytoprotective therapies in acute ischemic stroke: a systematic review

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
I. A. Mulder ◽  
E. T. van Bavel ◽  
H. E. de Vries ◽  
J. M. Coutinho
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Nitrosative Stress ◽  
Vasogenic Edema ◽  
Treatment Strategies ◽  
Oxidative And Nitrosative Stress ◽  
Main Trial ◽  
Safety Issues ◽  
Favourable Safety Profile ◽  
Neuro Inflammation

AbstractWith the introduction of endovascular thrombectomy (EVT), a new era for treatment of acute ischemic stroke (AIS) has arrived. However, despite the much larger recanalization rate as compared to thrombolysis alone, final outcome remains far from ideal. This raises the question if some of the previously tested neuroprotective drugs warrant re-evaluation, since these compounds were all tested in studies where large-vessel recanalization was rarely achieved in the acute phase. This review provides an overview of compounds tested in clinical AIS trials and gives insight into which of these drugs warrant a re-evaluation as an add-on therapy for AIS in the era of EVT. A literature search was performed using the search terms “ischemic stroke brain” in title/abstract, and additional filters. After exclusion of papers using pre-defined selection criteria, a total of 89 trials were eligible for review which reported on 56 unique compounds. Trial compounds were divided into 6 categories based on their perceived mode of action: systemic haemodynamics, excitotoxicity, neuro-inflammation, blood–brain barrier and vasogenic edema, oxidative and nitrosative stress, neurogenesis/-regeneration and -recovery. Main trial outcomes and safety issues are summarized and promising compounds for re-evaluation are highlighted. Looking at group effect, drugs intervening with oxidative and nitrosative stress and neurogenesis/-regeneration and -recovery appear to have a favourable safety profile and show the most promising results regarding efficacy. Finally, possible theories behind individual and group effects are discussed and recommendation for promising treatment strategies are described.

A Review on Preclinical Models of Ischemic Stroke: Insights Into the Pathomechanisms and New Treatment Strategies

2021 ◽  
Vol 19 ◽  
Author(s):  
Aditya A Singh ◽  
Akash Kharwar ◽  
Manoj P. Dandekar
Keyword(s):  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Neurotrophic Factors ◽  
Treatment Strategies ◽  
Experimental Models ◽  
Cerebral Stroke ◽  
Post Stroke ◽  
Stroke Models

Background: Stroke is a serious neurovascular problem and the leading cause of disability and death worldwide. The disrupted demand to supply ratio of blood and glucose during cerebral ischemia develops hypoxic shock, and subsequently necrotic neuronal death in the affected regions. Multiple causal factors like age, sex, race, genetics, diet, and lifestyle play an important role in the occurrence as well as progression of post-stroke deleterious events. These biological and environmental factors may be contributed to vasculature variable architecture and abnormal neuronal activity. Since recombinant tissue plasminogen activator is the only clinically effective clot bursting drug, there is a huge unmet medical need for newer therapies for the treatment of stroke. Innumerous therapeutic interventions have shown promise in the experimental models of stroke but failed to translate it into clinical counterparts. Methods: Original publications regarding pathophysiology, preclinical experimental models, new targets and therapies targeting ischemic stroke have been reviewed since the 1970s. Results: We highlighted the critical underlying pathophysiological mechanisms of cerebral stroke and preclinical stroke models. We discuss the strengths and caveats of widely used ischemic stroke models, and commented on the potential translational problems. We also describe the new emerging treatment strategies, including stem cell therapy, neurotrophic factors and gut microbiome-based therapy for the management of post-stroke consequences. Results : We highlighted the critical underlying pathophysiological mechanisms of cerebral stroke and preclinical stroke models. We discuss the strengths and caveats of widely used ischemic stroke models, and commented on the potential translational problems. We also describe the new emerging treatment strategies, including stem cell therapy, neurotrophic factors and gut microbiome-based therapy for the management of post-stroke consequences. Conclusion: There are still many inter-linked pathophysiological alterations with regards to stroke, animal models need not necessarily mimic the same conditions of stroke pathology and newer targets and therapies are the need of the hour in stroke research.

Histopathological analysis of retrieved thrombi from patients with acute ischemic stroke with malignant tumors

2021 ◽  
pp. neurintsurg-2020-017195
Author(s):  
Yuko Kataoka ◽  
Kazutaka Sonoda ◽  
Jun C Takahashi ◽  
Hatsue Ishibashi-Ueda ◽  
Kazunori Toyoda ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Malignant Tumors ◽  
Characteristic Curve ◽  
Cerebral Arteries ◽  
Treatment Strategies ◽  
Area Under The Curve ◽  
Histopathological Analysis ◽  
Thrombotic Risk ◽  
Patients With Cancer ◽  
Auc Value

BackgroundThe procoagulant state in cancer increases the thrombotic risk, and underlying cancer could affect treatment strategies and outcomes in patients with ischemic stroke. However, the histopathological characteristics of retrieved thrombi in patients with cancer have not been well studied. This study aimed to assess the histopathological difference between thrombi in patients with and without cancer.MethodsWe studied consecutive patients with acute major cerebral artery occlusion who were treated with endovascular therapy between October 2010 and December 2016 in our single-center registry. The retrieved thrombi were histopathologically investigated with hematoxylin and eosin and Masson’s trichrome staining. The organization and proportions of erythrocyte and fibrin/platelet components were studied using a lattice composed of 10×10 squares.ResultsOf the 180 patients studied, 17 (8 women, age 76.5±11.5 years) had cancer and 163 (69 women, age 74.1±11.2 years) did not. Those with cancer had a higher proportion of fibrin/platelets (56.6±27.4% vs 40.1±23.9%, p=0.008), a smaller proportion of erythrocytes (42.1±28.3% vs 57.5±25.1%, p=0.019), and higher serum D-dimer levels (5.9±8.2 vs 2.4±4.3 mg/dL, p=0.005) compared with the non-cancer cases. Receiver operating characteristic curve analysis showed the cut-off ratio of fibrin/platelet components related to cancer was 55.7% with a sensitivity of 74.8%, specificity 58.8% and area under the curve (AUC) value of 0.67 (95% CI 0.53 to 0.81), and the cut-off ratio of erythrocyte components was 44.7% with a sensitivity of 71.2%, specificity 58.9% and AUC value of 0.66 (95% CI 0.51 to 0.80).ConclusionsThromboemboli of major cerebral arteries in patients with cancer were mainly composed of fibrin/platelet-rich components.

Capillary Index Score Derived from Computed Tomography Angiography as An Indicator of Collateral Flow after Acute Ischemic Stroke

2019 ◽  
Author(s):  
Shang Kai ◽  
Xiaoxing Zhang ◽  
Yuehua Li
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Treatment Strategies ◽  
Artery Occlusion ◽  
Index Score ◽  
Collateral Flow ◽  
Imaging Data ◽  
Flow Group ◽  
Cerebral Artery Occlusion

Abstract Background The capillary index score (CIS) determined from DSA is used to evaluate cerebral collateral flow in acute ischemic stroke (AIS) caused by cerebral artery occlusion. Our aim was to determine the reliability of CIS calculated from MIP-CTA images as an alternative to DSA-based CIS, as CTA is less invasive and less expensive. Methods Clinical and imaging data of 40 patients with AIS caused by cerebral artery occlusion within 6 h from symptom onset were collected. CIS was calculated from CTA and DSA images. Patients were classified into the favorable collateral flow group if CIS was ≥2 (fCIS), and into the poor collateral flow group if CIS was <2 (pCIS). Agreement between the methods was evaluated using the Kappa test. Logistic regression was performed to explore the relationship between CTA-based CIS and clinical outcomes. Results The two methods had high consistency (Kappa = 0.72), and the diagnostic accuracy of CTA for CIS classification was 87.5%. The decrease in the NIHSS score at discharge was not significantly different between the fCIS and pCIS groups according to CTA (p = 0.156), while the 90-day mRS was higher in the pCIS group (p = 0.04). High CTA-based CIS and low blood glucose at admission were significantly correlated with good outcome. Conclusion CIS calculated using CTA is as reliable as DSA-based CIS for assessing collateral flow in AIS, and is also a good predictor of clinical outcome. This index could be useful for guiding patient selection and treatment strategies for AIS.

scholarly journals Endovascular Intervention for Acute Ischemic Stroke in Light of Recent Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kenan Alkhalili ◽  
Nohra Chalouhi ◽  
Stavropoula Tjoumakaris ◽  
David Hasan ◽  
Robert M. Starke ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Treatment Strategies ◽  
Endovascular Intervention ◽  
Treatment Modalities ◽  
Efficacy And Safety ◽  
The Past ◽  
Endovascular Approach

Three recently published trials, MR RESCUE, IMS III, and SYNTHESIS Expansion, evaluating the efficacy and safety of endovascular treatment of acute ischemic stroke have generated concerns about the future of endovascular approach. However, the tremendous evolution that imaging and endovascular treatment modalities have undergone over the past several years has raised doubts about the validity of these trials. In this paper, we review the role of endovascular treatment strategies in acute ischemic stroke and discuss the limitations and shortcomings that prevent generalization of the findings of recent trials. We also provide our experience in endovascular treatment of acute ischemic stroke.

Molecular Pathways of Ischemic Stroke and Advanced Therapeutic Strategies

2018 ◽  
Vol 4 (1-2) ◽  
Author(s):  
Preeti Singh
Keyword(s):  
Ischemic Stroke ◽  
New Technologies ◽  
Treatment Strategies ◽  
Molecular Pathways ◽  
Therapeutic Approaches ◽  
Permanent Disability ◽  
Acute Cerebral Ischemia ◽  
Tremendous Progress ◽  
New Treatment

Ischemic stroke is a leading cause of death and permanent disability. This disease may affect any age group and especially in old age and pregnancy. All the responsible mechanisms are yet not completely understood. There is limited therapeutic intervention beyond prevention, yet tremendous progress in understanding cause of stroke at molecular level has been going on. A lot of advancement has occurred in the prevention and treatment of stroke during the past decade. In this review an update work of causeways of stroke and its therapeutic approaches have been discussed. The relevance of excitotoxicity (role of glutamate receptor), inflammation, ischemic penumbra, apoptosis, to delayed mechanisms and, damage and treatment strategies have been hasted out. Although the results among clinical studies, conflict regarding several experimental data of different therapies, and it may improve neurological outcome after acute cerebral ischemia. Along this several other interventions and new technologies such as stroke detector microwave helmet are being assessed and many other advanced techniques developed by researchers. Even the development of other novel and new treatment strategies (regarding molecular pathways and risk to benefit therapeutic ratio) for stroke are still required in future for better treatment.

scholarly journals Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review

2016 ◽  
Vol 9 (6) ◽  
pp. 529-534 ◽  
Author(s):  
Waleed Brinjikji ◽  
Sharon Duffy ◽  
Anthony Burrows ◽  
Werner Hacke ◽  
David Liebeskind ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Treatment Strategies ◽  
Hounsfield Unit ◽  
Large Artery ◽  
Vessel Occlusion ◽  
Stroke Etiology ◽  
Imaging Characteristics ◽  
Significant Difference

Background and purposeStudying the imaging and histopathologic characteristics of thrombi in ischemic stroke could provide insights into stroke etiology and ideal treatment strategies. We conducted a systematic review of imaging and histologic characteristics of thrombi in acute ischemic stroke.Materials and methodsWe identified all studies published between January 2005 and December 2015 that reported findings related to histologic and/or imaging characteristics of thrombi in acute ischemic stroke secondary to large vessel occlusion. The five outcomes examined in this study were (1) association between histologic composition of thrombi and stroke etiology; (2) association between histologic composition of thrombi and angiographic outcomes; (3) association between thrombi imaging and histologic characteristics; (4) association between thrombi imaging characteristics and angiographic outcomes; and (5) association between imaging characteristics of thrombi and stroke etiology. A meta-analysis was performed using a random effects model.ResultsThere was no significant difference in the proportion of red blood cell (RBC)-rich thrombi between cardioembolic and large artery atherosclerosis etiologies (OR 1.62, 95% CI 0.1 to 28.0, p=0.63). Patients with a hyperdense artery sign had a higher odds of having RBC-rich thrombi than those without a hyperdense artery sign (OR 9.0, 95% CI 2.6 to 31.2, p<0.01). Patients with a good angiographic outcome had a mean thrombus Hounsfield unit (HU) of 55.1±3.1 compared with a mean HU of 48.4±1.9 for patients with a poor angiographic outcome (mean standard difference 6.5, 95% CI 2.7 to 10.2, p<0.001). There was no association between imaging characteristics and stroke etiology (OR 1.13, 95% CI 0.32 to 4.00, p=0.85).ConclusionsThe hyperdense artery sign is associated with RBC-rich thrombi and improved recanalization rates. However, there was no association between the histopathological characteristics of thrombi and stroke etiology and angiographic outcomes.

scholarly journals New Advances in Acute Ischemic Stroke Management: Review Article

2020 ◽  
Vol 7 (2) ◽  
pp. 55-60
Author(s):  
Hossein Aghamiri ◽  
Sepideh Paybast ◽  
Behnam Safarpour Lima ◽  
Behnam Mansoori
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Web Of Science ◽  
State Of The Art ◽  
Data Extraction ◽  
Treatment Strategies ◽  
Recent Advances ◽  
The Brain ◽  
Arterial Thrombolysis

Cerebrovascular disease is the second cause of death and the sixth cause of morbidity worldwide, which will rise to fourth place by 2020. The treatment strategies for acute ischemic stroke (AIS) divided into two groups, including intravenous or intra-arterial thrombolysis and mechanical thrombectomy. Regarding growing development in the realm of diagnosis and treatment of stroke through state-of-the-art approaches, including emergent thrombectomy, there are new opportunities for investigation in this area. This is while a rough rate of 85% for strokes is occupied by, and the remained is hemorrhagic. Hence, the present study aimed to review recent advances in AIS with a focus on emergent thrombectomy. Here, we first provided the relevant history, and then the recent advances were discussed. The library data collection method was employed so that such databases as Web of Science, PubMed, and Science Direct used for data extraction. The evidence confirms the importance of emergent thrombectomy as all believe the famous statement "time is the brain." However, further investigations are required to find more strong evidence accordingly.

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