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MCAO recanalization

Y-J Yu, W Xiong
OBJECTIVE: To investigate the curative effect of tirofiban combined with recombinant tissue-plasminogen activator (rt-PA) selective intra-arterial thrombolysis on acute middle cerebral artery occlusion (MCAO). MATERIALS AND METHODS: A total of 60 adult male Japanese white rabbits weighing 2.5-3.0 kg were selected, and the acute cerebral infarction model was established via autologous thromboembolism of middle cerebral artery. Rabbits were randomly divided into 4 groups: tirofiban group (Ti group, 5 μg/kg, n=15), rt-PA group (rt-PA group, 2 mg/kg, n=15), tirofiban + rt-PA group (Ti + rt-PA group, 3 μg/kg Ti + 1 mg/kg rt-PA, n=15), and control group (Co group, n=15)...
May 2018: European Review for Medical and Pharmacological Sciences
Gang Zuo, Dongping Zhang, Rutao Mu, Haitao Shen, Xiang Li, Zhong Wang, Haiying Li, Gang Chen
Cerebral ischemia/reperfusion (I/R) injury is a critical factor leading to a poor prognosis for ischemic stroke patients. ω-3 fatty acid supplements taken as part of a daily diet have been shown to improve the prognosis of patients with ischemic stroke. In this study, we aimed to investigate the potential effects of resolvin D2 (RvD2), a derivative of ω-3 fatty acids, and its possible advantage on cerebral I/R injury in rats. Cerebral I/R caused by middle cerebral artery occlusion and reperfusion (MCAO/R) was established in Sprague-Dawley rats...
February 13, 2018: Molecular Brain
Wan-Wan Xu, Ying-Ying Zhang, Juan Su, Ao-Fei Liu, Kai Wang, Chen Li, Yun-E Liu, Yi-Qun Zhang, Jin Lv, Wei-Jian Jiang
Ischemia-reperfusion injury (IRI) is an important cause of adverse prognosis after recanalization in patients with acute occlusion of major intracranial artery (AOMIA). Here, we provided data indicating that gradual flow restoration (GFR) would be superior to rapid flow restoration (RFR) in alleviating cerebral IRIs in middle cerebral artery occlusion (MCAO) rats. A total of 94 MCAO rats with 15, 30 and 60-minute occlusion were randomly assigned to receive either GFR or RFR intervention. There were significant differences between GFR and RFR group in mean neurological severity score (1...
January 26, 2018: Scientific Reports
Estelle Rousselet, Anne Létondor, Bénédicte Menn, Yann Courbebaisse, Marie-Lise Quillé, Serge Timsit
Stroke is a devastating disorder that significantly contributes to death, disability and healthcare costs. In ischemic stroke, the only current acute therapy is recanalization, but the narrow therapeutic window less than 6 h limits its application. The current challenge is to prevent late cell death, with concomitant therapy targeting the ischemic cascade to widen the therapeutic window. Among potential neuroprotective drugs, cyclin-dependent kinase inhibitors such as (S)-roscovitine are of particular relevance...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
Junqiang Ma, Yonglie Ma, Bin Dong, Mischa V Bandet, Ashfaq Shuaib, Ian R Winship
Collateral circulation is a key variable determining prognosis and response to recanalization therapy during acute ischemic stroke. Remote ischemic perconditioning (RIPerC) involves inducing peripheral ischemia (typically in the limbs) during stroke and may reduce perfusion deficits and brain damage due to cerebral ischemia. In this study, we directly investigated pial collateral flow augmentation due to RIPerC during distal middle cerebral artery occlusion (MCAo) in rats. Blood flow through pial collaterals between the anterior cerebral artery (ACA) and the MCA was assessed in male Sprague Dawley rats using in vivo laser speckle contrast imaging (LSCI) and two photon laser scanning microscopy (TPLSM) during distal MCAo...
August 2017: Journal of Cerebral Blood Flow and Metabolism
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
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