The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform
R. Loch Macdonald - One of the best experts on this subject based on the ideXlab platform.
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Dissociation of Vasospasm and Secondary Effects of Experimental Subarachnoid Hemorrhage by Clazosentan
Stroke, 2011Co-Authors: Mohammed Sabri, R. Loch MacdonaldAbstract:Background and Purpose—Endothelin receptor antagonists such as clazosentan decrease large-artery vasospasm after experimental and clinical subarachnoid hemorrhage. We used clazosentan to gain insight into the pathophysiology of subarachnoid hemorrhage by determining if decreasing vasospasm is associated with alleviation of other secondary complications of subarachnoid hemorrhage such as oxidative stress, endothelial nitric oxide synthase dysfunction, microthromboembolism, and neuronal injury. Methods—Mice were subjected to subarachnoid hemorrhage by injection of blood into the Chiasmatic Cistern. They were treated with clazosentan or vehicle by continuous intraperitoneal infusion for 48 hours. Middle cerebral artery vasospasm, superoxide anion radical, peroxynitrite, microthromboemboli, endothelial nitric oxide synthase uncoupling, cerebral blood flow, neuronal injury, and mortality were assessed. Results—Clazosentan preserved cerebral blood flow, alleviated vasospasm, and decreased mortality but did not ...
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Different effects of clazosentan on consequences of subarachnoid hemorrhage in rats.
Brain Research, 2011Co-Authors: Gang Chen, Mohammed Sabri, Asma Tariq, Hyojin Jeon, Elaine J.y. Tang, Katarina Lakovic, Hoyee Wan, R. Loch MacdonaldAbstract:One of the major complications after subarachnoid hemorrhage (SAH) is angiographic vasospasm in the large arteries at the base of the brain. However, a clinical trial of clazosentan demonstrated a 65% relative risk reduction in angiographic vasospasm but no effect on mortality or clinical outcome, raising questions about the role of angiographic vasospasm played in outcome after SAH. The purpose of this study was to determine if reducing or reversing angiographic vasospasm with clazosentan reduced other secondary complications such as microthromboembolism, loss of long-term potentiation (LTP) and neuronal cell death in a rat model of SAH. SAH in rats was created by injection of 300 μl non-heparinized autologous blood into the pre-Chiasmatic Cistern. Clazosentan, 10mg/kg bolus, or vehicle control was administered 1h after SAH intravenously, followed by a continuous infusion (1mg/kg/h) into the jugular vein using an osmotic pump. Rats treated with clazosentan had less large-artery vasospsam compared to vehicle-treated controls. However, clazosentan did not prevent the formation of microthromboemboli, neuronal cell death and degeneration and loss of LTP, suggesting there is a dissociation between large-artery angiographic vasospasm and other secondary complications of SAH. This result suggests that alleviation of angiographic vasospasm alone may not be sufficient to prevent other secondary complications or that off-target drug effects after systemic administration of clazosentan counteract the beneficial effects on angiographic vasospasm.
Tamotsu Matsuda - One of the best experts on this subject based on the ideXlab platform.
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Urokinase Cisternal Irrigation Therapy for Prevention of Symptomatic Vasospasm After Aneurysmal Subarachnoid Hemorrhage A Study of Urokinase Concentration and the Fibrinolytic System
Stroke, 2000Co-Authors: Tatsuya Sasaki, Namio Kodama, Masahisa Kawakami, Masahiro Sato, Jun Asari, Yoshiharu Sakurai, Kazuo Watanabe, Takehide Onuma, Tamotsu MatsudaAbstract:Background and Purpose—Cisternal irrigation therapy with urokinase (UK) was performed in multiple institutions to prevent symptomatic vasospasm. The efficacy and safety of this therapy were evaluated, and the optimal concentration of UK was estimated. Methods—This therapy was performed in 28 patients who underwent surgery within 72 hours of the onset of severe subarachnoid hemorrhage (Fisher’s group 3, CT number [Hounsfield units] >60). After the aneurysm was clipped, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally and in the prepontine or Chiasmatic Cistern (outlet). Lactated Ringer’s solution with UK (30, 60, or 120 IU/mL) was infused at a rate of 30 mL/h. The presence of symptomatic vasospasm was evaluated by changes in the clinical symptoms and the presence of a new low-density area on CT scan. Drained irrigation fluid and peripheral blood were examined chronologically to evaluate the fibrinolytic system. Results—Symptomatic vasospasm was observed transiently in 3 cases (10.7%...
Gang Chen - One of the best experts on this subject based on the ideXlab platform.
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Tumor necrosis factor receptor-associated factor 6 participates in early brain injury after subarachnoid hemorrhage in rats through inhibiting autophagy and promoting oxidative stress.
Journal of neurochemistry, 2017Co-Authors: Yang Dou, Zhong Wang, Haitao Shen, Dongxia Feng, Xiaodi Tian, Jian Zhang, Gang ChenAbstract:Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a member of the TRAF family and an important multifunctional intracellular adaptin of the tumor necrosis factor superfamily and toll/IL-1 receptor (TIR) superfamily. TRAF6 has been studied in several central nervous system diseases, including ischemic stroke, traumatic brain injury, and neurodegenerative diseases, but its role in subarachnoid hemorrhage (SAH) has not been fully illustrated. This study was designed to explore changes of expression level and potential roles and mechanisms of TRAF6 in early brain injury (EBI) after SAH using a Sprague–Dawley rat model of SAH induced in 0.3 mL non-heparinized autologous arterial blood injected into the pre-Chiasmatic Cistern. First, compared with the sham group, we found that the expression levels of TRAF6 increased gradually and peaked at 24 h after SAH. Second, the results showed that application of TRAF6 over-expression plasmid and genetic silencing siRNA could increase or decrease expression of TRAF6, respectively, and severely exacerbate or relieve EBI after SAH, including neuronal death, brain edema, and blood–brain barrier injury. Meanwhile, the levels of autophagy and oxidative stress were reduced and increased separately. Finally, GFP-TRAF6-C70A, which is a TRAF6 mutant that lacks E3 ubiquitin ligase activity, was used to explore the mechanism of TRAF6 in SAH, and the results showed that EBI and oxidative stress were reduced, but the levels of autophagy were increased under this condition. Collectively, these results indicated that TRAF6 affected the degree of EBI after SAH by inhibiting autophagy and promoting oxidative stress.
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Dimethylfumarate alleviates early brain injury and secondary cognitive deficits after experimental subarachnoid hemorrhage via activation of Keap1-Nrf2-ARE system
Journal of Neurosurgery, 2015Co-Authors: Zhong Wang, Chengyuan Ji, Lingyun Wu, Gang ChenAbstract:OBJECT Oxidative stress and the inflammatory response are thought to promote brain damage in the setting of subarachnoid hemorrhage (SAH). Previous reports have shown that dimethylfumarate (DMF) can activate the Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2–antioxidant-responsive element (Keap1-Nrf2-ARE) system in vivo and in vitro, which leads to the downregulation of oxidative stress and inflammation. The aim of this study was to evaluate the potential neuroprotective effect of DMF on SAH-induced brain injury in rats. METHODS Rats were subjected to SAH by the injection of 300 μl of autologous blood into the Chiasmatic Cistern. Rats in a DMF-treated group were given 15 mg/kg DMF twice daily by oral gavage for 2 days after the onset of SAH. Cortical apoptosis, neural necrosis, brain edema, blood-brain barrier impairment, learning deficits, and changes in the Keap1-Nrf2-ARE pathway were assessed. RESULTS Administration of DMF significantly ameliorated the early brain injur...
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Expression of synaptosomal-associated protein-25 in the rat brain after subarachnoid hemorrhage.
Neural regeneration research, 2013Co-Authors: Gang Chen, Yang Jia, Zhong WangAbstract:Synaptosomal-associated protein-25 is an important factor for synaptic functions and cognition. In this study, subarachnoid hemorrhage models with spatial learning disorder were established through a blood injection into the Chiasmatic Cistern. Immunohistochemical staining and western blot analysis results showed that synaptosomal-associated protein-25 expression in the temporal lobe, hippocampus, and cerebellum significantly lower at days 1 and 3 following subarachnoid morrhage. Our findings indicate that synaptosomal-associated protein-25 expression was down-regulated in the rat brain after subarachnoid hemorrhage.
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Different effects of clazosentan on consequences of subarachnoid hemorrhage in rats.
Brain Research, 2011Co-Authors: Gang Chen, Mohammed Sabri, Asma Tariq, Hyojin Jeon, Elaine J.y. Tang, Katarina Lakovic, Hoyee Wan, R. Loch MacdonaldAbstract:One of the major complications after subarachnoid hemorrhage (SAH) is angiographic vasospasm in the large arteries at the base of the brain. However, a clinical trial of clazosentan demonstrated a 65% relative risk reduction in angiographic vasospasm but no effect on mortality or clinical outcome, raising questions about the role of angiographic vasospasm played in outcome after SAH. The purpose of this study was to determine if reducing or reversing angiographic vasospasm with clazosentan reduced other secondary complications such as microthromboembolism, loss of long-term potentiation (LTP) and neuronal cell death in a rat model of SAH. SAH in rats was created by injection of 300 μl non-heparinized autologous blood into the pre-Chiasmatic Cistern. Clazosentan, 10mg/kg bolus, or vehicle control was administered 1h after SAH intravenously, followed by a continuous infusion (1mg/kg/h) into the jugular vein using an osmotic pump. Rats treated with clazosentan had less large-artery vasospsam compared to vehicle-treated controls. However, clazosentan did not prevent the formation of microthromboemboli, neuronal cell death and degeneration and loss of LTP, suggesting there is a dissociation between large-artery angiographic vasospasm and other secondary complications of SAH. This result suggests that alleviation of angiographic vasospasm alone may not be sufficient to prevent other secondary complications or that off-target drug effects after systemic administration of clazosentan counteract the beneficial effects on angiographic vasospasm.
Mohammed Sabri - One of the best experts on this subject based on the ideXlab platform.
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Dissociation of Vasospasm and Secondary Effects of Experimental Subarachnoid Hemorrhage by Clazosentan
Stroke, 2011Co-Authors: Mohammed Sabri, R. Loch MacdonaldAbstract:Background and Purpose—Endothelin receptor antagonists such as clazosentan decrease large-artery vasospasm after experimental and clinical subarachnoid hemorrhage. We used clazosentan to gain insight into the pathophysiology of subarachnoid hemorrhage by determining if decreasing vasospasm is associated with alleviation of other secondary complications of subarachnoid hemorrhage such as oxidative stress, endothelial nitric oxide synthase dysfunction, microthromboembolism, and neuronal injury. Methods—Mice were subjected to subarachnoid hemorrhage by injection of blood into the Chiasmatic Cistern. They were treated with clazosentan or vehicle by continuous intraperitoneal infusion for 48 hours. Middle cerebral artery vasospasm, superoxide anion radical, peroxynitrite, microthromboemboli, endothelial nitric oxide synthase uncoupling, cerebral blood flow, neuronal injury, and mortality were assessed. Results—Clazosentan preserved cerebral blood flow, alleviated vasospasm, and decreased mortality but did not ...
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Different effects of clazosentan on consequences of subarachnoid hemorrhage in rats.
Brain Research, 2011Co-Authors: Gang Chen, Mohammed Sabri, Asma Tariq, Hyojin Jeon, Elaine J.y. Tang, Katarina Lakovic, Hoyee Wan, R. Loch MacdonaldAbstract:One of the major complications after subarachnoid hemorrhage (SAH) is angiographic vasospasm in the large arteries at the base of the brain. However, a clinical trial of clazosentan demonstrated a 65% relative risk reduction in angiographic vasospasm but no effect on mortality or clinical outcome, raising questions about the role of angiographic vasospasm played in outcome after SAH. The purpose of this study was to determine if reducing or reversing angiographic vasospasm with clazosentan reduced other secondary complications such as microthromboembolism, loss of long-term potentiation (LTP) and neuronal cell death in a rat model of SAH. SAH in rats was created by injection of 300 μl non-heparinized autologous blood into the pre-Chiasmatic Cistern. Clazosentan, 10mg/kg bolus, or vehicle control was administered 1h after SAH intravenously, followed by a continuous infusion (1mg/kg/h) into the jugular vein using an osmotic pump. Rats treated with clazosentan had less large-artery vasospsam compared to vehicle-treated controls. However, clazosentan did not prevent the formation of microthromboemboli, neuronal cell death and degeneration and loss of LTP, suggesting there is a dissociation between large-artery angiographic vasospasm and other secondary complications of SAH. This result suggests that alleviation of angiographic vasospasm alone may not be sufficient to prevent other secondary complications or that off-target drug effects after systemic administration of clazosentan counteract the beneficial effects on angiographic vasospasm.
Tatsuya Sasaki - One of the best experts on this subject based on the ideXlab platform.
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Urokinase Cisternal Irrigation Therapy for Prevention of Symptomatic Vasospasm After Aneurysmal Subarachnoid Hemorrhage A Study of Urokinase Concentration and the Fibrinolytic System
Stroke, 2000Co-Authors: Tatsuya Sasaki, Namio Kodama, Masahisa Kawakami, Masahiro Sato, Jun Asari, Yoshiharu Sakurai, Kazuo Watanabe, Takehide Onuma, Tamotsu MatsudaAbstract:Background and Purpose—Cisternal irrigation therapy with urokinase (UK) was performed in multiple institutions to prevent symptomatic vasospasm. The efficacy and safety of this therapy were evaluated, and the optimal concentration of UK was estimated. Methods—This therapy was performed in 28 patients who underwent surgery within 72 hours of the onset of severe subarachnoid hemorrhage (Fisher’s group 3, CT number [Hounsfield units] >60). After the aneurysm was clipped, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally and in the prepontine or Chiasmatic Cistern (outlet). Lactated Ringer’s solution with UK (30, 60, or 120 IU/mL) was infused at a rate of 30 mL/h. The presence of symptomatic vasospasm was evaluated by changes in the clinical symptoms and the presence of a new low-density area on CT scan. Drained irrigation fluid and peripheral blood were examined chronologically to evaluate the fibrinolytic system. Results—Symptomatic vasospasm was observed transiently in 3 cases (10.7%...