Dl-3-n-Butylphthalide (NBP): A Promising Therapeutic Agent for Ischemic Stroke

2018 ◽  
Vol 17 (5) ◽  
pp. 338-347 ◽  
Author(s):  
Shan Wang ◽  
Fei Ma ◽  
Longjian Huang ◽  
Yong Zhang ◽  
Yuchen Peng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Complex Disease ◽  
Time Window ◽  
Recombinant Tissue Plasminogen Activator ◽  
Research Progress ◽  
Apium Graveolens ◽  
Synthetic Compound ◽  
Stroke Treatment ◽  
Single Target ◽  
Anti Oxidant

Background and Objective: Stroke is a leading cause of morbidity and mortality in both developed and developing countries all over the world. The only drug for ischemic stroke approved by FDA is recombinant tissue plasminogen activator (rtPA). However, only 2-5% stroke patients receive rtPAs treatment due to its strict therapeutic time window. As ischemic stroke is a complex disease involving multiple mechanisms, medications with multi-targets may be more powerful compared with single-target drugs. Dl-3-n-Butylphthalide (NBP) is a synthetic compound based on l-3-n- Butylphthalide that is isolated from seeds of Apium graveolens. The racemic 3-n-butylphthalide (dl- NBP) was approved by Food and Drug Administration of China for the treatment of ischemic stroke in 2002. A number of clinical studies indicated that NBP not only improved the symptoms of ischemic stroke, but also contributed to the long-term recovery. The potential mechanisms of NBP for ischemic stroke treatment may target different pathophysiological processes, including anti-oxidant, antiinflammation, anti-apoptosis, anti-thrombosis, and protection of mitochondria et al. Conclusion: In this review, we have summarized the research progress of NBP for the treatment of ischemic stroke during the past two decades.

Current Perspectives Regarding Stem Cell-based Therapy for Ischemic Stroke

2018 ◽  
Vol 24 (28) ◽  
pp. 3332-3340 ◽  
Author(s):  
Kyeong-Ah Kwak ◽  
Ho-Beom Kwon ◽  
Joo Won Lee ◽  
Young-Seok Park
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Time Window ◽  
Experimental Studies ◽  
Cell Type ◽  
Stroke Treatment ◽  
Cell Based Therapy ◽  
Regenerative Approach ◽  
Therapeutic Time Window

Stroke is a leading cause of death and disability worldwide. Conventional treatment has a limitation of very narrow therapeutic time window and its devastating nature necessitate a novel regenerative approach. Transplanted stem cells resulted in functional recovery through multiple mechanisms including neuroprotection, neurogenesis, angiogenesis, immunomodulation, and anti-inflammatory effects. Despite the promising features shown in experimental studies, results from clinical trials are inconclusive from the perspective of efficacy. The present review presents a synopsis of stem cell research on ischemic stroke treatment according to cell type. Clinical trials to the present are briefly summarized. Finally, the hurdles and issues to be solved are discussed for clinical application.

Abstract 215: Differing Perspectives Between Physicians, Patients And Caregivers On The Value Of An Individualized Estimate Of The Benefits Of Thrombolysis At The Time Of Acute Ischemic Stroke: Designing The Resolve (Rapid Evaluation for Stroke Outcomes using Lytics in Vascular Event) Decision Aid

2013 ◽  
Vol 6 (suppl_1) ◽  
Author(s):  
Carole J Decker ◽  
Emily Chhatriwalla ◽  
Brian Garavalia ◽  
John A Spertus ◽  
Er Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Qualitative Interviews ◽  
Treatment Decision ◽  
Recombinant Tissue Plasminogen Activator ◽  
Active Role ◽  
Cultural Barriers ◽  
Emergency Physicians ◽  
Stroke Treatment ◽  
Risks And Benefits

Background: Explaining the risks and benefits of recombinant tissue plasminogen activator (rt-PA) occurs in a hurried conversation in the emergency department and may not be fully grasped by patients and their caregivers. Risk models describing the heterogeneity of benefits from rt-PA in acute ischemic stroke (AIS) have been created, but are not used in routine clinical practice. To develop a tool (RESOLVE) for modeling each patient’s benefits and risks for rt-PA, we conducted qualitative interviews with survivors, their caregivers and emergency physicians to inform the design and improve usability. Methods: A multidisciplinary research team conducted qualitative research through 10 focus groups of survivors and caregivers. We obtained feedback on their preferred role, desired information and their impressions of alternative formats for presenting risk and benefits. Three emergency physicians from 2 sites have been interviewed (with >15 additional physician interviews being currently conducted, the results of which will supplement these preliminary data at the time of presentation). Results: Survivors and caregivers (63 participants: 39 stroke survivors; 43% male) express a need for more information, including specific risks and benefits to treatment. In general, both groups desired an active role in the acute stroke treatment decision. In contrast, the initial physician interviews indicated a hesitancy to provide NINDS data to patients and caregivers, skepticism of the existing data and cultural barriers to the use of rt-PA in AIS, the latter acquired through residency training or the opinions of their clinical colleagues. The interviewed clinicians, however, felt more positive about using rt-PA when a neurologist was readily available to support the decision. Conclusions: Preliminary findings suggest reluctance by emergency physicians to share data about the benefits of rt-PA to stroke patients and their caregivers, despite the desire of the latter for such information. While the additional planned interviews will be needed to confirm these findings, preliminary insights suggest a compelling need to overcome the reticence of emergency physicians to use clinical data to better engage patients in making a shared decision about rt-PA in AIS.

Abstract TP52: Endovascular Therapy in Patients Over 80 Years of Age With Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Janhavi M Modak ◽  
Syed Daniyal Asad ◽  
Jussie Lima ◽  
Amre Nouh ◽  
Ilene Staff ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Symptom Onset ◽  
Time Window ◽  
Extended Time ◽  
Stroke Patients ◽  
Stroke Outcomes ◽  
Stroke Treatment ◽  
Group A ◽  
Group B

Introduction: Acute ischemic stroke treatment has undergone a paradigm shift, with patients being treated in the extended time window (6-24 hours post symptom onset). The purpose of this study is to assess outcomes in stroke patients above 80 years of age undergoing endovascular treatment (EVT) in the extended time window. Methods: Acute ischemic stroke patients presenting to Hartford Hospital between January 2017 to June 2019 were considered for the study. Stroke outcomes in patients above 80 years of age with anterior circulation ischemic strokes presenting in the extended time window (Group A, n=30) were compared to a younger cohort of patients below 80 years (Group B, n=31). Patients over 80 years treated in the traditional time window (within 6 hours of symptom onset) served as a second set of controls (Group C, n=40). Statistical analysis was performed with a significance level of 0.05 Results: For angiographic results, there were no statistically significant differences in terms of good outcomes (TICI 2b-3) among patients of Group A, when compared to Groups B or C (p>0.05). For the endovascular procedures, no significant differences were noted in the total fluoroscopy time (Median Group A 44.05, Group B 38.1, Group C 35.25 min), total intra-procedure time (Median Group A 144, Group B 143, Group C 126 min) or total radiation exposure (Median Group A 8308, Group B 8960, Group C 8318 uGy-m 2 ). For stroke outcomes, a good clinical outcome was defined as modified Rankin score of 0-2 at discharge. Significantly better outcomes were noted in the younger patients in Group B - 35.4%, when compared to 13.3% in Group A (p=0.03). Comparative outcomes differed in the elderly patients above 80 years, Group A -13.3% vs Group C - 25%, although not statistically significant (p=0.23). There was a significant difference in mortality in patients of Group A - 40% as compared to 12% in the younger cohort, Group B (p= 0.01). Conclusions: In the extended time window, patients above 80 years of age were noted to have a higher mortality, morbidity compared to the younger cohort of patients. No significant differences were noted in the stroke outcomes in patients above 80 years of age when comparing the traditional and the extended time window for stroke treatment.

scholarly journals Lessons from Recent Advances in Ischemic Stroke Management and Targeting Kv2.1 for Neuroprotection

2020 ◽  
Vol 21 (17) ◽  
pp. 6107 ◽  
Author(s):  
Chung-Yang Yeh ◽  
Anthony J. Schulien ◽  
Bradley J. Molyneaux ◽  
Elias Aizenman
Keyword(s):  
Ischemic Stroke ◽  
Time Window ◽  
Stroke Therapy ◽  
Stroke Management ◽  
Preclinical Research ◽  
Endovascular Thrombectomy ◽  
Stroke Treatment ◽  
Cell Death Pathway ◽  
To Receive ◽  
Neuroprotective Therapies

Achieving neuroprotection in ischemic stroke patients has been a multidecade medical challenge. Numerous clinical trials were discontinued in futility and many were terminated in response to deleterious treatment effects. Recently, however, several positive reports have generated the much-needed excitement surrounding stroke therapy. In this review, we describe the clinical studies that significantly expanded the time window of eligibility for patients to receive mechanical endovascular thrombectomy. We further summarize the results available thus far for nerinetide, a promising neuroprotective agent for stroke treatment. Lastly, we reflect upon aspects of these impactful trials in our own studies targeting the Kv2.1-mediated cell death pathway in neurons for neuroprotection. We argue that recent changes in the clinical landscape should be adapted by preclinical research in order to continue progressing toward the development of efficacious neuroprotective therapies for ischemic stroke.

scholarly journals Reflection on the Past, Present, and Future of Thrombolytic Therapy for Acute Ischemic Stroke

Neurology ◽  
2021 ◽  
Vol 97 (20 Supplement 2) ◽  
pp. S170-S177
Author(s):  
Stacie L. Demel ◽  
Robert Stanton ◽  
Yasmin N. Aziz ◽  
Opeolu Adeoye ◽  
Pooja Khatri
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Ct Perfusion ◽  
Critical Role ◽  
Recombinant Tissue Plasminogen Activator ◽  
Initial Time ◽  
Stroke Treatment ◽  
The Past ◽  
Therapeutic Landscape

More than 25 years have passed since the US Food and Drug Administration approved IV recombinant tissue plasminogen activator (alteplase) for the treatment of acute ischemic stroke. This landmark decision brought a previously untreatable disease into a new therapeutic landscape, providing inspiration for clinicians and hope to patients. Since that time, the use of alteplase in the clinical setting has become standard of care, continually improving with quality measures such as door-to-needle times and other metrics of specialized stroke unit care. The past decade has seen more widespread use of alteplase in the prehospital setting with mobile stroke units and telestroke and beyond initial time windows via the use of CT perfusion or MRI. Simultaneously, the position of alteplase is being challenged by new lytics and by the concept of its bypass altogether in the era of endovascular therapy. We provide an overview of alteplase, including its earliest trials and how they have shaped the current therapeutic landscape of ischemic stroke treatment, and touch on new frontiers for thrombolytic therapy. We highlight the critical role of thrombolytic therapy in the past, present, and future of ischemic stroke care.

Abstract P875: Disparities in Delivery of Endovascular Therapy: Data From the Florida State Registry

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Nastajjia Krementz ◽  
Kefeng Wang ◽  
Carolina M Gutierrez ◽  
Antonio Bustillo ◽  
Nils H Mueller ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Therapy ◽  
Treatment Time ◽  
Time Window ◽  
Systems Of Care ◽  
Multivariable Analysis ◽  
South Florida ◽  
Stroke Patients ◽  
Stroke Treatment ◽  
High Volume Hospital

Background: Access to endovascular therapy (EVT) should be equitable to all eligible ischemic stroke patients presenting within the treatment time window. In the Florida Stroke Registry (FSR) we sought to determine sex, race/ethnic, hospital and regional disparities in the delivery of EVT. Methods: From January 2010 to January 2020, a total of 99,088 ischemic stroke cases within 24 hours of symptom onset were enrolled. Multivariable logistic regression with generalized estimating equations evaluated independent predictors of EVT utilization. Results: A total of 7,812 patients received EVT (51.2% female, mean age 71.3 ± SD 14.6 years, 61.4% white, 17.4% black, 21.2% Hispanic). Compared to those not treated, EVT treated patients were more likely Hispanic (21.2% vs. 14.6%), arrived earlier to the hospital (median 120 min (IQR 292) vs. 170 min (IQR 446)), via EMS (94% vs. 66%), with more severe strokes (median NIHSS 15 (IQR11) vs. 5 (IQR 9)), to large hospitals (≥ 680 beds) (73.4% vs. 47.7%), in South Florida (50.8% vs. 38.2%). In multivariable analysis, female sex (OR 1.05, 95% CI 1-1.11), atrial fibrillation (OR 1.57, 95% CI 1.45-1.7), higher NIHSS (> 6) (OR 6.19, 95% CI 5.11-7.51) and presenting to a high-volume hospital (OR 3.47, 95% CI 2.25-5.36) positively predicted EVT utilization, whereas older age (>80 years) (OR 0.88, 95% CI 0.80-0.96), and black race (vs. white OR 0.87, 95% CI 0.76-1), were independently associated with lower use of EVT. Conclusions: In this large state-wide registry study, we found significant race-ethic and geographical disparities in delivery of EVT. Systems of care should address disparities in stroke treatment to improve access to EVT for all eligible stroke patients.

scholarly journals Strategies to Extend Thrombolytic Time Window for Ischemic Stroke Treatment: An Unmet Clinical Need

2017 ◽  
Vol 19 (1) ◽  
pp. 50-60 ◽  
Author(s):  
Ike dela Peña ◽  
Cesar Borlongan ◽  
Guofang Shen ◽  
Willie Davis
Keyword(s):  
Ischemic Stroke ◽  
Time Window ◽  
Stroke Treatment

scholarly journals Methodology for the Canadian Activase for Stroke Effectiveness Study (CASES)

2001 ◽  
Vol 28 (3) ◽  
pp. 232-238 ◽  
Author(s):  
Michael D. Hill ◽  
Alastair M. Buchan ◽  
The CASES Investigators
Keyword(s):  
Ischemic Stroke ◽  
Recombinant Tissue Plasminogen Activator ◽  
Effectiveness Study ◽  
Multiple Stakeholders ◽  
Stakeholder Collaboration ◽  
Stroke Treatment ◽  
Early Results ◽  
Canadian Context ◽  
Tissue Plasminogen ◽  
Multi Stakeholder

Background:Intravenous recombinant tissue plasminogen activator (tPA, alteplase) was conditionally licensed for the treatment of acute ischemic stroke (AIS) in Canada on February 17, 1999. As a condition of licensure, the Canadian Activase for Stroke Effectiveness Study (CASES) was established to monitor the use of alteplase for AIS in Canada. The study involves multiple stakeholders.Methods:CASES is a prospective registry of patients treated with alteplase for AIS. The purposes of this registry are to ensure the safety of the drug in the Canadian context, to assess effectiveness of alteplase for AIS and to gather further information to try to establish which patients are most likely to benefit from treatment.Results:Both community (n=25) and tertiary centres (n=35) have enrolled a total of 944 patients to date. Early results suggest that thrombolytic stroke treatment is both safe and effective among these centres.Conclusion:This paper outlines the development of and methods for the CASES study. The study is an example of a multi-stakeholder collaboration to advance the care of patients with acute stroke.

Tenecteplase for Acute Ischemic Stroke Treatment

2021 ◽  
Vol 41 (01) ◽  
pp. 028-038
Author(s):  
Alison E. Baird ◽  
Richard Jackson ◽  
Weijun Jin
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Recombinant Tissue Plasminogen Activator ◽  
The United States ◽  
Similar Efficacy ◽  
Plasminogen Activator Inhibitor 1 ◽  
Stroke Treatment ◽  
United States Food

AbstractThe introduction of thrombolytic therapy in the 1990s has transformed acute ischemic stroke treatment. Thus far, intravenous recombinant tissue plasminogen activator (rt-PA) also known as alteplase is the only thrombolytic proven to be efficacious and approved by the United States Food and Drug Administration. But the thrombolytic agent tenecteplase (TNK) is emerging as a potential replacement for rt-PA. TNK has greater fibrin specificity, slower clearance, and higher resistance to plasminogen activator inhibitor-1 than rt-PA. Hence, TNK has the potential to provide superior lysis with fewer hemorrhagic complications. Also, easier bolus-only administration makes TNK a very practical rt-PA alternative. In several clinical trials, TNK has shown similar efficacy and safety to rt-PA, and the potential to be at least noninferior to rt-PA in some settings. TNK may be superior to rt-PA for reperfusing large vessel occlusions in patients with salvageable penumbra, although this has not yet translated to improved clinical outcomes. Further phase 3 studies are in progress comparing rt-PA with TNK for acute ischemic stroke during the first 4.5 hours. Studies are also in progress to evaluate the use of TNK for extended applications, such as wake-up stroke.

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