Name: reproducible motor deficit following aortic occlusion in a rat model of spinal cord ischemia
Uploaded: 2017-07-22T13:00:00.000+00:00
Duration: 8 min 10 s
Description: Watch this Scientific Journal Video about Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia at JoVE.com

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本议定书由首尔国立大学邦唐医院机构动物护理使用委员会批准。根据美国国家卫生研究院护理和使用实验动物的指南进行动物护理和实验。 手术准备<ol><li>在手术前，用无菌盐水冲洗导管以确保通畅。 </li><li>将加热毯放在手术台上，并用无菌悬垂盖住桌子。 </li><li>将雄性Sprague-Dawley大鼠（270-330g）放入具有3.0％-4.0％异氟烷的丙烯酸盒中，在100％氧气中。 </li><li>向大鼠的眼睛涂抹润滑剂。 </li><li>将大鼠放在手术台上仰卧位，并使用面罩连续给药吸入异氟烷（1.0％-2.5体积％），维持麻醉。 </li><li>放置直肠探针以监测和维持体温在37.0-38.0°C之间。 </l我&gt; </ol>股动脉导管<ol><li>使用Betadine和70％乙醇轻轻擦洗右腹股沟区域。 </li><li>在右腹股沟区域使用剪刀做一个2厘米水平的皮肤切口。 </li><li>使用牵开器，暴露外科手术。 </li><li>从周围静脉和神经解剖股动脉。使用弯曲的镊子和钝的镊子分离1 cm的动脉部分。 </li><li>使用4.0黑色丝线缝合，在动脉的近端和远端放置松绑，以最大化暴露。 </li><li>使用微型剪刀在股动脉上进行切口。 </li><li>插入2-Fr。气囊导管使用微镊子进入股动脉。将导管固定在离近端结扎导管头1厘米处的血管上，然后将远端结扎扎扎。 </li></ol>颈动脉导管<ol><li>用betad擦洗右前颈ine和70％乙醇，然后做皮肤切口。 </li><li>使用牵开器，暴露外科手术。分离动脉的1厘米部分，并用动脉近端和远端的丝线缝合松紧，以使暴露最大化。 </li><li>使用24 G静脉导管穿刺颈动脉，并将导管的近端1 cm推向心脏。 </li><li>用近端结扎固定导管，然后绑扎远端结扎。 </li><li>使用三通旋塞阀，将导管的远端连接到盐水填充的微管和外部储存器。 </li></ol> 4.尾动脉导管<ol><li>使用betadine和70％乙醇洗涤尾巴的腹侧，并制成2厘米的皮肤切口。 </li><li>从周围的结构解剖尾动脉，并使用弯曲的镊子和钝的镊子隔离1cm的动脉部分。 </li><li>使用4.0黑色丝线缝合，放松绑在动脉的近端和远端，以最大化曝光。 </li><li>使用24 G静脉导管穿刺尾动脉，并将导管推入动脉。 </li><li>将导管固定到血管（距离导管头约1厘米）与近端结扎，并绑定远端结扎。 </li><li>将导管的远端连接到动脉压监测装置。 </li></ol> 5.脊髓缺血诱导<ol><li>导管完成后，推进2气球导管进入下行胸主动脉，使得导管的尖端到达左锁骨下动脉。 </li><li>插入距离插入位置10厘米的深度。 </li><li>以100单位/ mL的浓度将150单位肝素注入颈动脉导管。 </li><li>用0.05 mL盐水充气导管球囊。 </li><li>同时从c排出血液进入外部血液容器颈动脉调节近端动脉压至80 mmHg。 </li><li>将动脉压监测系统连接到三通止动阀的剩余腔，并通过监测动脉压来控制排尿量。 </li><li>通过急性下降和远端动脉压力的持续丧失来确认主动脉闭塞的成功。 </li><li>主动脉闭塞9,10或11分钟后，放血Fogarty导管球囊，并重新灌注排出的血液。 </li></ol> 6.手术后护理和神经病学评估<ol><li>在通过尾动脉监测动脉压时，从股骨和颈动脉中取出导管，用丝线缝合闭合伤口。 </li><li>确认动脉压恢复到正常范围后，从尾动脉取出导管并闭合伤口。 </li><li>从麻醉恢复后，将大鼠回笼。 </li><li>评估你好在手术后24 h使用运动障碍指数（ 表1 ）检查肢体运动功能。运动赤字指数定义为步行分数与放置/步进反射分数之和。运动赤字指数为6表示最大赤字。 </li></ol> 7.组织病理学评估<ol><li>神经学评估后，用面罩递送的异氟烷麻醉大鼠，在麻醉下用100mL肝素化盐水经血流灌注处死，抽取脊髓。 8 </li><li>将来自腰椎3-5级的绳索部分嵌入石蜡中。 </li><li>用苏木精和伊红（H＆E）染色横断面。 </li><li>在显微镜下观察运动神经元损伤。 9 </li></ol> 8.统计分析<ol><li>使用统计软件包进行社会科学版20的统计分析使用Kruskal-Wallis检验比较三组的icit指数，其次是Mann-Whitney U检验。 P值&lt;0.05被认为具有统计学意义。 </li></ol>

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作者没有竞争的经济利益。这项工作得到韩国政府国家研究基金会拨款2012R1A1A3014010的支持。

在目前的研究中，我们展示了一种基于Taira和Marsala方法5的脊髓缺血大鼠模型，其根据主动脉闭塞时间在后肢中引起不同程度的运动障碍。 主动脉闭塞的长度可影响运动障碍的程度。如果主动脉闭塞时间较长，运动缺陷变得更加严重。因此，研究人员可以通过控制该模型中的主动脉闭塞时间来实现一定程度的运动障碍。 我们的模型涉及?...

截瘫是胸腹主动脉瘤手术的致命并发症。这是由于在主动脉夹紧和松开过程中发生的脊髓缺血 - 再灌注损伤。 1个几种策略包括全身体温过低和脑脊液引流已被引入到保护脊髓，2，3，4，但许多患者仍然受到伤病影响。 引入了几种动物脊髓缺血模型来研究其发病机制，制定了对损伤的保护策略。在本研究中，我们概述了基于Taira和Marsala方法的脊髓缺血大鼠模型。 5大鼠的脊髓循环系统与人类脊髓血管和侧支系统非常相似，尽管大小和位置。 6,7因此，大鼠是解剖学上合适的动物，以利用用于实验模型调查发病，并发症和治疗脊髓缺血的。此外，这种脊髓缺血模型通过利用胸主动脉的血管内气囊闭塞以最小的干预产生可靠的主动脉闭塞。 在这项研究中，我们证明，这种脊髓缺血大鼠模型诱导后肢的可重复的运动缺陷，其严重程度随主动脉闭塞时间而变化。

<table><tbody><tr><td>Fogarty Arterial Embolectomy catheter</td><td>Edward Life Sciences</td><td>120602F</td><td>a balloon-tipped catheter inserted into the femoral artery</td></tr><tr><td>BD Insyte-N Autoguard Shielded IV catheter&amp;nbsp;</td><td>BD&amp;nbsp;</td><td>381411</td><td>24-gauge intravenous catheter</td></tr><tr><td>50 mL syringe</td><td>KOREA VACCINE&amp;nbsp;</td><td>KOVAX-SYRINGE 50mL</td><td>Facial mask</td></tr><tr><td>1 mL syringe</td><td>KOREA VACCINE</td><td>KOVAX-SYRINGE 1ml</td><td></td></tr><tr><td>Recal probe</td><td>HARVARD APPARATUS</td><td>50-7221F</td><td>Rectal probe for temperature monitoring</td></tr><tr><td>Micro dissecting spring scissor</td><td>Jeung do bio &amp;amp; Plant co.LTD.</td><td>JD-S-10</td><td>Micro-scissor</td></tr><tr><td>SCISSOR (SHARP-SHARP)</td><td>Jeung do bio &amp;amp; Plant co.LTD.</td><td>S-51-12-S</td><td>Scissors</td></tr><tr><td>Retractor</td><td>Jeung do bio &amp;amp; Plant co.LTD.</td><td>JD-S-74A</td><td>Retractor</td></tr><tr><td>Micro forcep&amp;nbsp;</td><td>Jeung do bio &amp;amp; Plant co.LTD.</td><td>JD-S-29</td><td>Micro-forceps</td></tr><tr><td>MOSQUITO FORCEP (Curved)</td><td>Jeung do bio &amp;amp; Plant co.LTD.</td><td>S-44-CPK</td><td>Curved forceps</td></tr><tr><td>DRESSING FORCEP&amp;nbsp;</td><td>Jeung do bio &amp;amp; Plant co.LTD.</td><td>S-37-16S</td><td>Blunted forceps</td></tr><tr><td>4/0 black silk&amp;nbsp;</td><td>Woori Medical</td><td>S431</td><td>4.0 black silk suture</td></tr><tr><td>3-WAY STOCK</td><td>Seonwon Medcal</td><td>D-98-01</td><td>3-way stopcock</td></tr><tr><td>Patient monitor</td><td>PHILIPS</td><td>MP20</td><td>The arterial pressure monitoring device.&amp;nbsp;</td></tr><tr><td>Heating blanket</td><td>Self production</td><td></td><td>Heating blanket</td></tr><tr><td>Microtube and external reservoir</td><td>Self production</td><td></td><td>Microtube and external reservoir</td></tr><tr><td>Heparin</td><td>JW Pharmaceutical</td><td></td><td>Heparin</td></tr><tr><td>0.9% NS 1000ml</td><td>JW Pharmaceutical</td><td></td><td>Normal saline</td></tr><tr><td>Isoflurane</td><td>Hana Med</td><td></td><td>Isoflurane</td></tr></tbody></table>

reproducible motor deficit following aortic occlusion in a rat model of spinal cord ischemia

<html>脊髓缺血是胸腹主动脉瘤手术后的致命并发症。研究人员可以使用脊髓缺血实验模型调查预防和治疗这种并发症的策略。这里描述的模型表明与大鼠脊髓缺血模型中胸主动脉闭塞后的闭塞长度有关的不同程度的截瘫。 2-Fr。气球导管通过股动脉进入下行胸主动脉，直到导管尖端置于麻醉的雄性Sprague-Dawley大鼠的左锁骨下动脉中。通过使导管气囊膨胀来诱导脊髓缺血。经过一段闭塞时间（9,10或11分钟）后，气囊放气。术后24 h采用运动缺陷指数进行神经病理学评估，收集脊髓进行组织病理学检查。 主动脉闭塞9分钟的大鼠在后肢显示出轻度且可逆的运动障碍，经受10分钟主动脉闭塞的大鼠出现中度但可逆运动障碍，经受主动脉闭塞11分钟的大鼠显示完全和持续瘫痪，大鼠主动脉闭塞持续时间较长的大鼠脊髓部分运动神经元更保守。 使用这种脊髓缺血模型，研究人员可以在胸主动脉闭塞后达到可重现的后肢运动障碍。

在脊髓缺血期间，主动脉闭塞9分钟（n = 3），10分钟（n = 3）或11分钟（n = 3）。大鼠的运动缺陷指数见表2.主动脉闭塞9分钟的大鼠在后肢显示轻度和可逆的运动障碍。大鼠经历10分钟的主动脉闭塞呈现中度运动缺陷，但不完全麻痹。经历11分钟闭塞时间的大鼠显示完全和持续性麻痹。 用H＆E染色的脊髓切片的代表性照片如图1所示。在经历较短持续时间的?...

Watch this Scientific Journal Video about Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia at JoVE.com

Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia

本研究显示了在大鼠中进行脊髓缺血的微创和易复制模型的技术。通过控制主动脉闭塞时间可以产生不同程度的后肢运动障碍。

主动脉阻塞后脊髓缺血大鼠模型中的可再生电机缺陷

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing ...

reproducible-motor-deficit-following-aortic-occlusion-rat-model

Research

JoVE Journal

Medicine

7.1K 次观看.  SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul. 本研究显示了在大鼠中进行脊髓缺血的微创和易复制模型的技术。通过控制主动脉闭塞时间可以产生不同程度的后肢运动障碍。 

视频: Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia

Focal Cerebral Ischemia Model by Endovascular Suture Occlusion of the Middle Cerebral Artery in the Rat

Stroke is the leading cause of disability and the third leading cause of death in adults worldwide1. 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 humans2,3. 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. Because recanalization commonly occurs following an acute stroke in the human, reperfusion after a period of occlusion has been included in many of these models. In this video, we demonstrate the transient endovascular suture MCAO model in the spontaneously hypertensive rat (SHR). A filament with a silicon tip coating is placed intraluminally at the MCA origin for 60 minutes, followed by reperfusion. Note that the optimal occlusion period may vary in other rat strains, such as Wistar or Sprague-Dawley. Several behavioral indicators of stroke in the rat are shown. Focal ischemia is confirmed using T2-weighted magnetic resonance images and by staining brain sections with 2,3,5-triphenyltetrazolium chloride (TTC) 24 hours after MCAO.

Surgical induction of ischemic brain damage in the rat is a widely used model for stroke research. Here we demonstrate the induction of focal cerebral ischemia by occlusion of the middle cerebral artery. Visualization of the resulting infarct by histological staining and magnetic resonance imaging is also shown.

焦距脑缺血模型大鼠大脑中动脉的血管内缝合闭塞

Stroke is the leading cause of disability and the third leading cause of death in adults worldwide1. In human stroke, there exists a highly variable ...

科研

神经科学

2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia

Cardiac arrest followed by resuscitation often results in dramatic brain damage caused by ischemia and subsequent reperfusion of the brain. Global brain ischemia produces damage to specific brain regions shown to be highly sensitive to ischemia 1. Hippocampal neurons have higher sensitivity to ischemic insults compared to other cell populations, and specifically, the CA1 region of the hippocampus is particularly vulnerable to ischemia/reperfusion 2.
The design of therapeutic interventions, or study of mechanisms involved in cerebral damage, requires a model that produces damage similar to the clinical condition and in a reproducible manner. Bilateral carotid vessel occlusion with hypotension (2VOH) is a model that produces reversible forebrain ischemia, emulating the cerebral events that can occur during cardiac arrest and resuscitation. We describe a model modified from Smith et al. (1984) 2, as first presented in its current form in Sanderson, et al. (2008) 3, which produces reproducible injury to selectively vulnerable brain regions 3-6. The reliability of this model is dictated by precise control of systemic blood pressure during applied hypotension, the duration of ischemia, close temperature control, a specific anesthesia regimen, and diligent post-operative care. An 8-minute ischemic insult produces cell death of CA1 hippocampal neurons that progresses over the course of 6 to 24 hr of reperfusion, while less vulnerable brain regions are spared. This progressive cell death is easily quantified after 7-14 days of reperfusion, as a near complete loss of CA1 neurons is evident at this time.
In addition to this brain injury model, we present a method for CA1 damage quantification using a simple, yet thorough, methodology. Importantly, quantification can be accomplished using a simple camera-mounted microscope, and a free ImageJ (NIH) software plugin, obviating the need for cost-prohibitive stereology software programs and a motorized microscopic stage for damage assessment.

Bilateral carotid occlusion coupled with systemic hypotension produces global brain ischemia in the rat, resulting in damage to the hippocampus with reproducible severity. Animal subjects are impaired with predictable patterns of brain damage, they recover expediently, and mortality rates are comparatively low.

2血管闭塞/低血压：全脑缺血模型大鼠

Cardiac arrest followed by resuscitation often results in dramatic brain damage caused by ischemia and subsequent reperfusion of the brain. Global brain ...

医学

Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion

Background 
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury.&#160;The current model demonstrates reproducible lower&#160;extremity paralysis following thoracic aortic occlusion.
Methods 
Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery.&#160; Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr.
Results 
Mice that underwent sham surgery showed no observable hind&#160;limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post&#160;operative mortality.
Conclusion 
Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.

The lack of mechanistic understanding of spinal cord ischemia-reperfusion injury has hindered further adjuncts to prevent paraplegia following high risk aortic operations. Thus, the development of animal models is imperative. This manuscript demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion in a murine model.

可重放截瘫胸主动脉阻断脊髓缺血再灌注的小鼠模型

Background
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered ...

Performing Permanent Distal Middle Cerebral with Common Carotid Artery Occlusion in Aged Rats to Study Cortical Ischemia with Sustained Disability

Stroke typically occurs in elderly people with a range of comorbidities including carotid (or other arterial) atherosclerosis, high blood pressure, obesity and diabetes. Accordingly, when evaluating therapies for stroke in animals, it is important to select a model with excellent face validity. Ischemic stroke accounts for 80% of all strokes, and the majority of these occur in the territory of the middle cerebral artery (MCA), often inducing infarcts that affect the sensorimotor cortex, causing persistent plegia or paresis on the contralateral side of the body. We demonstrate in this video a method for producing ischemic stroke in elderly rats, which causes sustained sensorimotor disability and substantial cortical infarcts. Specifically, we induce permanent distal middle cerebral artery occlusion (MCAO) in elderly female rats by using diathermy forceps to occlude a short segment of this artery. The carotid artery on the ipsilateral side to the lesion was then permanently occluded and the contralateral carotid artery was transiently occluded for 60 min. We measure the infarct size using structural T2-weighted magnetic resonance imaging (MRI) at 24 hr and 8 weeks after stroke. In this study, the mean infarct volume was 4.5% &#177; 2.0% (standard deviation) of the ipsilateral hemisphere at 24 hr (corrected for brain swelling using Gerriet&#8217;s equation, n = 5). This model is feasible and clinically relevant as it permits the induction of sustained sensorimotor deficits, which is important for the elucidation of pathophysiological mechanisms and novel treatments.

Here we present a protocol to produce permanent distal middle cerebral artery occlusion in elderly female rats with simultaneous occlusion of the carotid arteries to generate large cortical infarcts and sustained deficits. We show confirmation of the lesion size using structural MRI at 24 hr and 8 weeks after stroke.

执行永久远端大脑中与老年大鼠颈总动脉闭塞研究皮层缺血具有持续残疾

Stroke typically occurs in elderly people with a range of comorbidities including carotid (or other arterial) atherosclerosis, high blood pressure, ...

Modeling Stroke in Mice: Transient Middle Cerebral Artery Occlusion via the External Carotid Artery

Stroke is the third most common cause of mortality and the leading cause of acquired adult disability in developed countries. To date, therapeutic options are limited to a small proportion of stroke patients within the first hours after stroke. Novel therapeutic strategies are being extensively investigated, especially to prolong the therapeutic time window. These current investigations include the study of important pathophysiological pathways after stroke, such as post-stroke inflammation, angiogenesis, neuronal plasticity, and regeneration. Over the last decade, there has been increasing concern about the poor reproducibility of experimental results and scientific findings among independent research groups. To overcome the so-called &#8220;replication crisis&#8221;, detailed standardized models for all procedures are urgently needed. As an effort within the &#8220;ImmunoStroke&#8221; research consortium (https://immunostroke.de/), a standardized mouse model of transient middle cerebral artery occlusion (MCAo) is proposed. This model allows the complete restoration of the blood flow upon removal of the filament, simulating the therapeutic or spontaneous clot lysis that occurs in a large proportion of human strokes. The surgical procedure of this &#8220;filament&#8221; stroke model and tools for its functional analysis are demonstrated in the accompanying video.

Different models of middle cerebral artery occlusion (MCAo) are used in experimental stroke research. Here, an experimental stroke model of transient MCAo via the external carotid artery (ECA) is described, which aims to mimic human stroke, in which the cerebrovascular thrombus is removed due to spontaneous clot lysis or therapy.

模拟小鼠中风:通过颈外动脉的短暂性脑中动脉闭塞

Stroke is the third most common cause of mortality and the leading cause of acquired adult disability in developed countries. To date, therapeutic options ...

Real-Time Assessment of Spinal Cord Microperfusion in a Porcine Model of Ischemia/Reperfusion

Spinal cord injury is a devastating complication of aortic repair. Despite developments for the prevention and treatment of spinal cord injury, its incidence is still considerably high and therefore, influences patient outcome. Microcirculation plays a key role in tissue perfusion and oxygen supply and is often dissociated from macrohemodynamics. Thus, direct evaluation of spinal cord microcirculation is essential for the development of microcirculation-targeted therapies and the evaluation of existing approaches in regard to spinal cord microcirculation. However, most of the methods do not provide real-time assessment of spinal cord microcirculation. The aim of this study is to describe a standardized protocol for real-time spinal cord microcirculatory evaluation using laser-Doppler needle probes directly inserted in the spinal cord. We used a porcine model of ischemia/reperfusion to induce deterioration of the spinal cord microcirculation. In addition, a fluorescent microsphere injection technique was used. Initially, animals were anesthetized and mechanically ventilated. Thereafter, laser-Doppler needle probe insertion was performed, followed by the placement of cerebrospinal fluid drainage. A median sternotomy was performed for exposure of the descending aorta to perform aortic cross-clamping. Ischemia/reperfusion was induced by supra-celiac aortic cross-clamping for a total of 48 min, followed by reperfusion and hemodynamic stabilization. Laser-Doppler Flux was performed in parallel with macrohemodynamic evaluation. In addition, automated cerebrospinal fluid drainage was used to maintain a stable cerebrospinal pressure. After completion of the protocol, animals were sacrificed, and the spinal cord was harvested for histopathological and microsphere analysis. The protocol reveals the feasibility of spinal cord microperfusion measurements using laser-Doppler probes and shows a marked decrease during ischemia as well as recovery after reperfusion. Results showed comparable behavior to fluorescent microsphere evaluation. In conclusion, this new protocol might provide a useful large animal model for future studies using real-time spinal cord microperfusion assessment in ischemia/reperfusion conditions.

Spinal cord microcirculation plays a pivotal role in spinal cord injury. Most methods do not allow real-time assessment of spinal cord microcirculation, which is essential for the development of microcirculation-targeted therapies. Here, we propose a protocol using Laser-Doppler-Flow Needle probes in a large animal model of ischemia/reperfusion.

猪缺血/再灌注模型中脊髓微灌注的实时评估

Spinal cord injury is a devastating complication of aortic repair. Despite developments for the prevention and treatment of spinal cord injury, its ...

Real-Time Monitoring and Modulation of Blood Pressure in a Rabbit Model of Ischemic Stroke

Control of blood pressure, in terms of both absolute values and its variability, affects outcomes in ischemic stroke patients. However, it remains challenging to identify the mechanisms that lead to poor outcomes or evaluate measures by which these effects can be mitigated because of the prohibitive limitations inherent to human data. In such cases, animal models can be utilized to conduct rigorous and reproducible evaluations of diseases. Here we report refinement of a previously described model of ischemic stroke in rabbits that is augmented with continuous blood pressure recording to assess the impacts of modulation on blood pressure. Under general anesthesia, femoral arteries are exposed through surgical cutdowns to place arterial sheaths bilaterally. Under fluoroscopic visualization and roadmap guidance, a microcatheter is advanced into an artery of the posterior circulation of the brain. An angiogram is performed by injecting the contralateral vertebral artery to confirm occlusion of the target artery. With the occlusive catheter remaining in position for a fixed duration, blood pressure is continuously recorded to allow for tight titration of blood pressure manipulations, whether through mechanical or pharmacological means. At the completion of the occlusion interval, the microcatheter is removed, and the animal is maintained under general anesthesia for a prescribed length of reperfusion. For acute studies, the animal is then euthanized and decapitated. The brain is harvested and processed to measure the infarct volume under light microscopy and further assessed with various histopathological stains or spatial transcriptomic analysis. This protocol provides a reproducible model that can be utilized for more thorough preclinical studies on the effects of blood pressure parameters during ischemic stroke. It also facilitates effective preclinical evaluation of novel neuroprotective interventions that might improve care for ischemic stroke patients.

Continuous arterial blood pressure recording allows the investigation of impacts of various hemodynamic parameters. This report demonstrates the application of continuous arterial blood pressure monitoring in a large animal model of ischemic stroke for determination of stroke pathophysiology, impact of different hemodynamic factors, and the assessment of novel treatment approaches.

缺血性脑卒中兔模型中血压的实时监测和调节

Control of blood pressure, in terms of both absolute values and its variability, affects outcomes in ischemic stroke patients. However, it remains ...

Middle Cerebral Artery Occlusion in Rats with Preserved Vascular Anatomy

A Rat Model of Middle Cerebral Artery Occlusion/Reperfusion Without Damaging the Anatomical Structure of Cerebral Vessels

Ischemic stroke stands as the primary cause of long-term disability and mortality among adults worldwide. Animal models of ischemic stroke have significantly contributed to our understanding of its pathological mechanisms and the development of potential treatments. Presently, there are two common methods involving filament (endovascular suture) techniques to induce animal models of cerebral ischemia. However, these methods have inherent limitations, such as reduced blood perfusion to the brain, damage to the external carotid artery system, impaired food and/or water intake, and sensory dysfunction of the face. This article introduces a new method for inducing a rat ischemic stroke model without compromising the cerebral vascular anatomy. In this study, the common carotid artery (CCA) of Sprague-Dawley rats was exposed, and an incision was made. A filament was then inserted through the incision into the internal carotid artery to occlude the middle cerebral artery. After 1.5 h of induced ischemia, the occluding filament was fully removed from both the internal carotid artery and the CCA. The incision in the CCA was subsequently sutured using 11-0 microsurgical sutures under a microscope (magnification 4x). Through the utilization of microsurgical techniques to repair the CCA, this study successfully developed a unique method to induce an ischemic stroke model in rats while preserving the anatomical integrity of cerebral blood vessels.

The current protocol describes a rat model of middle cerebral artery occlusion/reperfusion that preserves the anatomical structure of cerebral vessels without causing damage.

Ischemic stroke stands as the primary cause of long-term disability and mortality among adults worldwide. Animal models of ischemic stroke have ...

<meta charset="utf8"></head><body>免疫荧光染色研究大鼠 MCAO 卒中模型中的细胞死亡

Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke

Stroke is a leading cause of death and disability worldwide. Most cases of stroke are ischemic and result from the occlusion of the middle cerebral artery (MCA). Current pharmacological approaches for the treatment of ischemic stroke are limited; therefore, novel therapies providing effective neuroprotection against ischemic injury following stroke are urgently needed. In the brain tissue following ischemic stroke, the area of the ischemic penumbra is salvageable but at risk of progressing to irreversible damage. The penumbral area surrounding the infarcted core is a conceptual target for neuroprotection. Since the blood flow is partially maintained in the penumbral area, neuronal and non-neuronal cells in this area transiently survive after stroke, and these cells that are still viable may be rescued by appropriate medical interventions. Understanding the pathophysiology of the penumbra is important in the development of neuroprotective therapies because the cell death pathways activated in the ischemic penumbra may indicate therapeutic targets, such as RUNX1 and cathepsins. These protein targets functioning as mediators of programmed cell death can be further exploited in translational research. With moderate size and similarity to the human brain, the in vivo rat model of MCA occlusion (MCAO) mimics the human ischemic stroke and offers an applicable tool to investigate the penumbral pathology, examine the cell death signaling, and evaluate the effects of potential targets in the context of MCAO. Here, we describe how to induce MCAO in rats and how to perform immunofluorescence staining for the detection of cell death signaling in the rat brain following MCAO.

<meta charset="utf8"></head><body>通过免疫荧光评估缺血性卒中大鼠模型中的细胞死亡信号

Rat in vivo models are indispensable tools to investigate the pathological mechanisms and therapeutic targets for ischemic stroke. This work will describe performing immunofluorescence staining in infarcted brain slices following middle cerebral artery occlusion (MCAO) in rats.

通过免疫荧光评估缺血性卒中大鼠模型中的细胞死亡信号

Stroke is a leading cause of death and disability worldwide. Most cases of stroke are ischemic and result from the occlusion of the middle cerebral artery ...

主动脉阻塞后脊髓缺血大鼠模型中的可再生电机缺陷

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此视频中的章节

焦距脑缺血模型大鼠大脑中动脉的血管内缝合闭塞

2血管闭塞/低血压：全脑缺血模型大鼠

可重放截瘫胸主动脉阻断脊髓缺血再灌注的小鼠模型

执行永久远端大脑中与老年大鼠颈总动脉闭塞研究皮层缺血具有持续残疾

模拟小鼠中风:通过颈外动脉的短暂性脑中动脉闭塞

猪缺血/再灌注模型中脊髓微灌注的实时评估

缺血性脑卒中兔模型中血压的实时监测和调节

A Rat Model of Middle Cerebral Artery Occlusion/Reperfusion Without Damaging the Anatomical Structure of Cerebral Vessels

通过免疫荧光评估缺血性卒中大鼠模型中的细胞死亡信号

通过免疫荧光评估缺血性卒中大鼠模型中的细胞死亡信号