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Thrombolytic, stroke, extend window

Min Li, Jing Zhou, Weifeng Jin, Xiaohong Li, Yuyan Zhang
Background: Hemorrhagic transformation, neurotoxicity, short treatment time windows, and other defects are considered as the major limitations for the thrombolytic therapy. This study is devoted to figure out whether Danhong injection (DHI) combined with tissue-plasminogen activator (t-PA) could extend the treatment time windows and ameliorate brain injury, hemorrhagic complication and BBB disruption after focal embolic stroke. Methods: In vitro , the combined concentrations of DHI and t-PA were added to wells reacted with plasminogen and D-Val-Leu-Lys-AMC...
2018: Frontiers in Pharmacology
Shan Liu, Xiaozhou Feng, Rong Jin, Guohong Li
Thrombolysis with intravenous tissue plasminogen activator (tPA) is the only FDA approved treatment for patients with acute ischemic stroke, but its use is limited by narrow therapeutic window, selective efficacy, and hemorrhagic complication. In the past two decades, extensive efforts have been undertaken to extend its therapeutic time window and explore alternative thrombolytic agents, but both show little progress. Nanotechnology has emerged as a promising strategy to improve the efficacy and safety of tPA...
February 2018: Expert Opinion on Drug Delivery
Masumeh Zamanlu, Mehdi Farhoudi, Morteza Eskandani, Javad Mahmoudi, Jaleh Barar, Mohammad Rafi, Yadollah Omidi
Tissue plasminogen activator (tPA) is the only FDA approved medical treatment for the ischaemic stroke. However, it associates with some inevitable limitations, including: short therapeutic window, extremely short half-life and low penetration in large clots. Systemic administration may lead to complications such as haemorrhagic conversion in the brain and relapse in the form of re-occlusion. Furthermore, ultrasound has been utilised in combination with contrast agents, echogenic liposome, microspheres or nanoparticles (NPs) carrying tPA for improving thrombolysis - an approach that has resulted in slight improvement of tPA delivery and facilitated thrombolysis...
February 2018: Journal of Drug Targeting
Mohammadreza Zarisfi, Fatemeh Allahtavakoli, Mahsa Hassanipour, Mohammad Khaksari, Hossain Rezazadeh, Mohammad Allahtavakoli, Mohammad Mohsen Taghavi
It has been reported that restriction of reperfusion after thrombolytic therapy in ischemic stroke may reduce tissue plasminogen activator (tPA) adverse effects and extend its time window. We examined whether shortIt has been reported that restriction of reperfusion after thrombolytic therapy in ischemic stroke may reduce tissue plasminogen activator (tPA) adverse effects and extend its time window. We examined whether short-term and mild local brain cooling can prevent hyperemia and/or adverse effects of delayed tPA in rat embolic stroke model...
July 11, 2017: Brain Research Bulletin
Wen-Cao Liu, Xin-Chun Jin
The presence of a salvageable penumbra, a region of ischemic brain tissue with sufficient energy for short-term survival, has been widely agreed as the premise for thrombolytic therapy with tissue plasminogen activator (tPA), which remains the only United States Food and Drug Administration (FDA) approved treatment for acute ischemia stroke. However, the use of tPA has been profoundly constrained due to its narrow therapeutic time window and the increased risk of potentially deadly hemorrhagic transformation (HT)...
October 2016: Medical Gas Research
Ike Dela Peña, Cesar Borlongan, Guofang Shen, Willie Davis
To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment...
January 2017: Journal of Stroke
Zhe Shen, Yanrong Zheng, Jiaying Wu, Ying Chen, Xiaoli Wu, Yiting Zhou, Yang Yuan, Shousheng Lu, Lei Jiang, Zhenghong Qin, Zhong Chen, Weiwei Hu, Xiangnan Zhang
Prompt reperfusion after cerebral ischemia is critical for neuronal survival. Any strategies that extend the limited reperfusion window will be of great importance. Acidic postconditioning (APC) is a mild acidosis treatment that involves inhaling CO2 during reperfusion following ischemia. APC attenuates ischemic brain injury although the underlying mechanisms have not been elucidated. Here we report that APC reinforces ischemia-reperfusion-induced mitophagy in middle cortical artery occlusion (MCAO)-treated mice, and in oxygen-glucose deprivation (OGD)-treated brain slices and neurons...
March 4, 2017: Autophagy
Ahmet Yigit Goktay, Cagin Senturk
Deep venous thrombosis (DVT) is a common disorder with a significant mortality rate. Successful endovascular treatment of acute DVT is most likely to be achieved in patients with recently formed thrombus, (<10-14 days) with acute iliofemoral DVT. Endovascular treatment options include: Catheter-directed thrombolysis (CDT), pharmacomechanical catheter-directed thrombolysis (PCDT), percutaneous aspiration thrombectomy (PAT), vena cava filter protection, venous balloon dilatation and venous stent implantation...
2017: Advances in Experimental Medicine and Biology
Han-Sen Chen, Su-Hua Qi, Jian-Gang Shen
Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA&#039;s therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multitarget strategy is warranted to resolve such complex disease...
2017: Current Neuropharmacology
Tobias A Mattei, Azeem A Rehman, Carlos R Goulart, Marília G Sória, Vanessa Rizelio, Murilo S Meneses
BACKGROUND: Although intravenous thrombolysis is the Food and Drug Administration-approved treatment for acute ischemic stroke (AIS) within 3 h, combined intravenous and intra-arterial thrombolysis with endovascular techniques may be able to extend this traditional time window. CASE DESCRIPTION: We present the clinical evolution of a 45-year-old male presenting with acute left hemiparesis. Magnetic resonance imaging revealed a small diffusion restriction at the right basal ganglia with perfusion compromise in the entire right middle cerebral artery (MCA) territory...
2016: Surgical Neurology International
Han-Sen Chen, Su-Hua Qi, Jian-Gang Shen
Tissue plasminogen activator (t-PA) is the only FDA approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seems not satisfying, and a multi-target strategy is warranted to resolve such complex disease...
December 7, 2015: Current Neuropharmacology
Teruyuki Hirano
Currently, the indication for thrombolytic therapy using intravenous recombinant tissue plasminogen activator (rt-PA) is restricted strictly to patients with acute ischemic stroke within 4.5 h of onset. The effect of rt-PA declines over time; therefore, we need to minimize the time delay while generating imaging information. The use of cerebral blood flow imaging is not recommended within this time window. Conversely, the balance of efficacy and the risk of bleeding complications differ among patients > 4...
2015: Neurologia Medico-chirurgica
Zhenjun Tan, Brandon P Lucke-Wold, Aric F Logsdon, Ryan C Turner, Cong Tan, Xinlan Li, Jarin Hongpaison, Daniel L Alkon, James W Simpkins, Charles L Rosen, Jason D Huber
Blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT) following ischemic/reperfusion injury contributes to post-stroke morbidity and mortality. Bryostatin, a potent protein kinase C (PKC) modulator, has shown promise in treating neurological injury. In the present study, we tested the hypothesis that administration of bryostatin would reduce BBB disruption and HT following acute ischemic stroke; thus, prolonging the time window for administering recombinant tissue plasminogen activator (r-tPA)...
October 5, 2015: European Journal of Pharmacology
Randolph S Marshall
IMPORTANCE: Intravenous recombinant tissue plasminogen activator (alteplase) was approved by the US Food and Drug Administration in 1996 for the treatment of acute ischemic stroke. Nearly 20 years later, it remains the only approved treatment, despite limitations in both efficacy and safety. With a growing capacity for stroke treatment worldwide, physicians need to understand where we have come from and what the future of stroke treatment might be. OBJECTIVE: To present a historical prospective as well as current trends in thrombolytic therapy, focusing on characteristics of drugs that have worked and clinical trials that are moving the field forward...
August 2015: JAMA Neurology
Zhenjun Tan, Xinlan Li, Ryan C Turner, Aric F Logsdon, Brandon Lucke-Wold, Kenneth DiPasquale, Soon Soeg Jeong, Ridong Chen, Jason D Huber, Charles L Rosen
Recombinant tissue plasminogen activator (r-tPA) is the only FDA-approved drug treatment for ischemic stroke and must be used within 4.5h. Thrombolytic treatment with r-tPA has deleterious effects on the neurovascular unit that substantially increases the risk of intracerebral hemorrhage if administered too late. These therapeutic shortcomings necessitate additional investigation into agents that can extend the therapeutic window for safe use of thrombolytics. In this study, combination of r-tPA and APT102, a novel form of human apyrase/ADPase, was investigated in a clinically-relevant aged-female rat embolic ischemic stroke model...
September 5, 2014: European Journal of Pharmacology
Marie Dagonnier, David W Howells, Geoffrey A Donnan, Helen M Dewey
To increase the percentage of acute stroke patients benefiting from thrombolysis, the utility of expanding the time window of treatment beyond 4.5 hours after stroke onset needs to be investigated. We aimed to identify the target population and the challenges of recruitment of patients for the time window beyond 4.5 hours. Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND), a multicentre randomised controlled trial testing the efficacy of thrombolytic therapy in patients with clinically significant ischaemic penumbra between 4...
July 2014: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Andrew Bivard, Longting Lin, Mark W Parsonsb
The cornerstone of acute ischemic stroke treatment relies on rapid clearance of an offending thrombus in the cerebrovascular system. There are various drugs and different methods of assessment to select patients more likely to respond to treatment. Current clinical guidelines recommend the administration of intravenous alteplase (following a brain noncontract CT to exclude hemorrhage) within 4.5 hours of stroke onset. Because of the short therapeutic time window, the risk of hemorrhage, and relatively limited efficacy of alteplase for large clot burden, research is ongoing to find more effective and safer reperfusion therapy, as well as focussing on refinement of patient selection for acute reperfusion treatment...
May 2013: Journal of Stroke
Weihua Guan, Yumei Zhao, Chao Xu
Combination treatment may target different pathophysiological events following cerebral ischemia thus enhancing the efficacy of treatment in thromboembolic stroke. Taurine confers a neuroprotective effect in the mechanical stroke model. This effect has not been assessed in an embolic stroke model. Here, we sought to evaluate the neuroprotective effect of taurine alone and in combination with thrombolytic therapy to investigate whether combined administration would extend the therapeutic time window without increasing the hemorrhagic transformation in a rat embolic stroke model...
March 2011: Translational Stroke Research
Adriana Sofia Ploneda Perilla, Michael J Schneck
This article reviews some of the current literature in support or against extension of the intravenous tissue plasminogen activator window, use of intra-arterial therapy or devices, as well alternative pharmacologic therapies that may extend the window for treatment of patients with acute ischemic stroke, with consideration of the relative risk of thrombolytic complications, factors for worse outcomes, and unclear stroke onset, as seen in patients with wake-up stroke. The issue of newer concomitant antithrombotic therapies as they affect the decision for acute ischemic stroke thrombolytic therapy is also explored...
August 2013: Neurologic Clinics
Muhammad Faisal Wadiwala, Ayeesha Kamran Kamal
No abstract text is available yet for this article.
August 2012: JPMA. the Journal of the Pakistan Medical Association
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