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Rt-pa bbb

Junfei Gu, Juan Chen, Nan Yang, Xuefeng Hou, Jing Wang, Xiaobin Tan, Liang Feng, Xiaobin Jia
ETHNOPHARMACOLOGICAL RELEVANCE: Combination of Ligusticum chuanxiong and Radix Paeoniae (XS) is highly effective in the treatment for focal cerebral ischemic, but the underlying mechanism is not clear. This study was conducted to evaluate the combinative effects of XS on MCAO rats and explore the underlying mechanisms. MATERIALS AND METHODS: MCAO rats were used to evaluate the protective effect of Ligusticum chuanxiong (CX), Radix Paeoniae Rubra (CS) and their combination (XS) on ameliorating focal cerebral ischemic...
July 1, 2016: Journal of Ethnopharmacology
Yi-Ping You
BACKGROUND: Ischemic stroke is the leading cause of death and disability worldwide. To date, recombinant tissue plasminogen activator (rt-PA) remains the only safe and effective pharmaceutical treatment for brain ischemia, but delayed rt-PA administration leads to hyperperfusion, which severely limits its clinical efficacy. METHODS: In this study, we investigated the effect of epigallocatechin gallate (EGCG) in extending the therapeutic window of rt-PA using a rat middle cerebral artery occlusion (MCAO) model...
April 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Yasuhiro Suzuki, Nobuo Nagai, Kazuo Umemura
Cerebrovascular homeostasis is maintained by the blood-brain barrier (BBB), which forms a mechanical and functional barrier between systemic circulation and the central nervous system (CNS). In patients with ischemic stroke, the recombinant tissue-type plasminogen activator (rt-PA) is used to accelerate recanalization of the occluded vessels. However, rt-PA is associated with a risk of increasing intracranial bleeding (ICB). This effect is thought to be caused by the increase in cerebrovascular permeability though various factors such as ischemic reperfusion injury and the activation of matrix metalloproteinases (MMPs), but the detailed mechanisms are unknown...
2016: Frontiers in Cellular Neuroscience
Yuh-Chiang Shen, Chung-Kuang Lu, Kuo-Tong Liou, Yu-Chang Hou, Yun-Lan Lin, Yea-Hwey Wang, Hsing-Jen Sun, Ko-Hsun Liao, Hsei-Wei Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Four traditional Chinese herbal remedies (CHR) including Buyang Huanwu decoction (BHD), Xuefu Zhuyu decoction (XZD), Tianma Gouteng decoction (TGD) and Shengyu decoction (SYD) are popular used in treating brain-related dysfunction clinically with different syndrome/pattern based on traditional Chinese medicine (TCM) principles, yet their neuroprotective mechanisms are still unclear. MATERIALS AND METHODS: Mice were subjected to an acute ischemic stroke to examine the efficacy and molecular mechanisms of action underlying these CHR...
September 15, 2015: Journal of Ethnopharmacology
Yasuhiro Suzuki, Nobuo Nagai, Kasumi Yamakawa, Yoshinori Muranaka, Kazuya Hokamura, Kazuo Umemura
Recombinant tissue-type plasminogen activator (rt-PA) modulates cerebrovascular permeability and exacerbates brain injury in ischemic stroke, but its mechanisms remain unclear. We studied the involvement of vascular endothelial growth factor (VEGF)-mediated endocytosis in the increase of blood-brain barrier (BBB) permeability potentiated by rt-PA after ischemic stroke. The rt-PA treatment at 4 hours after middle cerebral artery occlusion induced a transient increase in BBB permeability after ischemic stroke in mice, which was suppressed by antagonists of either low-density lipoprotein receptor families (LDLRs) or VEGF receptor-2 (VEGFR-2)...
December 2015: Journal of Cerebral Blood Flow and Metabolism
Yingyuan Cai, Xinfeng Liu, Weixian Chen, Zhenzhen Wang, Gelin Xu, Yanying Zeng, Yuping Ma
Transforming growth factor-beta1 (TGF-β1) is well known to promote extracellular matrix accumulation. Recent studies demonstrated that TGF-β1 protects against blood-brain barrier (BBB) disruption in the condition of inflammatory pain and stroke. In the present study, we investigated whether TGF-β1 can maintain BBB integrity and prevent hemorrhagic transformation (HT) after recombinant tissue plasminogen activator (rt-PA) treatment in a rat model of thromboembolic middle cerebral artery occlusion (MCAO). Three hours after MCAO, rats were given saline, rt-PA alone or rt-PA combined with TGF-β1 intravenously...
April 2015: Experimental Neurology
Xinping Ren, Yong Wang, Yi Wang, Hong Chen, Li Chen, Yi Liu, Chengshi Xu
OBJECTIVE: To evaluate effect of thrombolytic therapy with rt-PA (recombinant tissue plasminogen activator) and transcranial color Doppler ultrasound (TCCS) combined with microbubbles on histology of brain tissue. METHODS: New Zealand rabbits were subjected to TCCS based thrombolytic therapy, in 8 groups depending on dose of rt-PA, exposure duration of TCCS and presence of attenuation by skull bone window, 2 animals/group: (1) skull+1/2 rt-PA+TCCS+MBs, 10 min, (2) skull+rt-PA+TCCS+MBs, 10 min, (3) skull+1/2 rt-PA+TCCS+MBs, 20 min, (4) skull+rt-PA+TCCS+MBs, 20 min, (5) skull+1/2 rt-PA+TCCS+MBs, 30 min, (6) skull+rt-PA+TCCS+MBs, 30 min, (7) 1/2 rt-PA+TCCS+MBs, 10 min, (8) 1/2 rt-PA+TCCS+MBs, 20 min...
April 2015: Clinical Neurology and Neurosurgery
Jun Cai, Ruihuan Pan, Xiang Jia, Yue Li, Zijun Hou, Run-Yue Huang, Xin Chen, Shengping Huang, Guo-Yuan Yang, Jingbo Sun, Yan Huang
ETHNOPHARMACOLOGICAL RELEVANCE: Haemorrhagic transformation is an asymptomatic event that frequently occurs after following ischaemic stroke, particularly when pharmaceutical thrombolysis is used. However, the mechanism responsible for haemorrhagic transformation remains unknown, and therapeutics have not been identified. In this study, we administered a combination of astragalus membranaceus and ligustrazine to rats with cerebral ischaemia that had undergone thrombolysis. We analysed the effect of this combination on the attenuation of haemorrhagic transformation and the maintenance of blood-brain barrier integrity...
December 2, 2014: Journal of Ethnopharmacology
Brandon J Thompson, Patrick T Ronaldson
Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events in neurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality...
2014: Advances in Pharmacology
Akira Ito, Kuniyasu Niizuma, Hiroaki Shimizu, Miki Fujimura, Keiji Hasumi, Teiji Tominaga
Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a new thrombolytic agent that exhibits anti-inflammatory effects. We previously demonstrated that the hemorrhagic transformation was fewer with SMTP-7 than with recombinant tissue plasminogen activator (rt-PA) following ischemia-reperfusion in animal models. We hypothesized that SMTP-7 may decrease hemorrhagic transformation after ischemia-reperfusion under the warfarin-treated condition. Transient middle cerebral artery occlusion (MCAO) was induced for 3h using an intraluminal suture in warfarin-treated mice to produce hemorrhagic transformation...
August 26, 2014: Brain Research
Shuyan Zheng, Ying-Ying Bai, Yinzhi Changyi, Xihui Gao, Wenqing Zhang, Yuancheng Wang, Lu Zhou, Shenghong Ju, Cong Li
Ischemic stroke accounts for 80% strokes and originates from a reduction of cerebral blood flow (CBF) after vascular occlusion. For treatment, the first action is to restore CBF by thrombolytic agent recombinant tissue-type plasminogen activator (rt-PA). Although rt-PA benefits clinical outcome, its application is limited by short therapeutic time window and risk of brain hemorrhage. Different to thrombolytic agents, neuroprotectants reduce neurological injuries by blocking ischemic cascade events such as excitotoxicity and oxidative stress...
November 2014: Advanced Healthcare Materials
Aijia Cai, Frieder Schlunk, Ferdinand Bohmann, Sepide Kashefiolasl, Robert Brunkhorst, Christian Foerch, Waltraud Pfeilschifter
BACKGROUND: Systemic thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the standard of acute stroke care. Its potential to increase the risk of secondary intracerebral hemorrhage, especially if administered late, has been ascribed to its proteolytic activity that has detrimental effects on blood-brain barrier (BBB) integrity after stroke. FTY720 has been shown to protect endothelial barriers in several disease models such as endotoxin-induced pulmonary edema and therefore is a promising candidate to counteract the deleterious effects of rt-PA...
2013: Experimental & Translational Stroke Medicine
Fei Teng, Virginie Beray-Berthat, Bérard Coqueran, Clémentine Lesbats, Mélanie Kuntz, Bruno Palmier, Marie Garraud, Cyrielle Bedfert, Niamh Slane, Vincent Bérézowski, Frédéric Szeremeta, Johan Hachani, Daniel Scherman, Michel Plotkine, Bich-Thuy Doan, Catherine Marchand-Leroux, Isabelle Margaill
Recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment approved for thrombolysis in patients suffering from ischemic stroke, but its administration aggravates the risk of hemorrhagic transformations. Experimental data demonstrated that rt-PA increases the activity of poly(ADP-ribose)polymerase (PARP). The aim of the present study was to investigate whether PJ34, a potent (PARP) inhibitor, protects the blood-brain barrier components from rt-PA toxicity. In our mouse model of cerebral ischemia, administration of rt-PA (10 mg/kg, i...
October 2013: Experimental Neurology
Xian Nan Tang, Liping Liu, Maya A Koike, Midori A Yenari
Therapeutic hypothermia has shown neuroprotective promise, but whether it can be used to improve outcome in stroke has yet to be determined in patients. Recombinant tissue plasminogen activator (rt-PA) is only given to a minority of patients with acute ischemic stroke, and is not without risk, namely significant brain hemorrhage.We explored whether mild hypothermia, in combination with rt-PA, influences the safety of rt-PA. Mice were subjected to middle cerebral artery occlusion (MCAO) using a filament model, followed by 24 hours reperfusion...
June 2013: Therapeutic Hypothermia and Temperature Management
Li Sun, Wei Zhou, Robert Ploen, Markus Zorn, Roland Veltkamp
Dabigatran etexilate (DE) has recently been introduced for stroke prevention in atrial fibrillation, but management of acute ischaemic stroke during therapy with DE is a challenge. Thrombolysis is contraindicated because of a presumed increased risk of intracerebral haemorrhagic complications. We studied in different ischaemia models whether DE increases secondary haemorrhage after thrombolysis. C57BL/6 mice were anticoagulated with high-dose DE or warfarin. After 2 hour (h) or 3 h transient filament MCAO, rt-PA was injected...
July 2013: Thrombosis and Haemostasis
Marianne Haddad, Virginie Beray-Berthat, Bérard Coqueran, Michel Plotkine, Catherine Marchand-Leroux, Isabelle Margaill
Recombinant tissue-type plasminogen activator (rt-PA) is presently the only pharmacological treatment approved for thrombolysis in patients suffering from ischemic stroke. Although reperfusion of ischemic tissue is essential, the use of rt-PA is limited due to its narrow therapeutic window and risk of hemorrhagic transformations. Recent studies have shown that rt-PA amplifies the post-ischemic activation of the nuclear enzyme poly(ADP-ribose)polymerase (PARP). This enzyme has been shown to contribute to both the breakdown of the blood brain barrier and spontaneous hemorrhagic transformations after ischemia...
August 2013: Fundamental & Clinical Pharmacology
Bernd Kallmünzer, Stefan Schwab, Rainer Kollmar
BACKGROUND: Hypothermia is neuroprotective in experimental stroke and may extend the so far limited therapeutic time window for thrombolysis. Therefore, hypothermia of 34°C and its effects on delayed thrombolysis including reperfusion-associated injury were investigated in a model of thromboembolic stroke (TE). METHODS: Male Wistar rats (n = 48) were subjected to TE. The following treatment groups were investigated: control group - normothermia (37°C); thrombolysis group - rt-PA 90 min after TE; hypothermia by 34°C applied 1...
2012: Experimental & Translational Stroke Medicine
Hai-Tao Lu, Jun-Gong Zhao, Ming-Hua Li, Yong-Dong Li
To explore whether human albumin (Alb) administration prior to thrombolysis with recombinant tissue plasminogen activator (rt-PA) can eliminate brain damage induced by this treatment given after the effective and safe window of 3h after stroke onset. Rats were subjected to embolic stroke by unilateral embolic middle cerebral artery occlusion (MCAO). Three or six hours after the onset of stroke, rats were administered intravenously with saline (control), rt-PA (thrombolysis) or rt-PA+Alb (additional Alb 3h after MCAO, combination)...
February 15, 2012: Brain Research
Li Sun, Wei Zhou, Sabine Heiland, Hugo H Marti, Roland Veltkamp
Secondary hemorrhage after thrombolysis in ischemic stroke is an important complication, which has been difficult to study in preclinical disease models. We have established and characterized a model of thromboembolic middle cerebral artery occlusion in rats. Advantages of this model include a very low rate of spontaneous recanalization and good reperfusion after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). In vivo T2* MR imaging and postmortem assays were used for quantification of secondary brain hemorrhage...
January 12, 2011: Brain Research
Michal Rozanski, Martin Ebinger, Wolf U Schmidt, Benjamin Hotter, Sandra Pittl, Peter U Heuschmann, Jan G Jungehuelsing, Jochen B Fiebach
OBJECTIVES: The hyperintense acute reperfusion marker (HARM) has been described as a predictor for haemorrhagic transformation (HT) in acute ischaemic stroke. We hypothesised that this phenomenon is not present in the elderly. METHODS: It was possible to assess 47/84 consecutive patients aged 80 and over with diagnosed ischaemic stroke or transient ischaemic attack (TIA). MRI was performed within 24 h of onset of symptoms with follow-up MRI within a further 48 h...
December 2010: European Radiology
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