scholarly journals Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Cesar Reis ◽  
Onat Akyol ◽  
Wing Mann Ho ◽  
Camila Araujo ◽  
Lei Huang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Molecular Mechanisms ◽  
Injury Severity ◽  
Treatment Strategies ◽  
Tissue Perfusion ◽  
Pathological Process ◽  
Acute Ischemia ◽  
Stroke Therapy ◽  
New Treatment

Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments.

Abstract TP476: White Matter Hyperintensity Burden is Associated With Poor Collateral Flow and Worse Outcomes in an Acute Ischemic Stroke Cohort

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Rami-James Assadi ◽  
Hongyu An ◽  
Yasheng Chen ◽  
Andria Ford ◽  
Jin-Moo Lee
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Pearson Correlation ◽  
Stroke Onset ◽  
White Matter Hyperintensity ◽  
Flow Index ◽  
Acute Ischemia ◽  
Collateral Flow ◽  
Core Volume

Introduction: White matter hyperintensity volume (WMHv), a quantitative neuroimaging biomarker of cerebral small vessel disease (CSVD), is associated worse outcomes after ischemic stroke. In this study, we hypothesized that worse outcomes in CSVD patients were due to poor collateral flow during acute ischemia. Methods: 47 patients with acute ischemic stroke (AIS) were prospectively enrolled in this study. Serial MRIs were performed at 3 hours and 30 days after stroke onset. 3-hour FLAIR images were used to determine WMHv, after manually delineating lesions with MIPAV. An index of collateral flow (delayed perfusion to the penumbra) was determined by subtracting core volume (volume of tissue with ADC<600) from the volume of brain tissue with Tmax>2. Patient’s NIHSS was scored at 3 hours and 30 days after stroke onset and the difference was calculated (ΔNIHSS). Log-transformed WMHv was correlated to ΔNIHSS and the collateral flow index, using Pearson correlation. Results: Mean age = 63.9 years (SD 13.5); 37% female; median 3-hour NIHSS = 13 (IQR 6.5-20); median change in NIHSS between 3h and 30d = 4 (IQR: 0-7); median core volume = 13cm3 (IQR 4.3-35.6); median WMHv = 1.257cm3 (IQR 641-3595). WMHv was associated with reduced improvement in ΔNIHSS (R=-0.42, ρ=0.005). Furthermore, WMHv demonstrated a trend for association with poor collateral flow (R=-0.28, ρ=0.062). In this dataset, we will explore the relationship between WMHv and other tissue-based metrics of collateral flow, including the hypoperfusion intensity ratio (HIR) and the cerebral blood volume ratio (rCBV). Conclusions: Our study confirms that patients with CSVD have worse outcomes after AIS. The data also raise the possibility that these worse outcomes in CSVD patients may be mediated by compromised collateral flow in the setting of acute ischemia.

scholarly journals MODERN TRENDS OF BASIC RESEARCH IN PATHOGENESIS OF PROGRESSIVE MYOPIA

2015 ◽  
Vol 69 (3-4) ◽  
pp. 44-49
Author(s):  
E. N. Iomdina ◽  
E. P. Tarutta
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Basic Research ◽  
Individual Treatment ◽  
Myopia Progression ◽  
Neural Processes ◽  
Treatment Plans ◽  
Progressive Myopia ◽  
New Treatment ◽  
And Control

The growing prevalence of progressive myopia and its disabling consequences explains the elaboration of reliable diagnostic markers and new treatment strategies based on the research results of molecular mechanisms underlying the development of the condition. The paper reviews recent basic pathogenetic research studies which have greatly broadened the awareness of the deep causes of progressive myopia associated with the activity of certain growth factors, local and systemic protein metabolism, and regulation of hormonal and neural processes. Practical clinical guidelines for new criteria of diagnosis and control of myopia are published as they could be useful while selecting individual treatment plans including indications to sclera-strengthening therapy and its evaluation. The results may be promising in the elaboration of systemic and local medications for the prevention of myopia progression, which should address the regulation of connective tissue disorders, hormonal shifts, and imbalanced autonomic nervous system. 

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.

scholarly journals The Penumbra system for mechanical thrombectomy in endovascular acute ischemic stroke therapy

Neurology ◽  
2012 ◽  
Vol 79 (Issue 13, Supplement 1) ◽  
pp. S135-S141 ◽  
Author(s):  
S. I. Hussain ◽  
O. O. Zaidat ◽  
B.-F. M. Fitzsimmons
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Stroke Therapy

scholarly journals Merci mechanical thrombectomy retriever for acute ischemic stroke therapy: Literature review

Neurology ◽  
2012 ◽  
Vol 79 (Issue 13, Supplement 1) ◽  
pp. S126-S134 ◽  
Author(s):  
A. Alshekhlee ◽  
D. J. Pandya ◽  
J. English ◽  
O. O. Zaidat ◽  
N. Mueller ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Literature Review ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Stroke Therapy

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 Histological stroke clot analysis after thrombectomy: Technical aspects and recommendations

2019 ◽  
Vol 15 (5) ◽  
pp. 467-476 ◽  
Author(s):  
S Staessens ◽  
S Fitzgerald ◽  
T Andersson ◽  
F Clarençon ◽  
F Denorme ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Procedures ◽  
Cerebral Arteries ◽  
Research Field ◽  
Stroke Therapy ◽  
Technical Aspects ◽  
Stroke Research

The recent advent of endovascular procedures has created the unique opportunity to collect and analyze thrombi removed from cerebral arteries, instigating a novel subfield in stroke research. Insights into thrombus characteristics and composition could play an important role in ongoing efforts to improve acute ischemic stroke therapy. An increasing number of centers are collecting stroke thrombi. This paper aims at providing guiding information on thrombus handling, procedures, and analysis in order to facilitate and standardize this emerging research field.

Recent advances in network medicine: From disease mechanisms to new treatment strategies

2020 ◽  
Vol 26 (5) ◽  
pp. 609-615
Author(s):  
Ítalo Faria do Valle
Keyword(s):  
Molecular Mechanisms ◽  
Biological Significance ◽  
Treatment Strategies ◽  
Molecular Networks ◽  
Network Medicine ◽  
Disease Mechanisms ◽  
Protein Interactome ◽  
Cellular Context ◽  
Human Proteins ◽  
New Treatment

Conventional reductionist approaches have guided most of our understanding in disease diagnostic and treatment. However, most diseases are not consequence of perturbations in a single protein or metabolite, but rather of the effect that these perturbations have in their cellular context. The emerging field of network medicine offers a set of tools to explore molecular networks and to retrieve insights about mechanisms of different diseases. The study of the protein interactome, the map of physical interactions among human proteins, revealed that disease proteins tend to interact with each other, linking diseases to well-defined interactome neighborhoods. These disease-associated neighborhoods have been defined as disease modules, and they can uncover the biological significance of genes identified by genetic studies, reveal molecular mechanisms that connect different phenotypes, and help identify new pharmacological strategies for disease treatment. Therefore, network medicine offers a framework in which the complexity of different aspects of multiple sclerosis can be explored in an integrative fashion, which can ultimately provide insights about disease mechanisms and treatment.

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