Abstract W P209: Development of a Useful Brain Ischemic Stroke Model via a Transient Occlusion of Middle Cerebral Artery in the Nonhuman Primate

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Eiketsu Sho ◽  
Zhenghua Zhu ◽  
Yuchao Zhao ◽  
Jiqiao Chen ◽  
Daomei He ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Nonhuman Primate ◽  
Stroke Model ◽  
Cynomolgus Monkeys ◽  
Stroke Research ◽  
Reperfusion Period ◽  
The Brain

Objectives: Most experimental stroke research is carried out in rodents, but given differences between rodents and human, the nonhuman primate (NHP) models may provide a valuable tool to study the clinical therapy. We developed a surgical method for transient occlusion of the middle cerebral artery (MCA-M1) in the Cynomolgus monkeys to evaluate the MCA territory blood flow, the model stability, animal clinical neurological behavior, morphology changes under magnetic resonance imaging (MRI) and histopathology. Methods: The left brain sylvian fissure was exposed by a small fronto-temporal craniotomy. The MCA-M1 was exposed by microsurgical dissection and clipped for 4 hours. The brain blood flow was measured in the MCA territory during the ischemia period and early phase of reperfusion period. The clinical neurological examinations and MRI were carried out at regular post-operative course till 4 weeks of stroke. Results: During MCA occlusion, the MCA territory blood flow was decreased significantly in 80%. This territory was reflowed right after reperfusion and showed an overload in about 20% over pre ischemia flow within 1hr after reperfusion and gradually returned to previous flow (Fig 1). Animal neurological behavior changed significantly within 1 week and became a steady status of neurological impairment. MRI demonstrated extensive MCA territory infarction. Histologically, at the end of 4 week stroke the brain showed a clear board of glia proliferation between infarct and normal brain tissue. Conclusion: These results indicate a stable ischemic stroke model in cynomolgus monkeys after complete MCA-M1 occlusion, which will be a useful NHP stroke model for stroke research and the clinical therapeutic studies. Fig 1 Changes in MCA territory blood flow during ischemia-reperfusion period

Abstract 166: Endothelial Overexpression of LOX-1 Increases Stroke Size in vivo

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Alexander Akhmedov ◽  
Remo D Spescha ◽  
Francesco Paneni ◽  
Giovani G Camici ◽  
Thomas F Luescher
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Endothelial Dysfunction ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Oxidized Ldl ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion ◽  
The Brain

Background— Stroke is one of the most common causes of death and long term disability worldwide primarily affecting the elderly population. Lectin-like oxidized LDL receptor 1 (LOX-1) is the receptor for oxidized LDL identified in endothelial cells. Binding of OxLDL to LOX-1 induces several cellular events in endothelial cells, such as activation of transcription factor NF-kB, upregulation of MCP-1, and reduction in intracellular NO. Accumulating evidence suggests that LOX-1 is involved in endothelial dysfunction, inflammation, atherogenesis, myocardial infarction, and intimal thickening after balloon catheter injury. Interestingly, a recent study demonstrated that acetylsalicylic acid (aspirin), which could prevent ischemic stroke, inhibited Ox-LDL-mediated LOX-1 expression in human coronary endothelial cells. The expression of LOX-1 was increased at a transient ischemic core site in the rat middle cerebral artery occlusion model. These data suggest that LOX-1 expression induces atherosclerosis in the brain and is the precipitating cause of ischemic stroke. Therefore, the goal of the present study was to investigate the role of endothelial LOX-1 in stroke using experimental mouse model. Methods and Results— 12-week-old male LOX-1TG generated recently in our group and wild-type (WT) mice were applied for a transient middle cerebral artery occlusion (MCAO) model to induce ischemia/reperfusion (I/R) brain injury. LOX-1TG mice developed 24h post-MCAO significantly larger infarcts in the brain compared to WT (81.51±8.84 vs. 46.41±10.13, n=7, p < 0.05) as assessed morphologically using Triphenyltetrazolium chloride (TTC) staining. Moreover, LOX-1TG showed higher neurological deficit in RotaRod (35.57±8.92 vs. 66.14±10.63, n=7, p < 0.05) and Bederson tests (2.22±0.14 vs. 1.25±0.30, n=9-12, p < 0.05) - two experimental physiological tests for neurological function. Conclusions— Thus, our data suggest that LOX-1 plays a critical role in the ischemic stroke when expressed at unphysiological levels. Such LOX-1 -associated phenotype could be due to the endothelial dysfunction. Therefore, LOX-1 may represent novel therapeutic targets for preventing ischemic stroke.

scholarly journals Modeling of the Human Cerebral Collateral Circulation: Evaluation of the Impact on the Cerebral Perfusion in Case of Ischemic Stroke

2019 ◽  
Vol 5 (1) ◽  
pp. 533-536
Author(s):  
Lorena Krames ◽  
Rosa Daschner ◽  
Yannick Lutz ◽  
Axel Loewe ◽  
Olaf Dössel ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Collateral Circulation ◽  
Treatment Method ◽  
Developed Countries ◽  
Extended Model ◽  
Flow Through ◽  
The Impact

AbstractStroke is the third-most cause of death in developed countries. A new promising treatment method in case of an ischemic stroke is selective intracarotid blood cooling combined with mechanical artery recanalization. However, the control of the treatment requires invasive or MRI-assisted measurement of cerebral temperature. An auspicious alternative is the use of computational modeling. In this work, we extended an existing 1D hemodynamics model including the characteristics of the anterior, middle and posterior cerebral artery. Furthermore, seven ipsilateral anastomoses were additionally integrated for each hemisphere. A potential stenosis was placed into the M1 segment of the middle cerebral artery, due to the highest risk of occlusion there. The extended model was evaluated for various degrees of collateralization (“poor”, “partial” and “good”) and degrees of stenosis (0%, 50%, 75% and 99.9%). Moreover, cerebral autoregulation was considered in the model. The higher the degree of collateralization and the degree of stenosis, the higher was the blood flow through the collaterals. Hence, a patient with a good collateralization could compensate a higher degree of occlusion and potentially has a better outcome after an ischemic stroke. For a 99.9% stenosis, an increased summed mean blood flow through the collaterals of +97.7% was predicted in case of good collateralization. Consequently, the blood supply via the terminal branches of the middle cerebral artery could be compensated up to 44.4% to the physiological blood flow. In combination with a temperature model, our model of the cerebral collateral circulation can be used for tailored temperature prediction for patients to be treated with selective therapeutic hypothermia.

Changes in cerebral blood flow and oxygen metabolism during moderate hypothermia in patients with severe middle cerebral artery infarction

2000 ◽  
Vol 8 (5) ◽  
pp. 1-4 ◽  
Author(s):  
Emanuela Keller ◽  
Thorsten Steiner ◽  
Javier Fandino ◽  
Stefan Schwab ◽  
Werner Hacke
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Mild Hypothermia ◽  
Indicator Dilution ◽  
Dilution Method ◽  
Moderate Hypothermia ◽  
Double Indicator Dilution

Object Moderate hypothermia has been reported to be effective in the treatment of postischemic brain edema. The effect of hypothermia on cerebral hemodynamics is a matter of controversial discussion in literature. Clinical studies have yet to be performed in patients with ischemic stroke after induction of hypothermia. Methods Measurements during mild hypothermia (33–34°C) were made in six patients with severe ischemic stroke involving the middle cerebral artery territory. Hypothermia was induced as soon as possible and maintained for 48 to 72 hours. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were estimated by a new double-indicator dilution method. Measurements of CBF were made during normothermia, immediately after induction of hypothermia, at the end of hypothermia, and after rewarming. A total of 19 measurements of CBF and jugular bulb O2 saturation were made. Immediately after induction of hypothermia, CBF decreased in all patients. During late hypothermia, CBF improved in patients who survived but remained diminished in the two patients who died. Reduced CMRO2 levels were observed during all phases of hypothermia in all but one case. Conclusions Preliminary oberservations indicate that moderate hypothermia seems to reduce CMRO2 Immediately after induction of hypothermia, CBF may decrease in all patients. During late hypothermia CBF seems to recover in patients with good outcome but remains diminished in patients who die. Serial bedside CBF measurements with the new double-indicator dilution technique may be useful to describe cerebral hemodynamic characteristics in patients with severe ischemic stroke during hypothermia.

scholarly journals Endogenous THBD (Thrombomodulin) Mediates Angiogenesis in the Ischemic Brain—Brief Report

2020 ◽  
Vol 40 (12) ◽  
pp. 2837-2844 ◽  
Author(s):  
Jan Wenzel ◽  
Dimitrios Spyropoulos ◽  
Julian Christopher Assmann ◽  
Mahtab Ahmad Khan ◽  
Ines Stölting ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Soluble Form ◽  
Stroke Outcome ◽  
Brain Endothelial Cells ◽  
Ischemic Brain ◽  
Infarct Area ◽  
The Brain

Objective: THBD (thrombomodulin) is part of the anticoagulant protein C-system that acts at the endothelium and is involved in anti-inflammatory and barrier-stabilizing processes. A recombinant soluble form of THBD was shown to have protective effects in different organs, but how the endogenous THBD is regulated during ischemia, particularly in the brain is not known to date. The aim of this study was to investigate the role of THBD, especially in brain endothelial cells, during ischemic stroke. Approach and Results: To induce ischemic brain damage, we occluded the middle cerebral artery of mice. We found an increased endothelial expression of Thbd in the peri-infarct area, whereas in the core of the ischemic tissue Thbd expression was decreased compared with the contralateral side. We generated a novel Cre/loxP-based mouse line that allows for the inducible deletion of Thbd specifically in brain endothelial cells, which worsened stroke outcome 48 hours after middle cerebral artery occlusion. Unexpectedly, we found no signs of increased coagulation, thrombosis, or inflammation in the brain but decreased vessel diameters and impaired angiogenesis in the peri-infarct area that led to a reduced overall vessel length 1 week after stroke induction. Conclusions: Endogenous THBD acts as a protective factor in the brain during ischemic stroke and enhances vessel diameter and proliferation. These previously unknown properties of THBD could offer new opportunities to affect vessel function after ischemia and thereby improve stroke outcome.

scholarly journals Analysis of Thrombi Retrieved from Cerebral Arteries of Patients with Acute Ischemic Stroke.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 263-263
Author(s):  
Victor J. Marder ◽  
Dennis J. Chute ◽  
Sidney Starkman ◽  
Anna M. Abolian ◽  
Chelsea Kidwell ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Carotid Artery ◽  
Middle Cerebral Artery ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Clinical Consequence ◽  
Initiation Of Therapy ◽  
Stroke Center

Abstract To obtain insights into the pathogenesis of ischemic stroke, we analyzed thromboemboli and other occlusive material retrieved acutely from the cerebral arteries of patients. The experimental design was an observational study in 25 consecutive patients with acute ischemic stroke treated by endovascular mechanical thromboembolectomy. Patients with acute occlusion of a proximal cerebral artery, a disabling neurologic deficit, and either initiation of therapy within 8 hours of onset or initiation of therapy beyond 8 hours if imaging demonstrated substantial residual penumbral tissue at risk were treated at a tertiary Comprehensive Stroke Center (the UCLA Stroke Center). Thrombus was removed by an endovascular mechanical embolectomy device (Merci® Retriever System, Concentric Medical, Mountain View, CA) after placement by angiographic catheter into the occluded intracranial carotid artery, middle cerebral artery or vertebral-basilar artery under fluoroscopic guidance. Our results show that the large majority (20 of 25) of extracted thrombi have similar histologic architecture, a complex of layered, sometimes serpentine, lengths of fibrin:platelet deposits interspersed with linear streaks of nucleated cells. This histology was prevalent with both cardioembolic and atherosclerotic etiologies, indicating the same pathogenetic influences of blood flow and shear in thrombus formation. This histologic pattern among thrombi was present in both the internal carotid artery (ICA) and the middle cerebral artery (MCA). Clots composed uniformly of erythrocytes were uncommon (3 of 25) and were observed only with incomplete extractions, suggesting that sampling was of the proximal thrombus tail where post-occlusion thrombosis had occurred under conditions of stagnant flow. Calcifications or cholesterol were not present. Thrombus size, not histology, predicted the site of arterial occlusion, with no thrombus larger than 3 mm width causing stroke limited to the MCA and no thrombus larger than 5 mm width removed from the ICA. Fungus-containing thrombus was extracted from one patient who had mycotic valvular disease, and an unusual complication occurred in another case, namely, scraping of a small atheroma and attached intima from the MCA, albeit without clinical consequence. We conclude that thromboemboli that cause acute ischemic stroke are of similar, complex structure, regardless of macroscopic dimensions, and are similarly influenced by blood flow, whether the primary etiology is cardioembolic or atherosclerotic. Embolus size is the critical aspect that determines its ultimate destination, those of more than 5 mm width appearing to bypass the cerebral vessels entirely. The mixed fibrin:platelet pattern present in the preponderance of thromboemboli provides foundation for the success of both antiplatelet and anticoagulant treatment strategies in stroke prevention.

Abstract WP48: Relationship of Cerebral Blood Flow by Pseudo-continuous Arterial Spin Labeling and Stenosis in Middle Cerebral Artery Territory in Patients Evaluated for Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Eric Lai ◽  
Raja Rizal Azman Raja Aman ◽  
Hui Zhang ◽  
Pui-Wai Chiu ◽  
Queenie Chan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Arterial Spin Labeling ◽  
Spin Labeling ◽  
Arterial Stenosis ◽  
Vascular Territory

Purpose: Correlation of arterial stenosis with cortical and subcortical cerebral blood flow (CBF) in the middle cerebral artery (MCA) territory. Methods: 126 patients with acute cerebrovascular symptoms from March to June 2015 underwent MRI and MR Angiography (MRA) in a University hospital using a 3.0 Tesla scanner. Sequences included T1W, T2W, FLAIR, DWI, MRA, Pseudocontinuous Arterial Spin Labeling (pcASL, post-labeling delay 1.525 s). 13 patients (corrupted pcASL data) were excluded, with 113 patients (mean age: 67.74±14.19) evaluated (61 acute ischemic stroke, 52 patients transient ischemic attack). Institutionally developed software was used to determine CBF. MCA stenosis was graded into 4 categories by a neuroradiologist: 0 (no stenosis), 1 (mild <50%), 2 (moderate 50-70%) and 3 (severe >70%). Mean and standard deviation of MCA categories (leptomeningeal and perforating) CBF and corresponding degree of MCA stenosis were measured. Spearman correlation coefficients between CBF of cortical and subcortical regions and degree of MCA stenoses were calculated using SPSS (version 23.0). Results: The table showed the descriptive statistics. There was significant correlation between CBF of cortical region of MCA vascular territory and degree of stenosis of MCA in both left (r s = -0.296, p =0.001) and right (r s = -0.306, p =0.001) side. In the contrary, there was no correlation between subcortical CBF of MCA vascular territory and degree of stenosis of MCA in both sides. Conclusion: pcASL is a feasible non-invasive method to measure CBF in clinical setting. In MCA territory, the cortical blood flow correlated (fairly) with large vessel stenosis but not subcortical flow. We conclude that cortical CBF correlated with large artery stenosis, though being attenuated by collateral blood supply. No such relationship in subcortical CBF might be due to differential grey and white matter CBF flow, variable MCA stenotic location, and perforators originating from other territories.

Abstract 2716: Patients with Leukoaraiosis Have Poor Recruitment of Collaterals After Middle Cerebral Artery Occlusion

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Ethem Murat Arsava ◽  
Osman Melih Topcuoglu ◽  
Erhan Akpinar ◽  
Kader K Oguz ◽  
Mehmet Akif Topcuoglu
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Collateral Circulation ◽  
Artery Occlusion ◽  
Poor Recruitment ◽  
Collateral Vessels ◽  
Cerebral Artery Occlusion

Background: Previous studies have shown reduced penumbral salvage in ischemic stroke patients with higher leukoaraisosis (LA) volume. Although unproven, decreased cerebral vessel density and diminished capacity of cerebral vessels to dilate in response to reduced blood flow in severe LA, are considered among the factors that might explain the association between LA burden and infarct growth in ischemic stroke. Both of these factors, in theory, might negatively affect the extent of collateral blood flow, an important predictor of tissue and clinical outcome in patients with acute ischemic stroke. In this study, we therefore analyzed whether extent of LA adversely affected the degree of collateral circulation in a cohort of patients presenting with middle cerebral artery occlusion. Methods: We retrospectively analyzed a consecutive series of patients admitted with a diagnosis of middle cerebral artery occlusion. Computed tomography angiography source images (CTA-SI) were used to assess the degree of collateral circulation, based on a previously validated scoring system which grades collateral vessels in the sylvian fissure and leptomeningeal convexity separately on a scale from 1 to 5, with 1 being the worst and 5 the best. The extent of LA was determined on FLAIR images by using the Fazekas scale. Multivariate analysis was used to explore the relationship between extent of LA and degree of collateral circulation, adjusted for other covariates like age, gender, vascular risk factors and time from symptom onset to CTA imaging. Results: A total of 51 patients (31 female, 20 male) were included into the study. LA severity was significantly and negatively correlated with the degree of collateral supply (r=-0.31, p=0.03). LA severity (OR 5.9, 95%CI 1.5-24.0) and history of prior stroke (OR 7.8, 95%CI 1.0-59.3) were the only significant variables associated with insufficient collaterals (defined as a combined sylvian and lepotmeningeal collateral score of 5 or less) in the multivariate logistic regression analysis. Conclusion: Patients with higher LA burden have a poor recruitment of collateral vessels after middle cerebral artery occlusion. This association might contribute to reduced penumbral salvage and increased susceptibility to infarct growth observed in patients with severe LA.

scholarly journals Middle Cerebral Artery Occlusion Model in Rodents: Methods and Potential Pitfalls

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Fudong Liu ◽  
Louise D. McCullough
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Stroke Model ◽  
Occlusion Model ◽  
Cerebral Artery Occlusion ◽  
Paradoxical Results ◽  
Age And Sex

A variety of animal models have been developed for modeling ischemic stroke. The middle cerebral artery occlusion (MCAO) model has been utilized extensively, especially in rodents. While the MCAO model provides stroke researchers with an excellent platform to investigate the disease, controversial or even paradoxical results are occasionally seen in the literature utilizing this model. Various factors exert important effects on the outcome in this stroke model, including the age and sex of the animal examined. This paper discusses emerging information on the effects of age and sex on ischemic outcomes after MCAO, with an emphasis on mouse models of stroke.

scholarly journals Eyeballing stroke: Blood flow alterations in the eye and visual impairments following transient middle cerebral artery occlusion in adult rats

2020 ◽  
Vol 29 ◽  
pp. 096368972090580
Author(s):  
Jea-young Lee ◽  
Vanessa Castelli ◽  
Brooke Bonsack ◽  
Julián García-Sánchez ◽  
Chase Kingsbury ◽  
...  
Keyword(s):  
Blood Flow ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Laser Doppler ◽  
Adult Rats ◽  
Visual Deficits ◽  
Cerebral Artery Occlusion ◽  
The Brain

Middle cerebral artery occlusion in rodents remains a widely used model of ischemic stroke. Recently, we reported the occurrence of retinal ischemia in animals subjected to middle cerebral artery occlusion, owing in part to the circulatory juxtaposition of the ophthalmic artery to the middle cerebral artery. In this study, we examined the eye hemodynamics and visual deficits in middle cerebral artery occlusion-induced stroke rats. The brain and eye were evaluated by laser Doppler at baseline (prior to middle cerebral artery occlusion), during and after middle cerebral artery occlusion. Retinal function-relevant behavioral and histological outcomes were performed at 3 and 14 days post-middle cerebral artery occlusion. Laser Doppler revealed a typical reduction of at least 80% in the ipsilateral frontoparietal cortical area of the brain during middle cerebral artery occlusion compared to baseline, which returned to near-baseline levels during reperfusion. Retinal perfusion defects closely paralleled the timing of cerebral blood flow alterations in the acute stages of middle cerebral artery occlusion in adult rats, characterized by a significant blood flow defect in the ipsilateral eye with at least 90% reduction during middle cerebral artery occlusion compared to baseline, which was restored to near-baseline levels during reperfusion. Moreover, retinal ganglion cell density and optic nerve depth were significantly decreased in the ipsilateral eye. In addition, the stroke rats displayed eye closure. Behavioral performance in a light stimulus-mediated avoidance test was significantly impaired in middle cerebral artery occlusion rats compared to control animals. In view of visual deficits in stroke patients, closely monitoring of brain and retinal perfusion via laser Doppler measurements and examination of visual impairments may facilitate the diagnosis and the treatment of stroke, including retinal ischemia.

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