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MCAO recanalization

Keita Yamauchi, Yusuke Nakano, Takahiko Imai, Toshinori Takagi, Kazuhiro Tsuruma, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
Recanalization of occluded vessels leads to ischemia-reperfusion injury (IRI), with oxidative stress as one of the main causes of injury, despite the fact that recanalization therapy is the most effective treatment for ischemic stroke. The nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the transcription factors which has an essential role in protection against oxidative stress. RS9 is a novel Nrf2 activator obtained from bardoxolone methyl (BARD), an Nrf2 activator that has already been tested in a clinical trial, using a biotransformation technique...
October 1, 2016: Neuroscience
Lei Feng, Jun Liu, Yunzhen Liu, Jian Chen, Chunhai Su, Chuanfeng Lv, Yuzhen Wei
The aims of the present study were to establish a model of embolic stroke in rabbits and to evaluate the efficacy and safety of intra-arterially administered tirofiban combined with urokinase thrombolysis. The middle cerebral artery occlusion model (MCAO) of embolic stroke was established in New Zealand rabbits via an autologous clot. The model rabbits were allocated at random into four groups: Tirofiban group (T group), urokinase group (UK group), tirofiban and urokinase group (T + UK group) and the control group (C group)...
March 2016: Experimental and Therapeutic Medicine
Alexandra S Gersing, Andrea M Faymonville, Benedikt J Schwaiger, Frank Leypoldt, Susanne Siemonsen, Claus Zimmer, Tim Magnus, Jens Fiehler
BACKGROUND: Oxyhemoglobin-sensitive sequences, namely T2*, can indirectly depict changes in oxygen extraction. Purpose of this study was to investigate the dynamics of T2* changes in ischemic tissue. NEW METHOD: We investigated earliest temporo-spatial dynamics within ischemic tissue, measured with quantitative T2* imaging in the histologically defined infarct core and surrounding surviving tissue. Middle cerebral artery occlusion (MCAO) was induced by a filament model in mice...
February 1, 2016: Journal of Neuroscience Methods
Jean-Philippe Desilles, Stephane Loyau, Varouna Syvannarath, Jaime Gonzalez-Valcarcel, Marie Cantier, Liliane Louedec, Bertrand Lapergue, Pierre Amarenco, Nadine Ajzenberg, Martine Jandrot-Perrus, Jean-Baptiste Michel, Benoit Ho-Tin-Noe, Mikael Mazighi
BACKGROUND AND PURPOSE: Downstream microvascular thrombosis (DMT) is known to be a contributing factor to incomplete reperfusion in acute ischemic stroke. The aim of this study was to determine the timing of DMT with intravital imaging and to test the hypothesis that intravenous alteplase infusion could reduce DMT in a transient middle cerebral artery occlusion (MCAO) rat stroke model. METHODS: Rats were subjected to 60-minute transient MCAO. Alteplase (10 mg/kg) was administered 30 minutes after the beginning of MCAO...
November 2015: Stroke; a Journal of Cerebral Circulation
Atsuhiko Toyoshima, Takao Yasuhara, Masahiro Kameda, Jun Morimoto, Hayato Takeuchi, Feifei Wang, Tatsuya Sasaki, Susumu Sasada, Aiko Shinko, Takaaki Wakamori, Mihoko Okazaki, Akihiko Kondo, Takashi Agari, Cesario V Borlongan, Isao Date
OBJECTIVE: Intra-arterial stem cell transplantation exerts neuroprotective effects for ischemic stroke. However, the optimal therapeutic time window and mechanisms have not been completely understood. In this study, we investigated the relationship between the timing of intra-arterial transplantation of allogeneic mesenchymal stem cells (MSCs) in ischemic stroke model in rats and its efficacy in acute phase. METHODS: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes...
2015: PloS One
Sohail Ejaz, David J Williamson, Ulf Jensen-Kondering, Tahir Ahmed, Steve J Sawiak, Jean-Claude Baron
INTRODUCTION AND OBJECTIVES: Selective neuronal loss (SNL) in the reperfused penumbra may impact clinical recovery and is thus important to investigate. Brief proximal middle cerebral artery occlusion (MCAo) results in predominantly striatal SNL, yet cortical damage is more relevant given its behavioral implications and that thrombolytic therapy mainly rescues the cortex. Distal temporary MCAo (tMCAo) does target the cortex, but the optimal occlusion duration that results in isolated SNL has not been determined...
2015: Frontiers in Neurology
Michael Maniskas, Gregory Bix, Justin Fraser
With continuing disconnect between laboratory stroke treatment models and clinical stroke therapy, we propose a novel experimental model to study stroke and vessel recanalization that mirrors acute management of large vessel stroke, with concomitant directed pharmacotherapy. Using the tandem transient ipsilateral common carotid/middle cerebral artery occlusion (MCAO) model to induce stroke in mice we then added selective intra-arterial (IA) drug administration for directed pharmacotherapy. The IA model uses micro-angio tubing placed at the bifurcation of the CCA to selectively administer the drug to the internal carotid distribution...
January 30, 2015: Journal of Neuroscience Methods
Zhihua Sun, Yingmin Chen, Jing Zhang, Hong Guo, Yunting Zhang
OBJECTIVE: To explore the application of temperature measurement technique by ¹H magnetic resonance spectroscopy (MRS) in an ischemia monkey model. METHODS: A MRI-compatible thermostatic control system was developed. And the equation was corrected between brain temperature and the chemical shift of N-acetyl-L-aspartic acid (NAA) through in vitro experiment. The normal brain temperature of monkey brain was measured. And a monkey model of middle cerebral artery occlusion (MCAO) and reperfusion was established...
August 5, 2014: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Daisuke Shimbo, Takeo Abumiya, Hideo Shichinohe, Naoki Nakayama, Ken Kazumata, Kiyohiro Houkin
Despite successful revascularization, reperfusion after prolonged ischemia causes ischemia reperfusion (I/R) injury. Recruitment and activation of neutrophils is thought to be a key event causing I/R injury. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier without neutrophils, could reduce I/R injury in a rat transient middle cerebral artery occlusion (MCAO) model. Male Sprague-Dawley rats were subjected to 2-h MCAO and then were divided into three groups: (1) LEH group (n=7) infused with LEH (Hb concentration of 6g/dl, 10ml/kg/h) through the recanalized internal carotid artery for 2h, (2) vehicle group (n=8) infused with saline (10ml/kg/h) in the same manner as the LEH group, and (3) control group (n=9) subjected to recanalization only...
March 20, 2014: Brain Research
Saema Ansar, Eva Chatzikonstantinou, Rushani Thiagarajah, Laurent Tritschler, Marc Fatar, Michael G Hennerici, Stephen Meairs
BACKGROUND: A recent study suggests that patients with persistent occlusion of the middle cerebral artery (MCA) following treatment with recombinant tissue plasminogen activator (rt-PA) have better outcomes than patients with MCA occlusion not receiving rt-PA. We performed a study to elucidate possible mechanisms of this finding in a new model of thromboembolic stroke closely mimicking human pathophysiology. METHODS: Thromboembolic stroke was induced by local injection of thrombin directly into the right MCA of C57 black/6J mice...
2014: PloS One
Saema Ansar, Eva Chatzikonstantinou, Anja Wistuba-Schier, Silvia Mirau-Weber, Marc Fatar, Michael G Hennerici, Stephen Meairs
This study characterizes a new model of thromboembolic stroke of the middle cerebral artery in C57 black/6J mice, thus offering an opportunity to use the model for studying ischemic stroke in transgenic mice. Thromboembolic stroke was induced by local injection of either 1.5 or 3.0 UI of thrombin directly into the right MCA of C57 black/6J mice. Cerebral blood flow (CBF) velocity was measured continuously by laser Doppler flowmetry, which allowed documentation of both MCA occlusion and of spontaneous recanalization...
August 2014: Translational Stroke Research
Roderic H Fabian, Thomas A Kent
Hyperglycemia worsens outcome in stroke patients and in a variety of stroke models, most prominently following prolonged ischemia and reperfusion. Vascular dysfunction has been associated with this worsened outcome, manifested by reduced reperfusion cerebral blood flow (CBF), as well as increased hemorrhagic transformation, edema, and mortality. The phenomenon of "uncoupling" of endothelial nitric oxide synthase (eNOS) has been associated with hyperglycemia in the periphery and results in a dysfunctional eNOS-generating superoxide radical ([Formula: see text]) in lieu of nitric oxide (NO)...
December 2012: Translational Stroke Research
Ian R Winship, Glenn A Armitage, Gomathi Ramakrishnan, Bin Dong, Kathryn G Todd, Ashfaq Shuaib
Collateral circulation provides an alternative route for blood flow to reach ischemic tissue during a stroke. Blood flow through the cerebral collaterals is a critical predictor of clinical prognosis after stroke and response to recanalization, but data on collateral dynamics and collateral therapeutics are lacking. Here, we investigate the efficacy of a novel approach to collateral blood flow augmentation to increase collateral circulation by optically recording blood flow in leptomeningeal collaterals in a clinically relevant model of ischemic stroke...
January 2014: Journal of Cerebral Blood Flow and Metabolism
Brad A Sutherland, Alastair M Buchan
Recanalization of an occluded vessel with recombinant tissue plasminogen activator is an effective strategy for treating acute ischemic stroke. Recombinant tissue plasminogen activator is administered as alteplase, a formulation containing many excipients including L-arginine, the substrate for nitric oxide production. Most studies fail to compare the effects of alteplase on brain injury to its L-arginine carrier solution. This study aimed to verify the previously reported detrimental effects of alteplase after cerebral ischemia and delineate the contribution of L-arginine...
November 2013: Journal of Cerebral Blood Flow and Metabolism
Koji Murakami, Motohisa Suzuki, Noriko Suzuki, Kazuhiro Hamajo, Tetsuya Tsukamoto, Masato Shimojo
Some occluded arteries of acute ischemic stroke (AIS) patients are not recanalized, even if thrombolytic therapy is performed. Considering such clinical settings, we examined the potential cerebroprotective efficacy of TAK-937, a novel cannabinoid receptor agonist, in young adult and aged rats with a permanent middle cerebral artery occlusion (MCAO) model and conducted a combination study with TAK-937 and tissue type plasminogen activator (t-PA) in a rat thrombotic MCAO model. TAK-937 significantly reduced infarct volume when it was administered 3 and 5h after permanent MCAO in young adult rats...
August 14, 2013: Brain Research
Susanne Wegener, Judith Artmann, Andreas R Luft, Richard B Buxton, Michael Weller, Eric C Wong
After recanalization, cerebral blood flow (CBF) can increase above baseline in cerebral ischemia. However, the significance of post-ischemic hyperperfusion for tissue recovery remains unclear. To analyze the course of post-ischemic hyperperfusion and its impact on vascular function, we used magnetic resonance imaging (MRI) with pulsed arterial spin labeling (pASL) and measured CBF quantitatively during and after a 60 minute transient middle cerebral artery occlusion (MCAO) in adult rats. We added a 5% CO2 - challenge to analyze vasoreactivity in the same animals...
2013: PloS One
Christoph Beck, Bastian Cheng, Anna Krützelmann, Michael Rosenkranz, Christian Gerloff, Jens Fiehler, Götz Thomalla
Low recanalization rates and poor clinical outcome have been reported after intravenous thrombolysis (IV-tPA) in carotid-T occlusion (CTO). We studied clinical outcome and imaging findings of MRI-based intravenous thrombolysis in CTO. Data of patients with acute ischemic stroke and CTO treated with IV-tPA within 6 h of symptom onset based on MRI criteria were retrospectively analyzed. Vessel occlusion was defined based on MR angiography. Acute diffusion and perfusion lesion volumes and final infarct volumes after 3-7 days were delineated...
October 2012: Journal of Neurology
Qiang Shen, Fang Du, Shiliang Huang, Timothy Q Duong
The spatiotemporal dynamics of postischemic hyperperfusion (HP) remains incompletely understood. Diffusion, perfusion, T2, T1, angiographic, dynamic susceptibility-contrast magnetic resonance imaging (MRI) and magnetic resonance angiography were acquired longitudinally at multiple time points up to 7 days after stroke in rats subjected to 30-, 60-, and 90-minutes middle cerebral artery occlusion (MCAO). The spatiotemporal dynamics of postischemic HP was analyzed and compared with T1, T2 and blood-brain barrier (BBB) changes...
October 2011: Journal of Cerebral Blood Flow and Metabolism
Kutluay Uluç, Amrendra Miranpuri, Gregory C Kujoth, Erinç Aktüre, Mustafa K Başkaya
Stroke is the leading cause of disability and the third leading cause of death in adults worldwide. In human stroke, there exists a highly variable clinical state; in the development of animal models of focal ischemia, however, achieving reproducibility of experimentally induced infarct volume is essential. The rat is a widely used animal model for stroke due to its relatively low animal husbandry costs and to the similarity of its cranial circulation to that of humans. In humans, the middle cerebral artery (MCA) is most commonly affected in stroke syndromes and multiple methods of MCA occlusion (MCAO) have been described to mimic this clinical syndrome in animal models...
2011: Journal of Visualized Experiments: JoVE
Li Sun, Wei Zhou, Christian Mueller, Clemens Sommer, Sabine Heiland, Alexander T Bauer, Hugo H Marti, Roland Veltkamp
Hyperbaric oxygen (HBO) and normobaric hyperoxia (NBO) protect the brain parenchyma and the cerebral microcirculation against ischemia. We studied their effect on secondary hemorrhage after thrombolysis in two thromboembolic middle cerebral artery occlusion (MCAO) (tMCAO) models. Beginning 60 minutes after tMCAO with either thrombin-induced thromboemboli (TT) or calcium-induced thromboemboli (CT), spontaneously hypertensive rats (n=96) breathed either air, 100% O(2) (NBO), or 100% O(2) at 3 bar (HBO) for 1 hour...
September 2010: Journal of Cerebral Blood Flow and Metabolism
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