Name: rat model of blood-brain barrier disruption to allow targeted neurovascular therapeutics
Uploaded: 2012-11-30T12:00:00
Description: Watch this Scientific Journal Video about Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics at JoVE.com

这项工作是支持的JB马歇尔基金会。

1。准备过程的动物和设备<ol><li>手术开始之前，准备手术区和动物。使颈动脉导管插入到一端12“PE50管23隔距的钝针剪切在导管的另一端的约45°的斜角。消毒设备之前的程序。戴上头发阀盖，外科口罩和无菌手套。 </li><li>表面上放置一个加热垫，手术将进行。激活它，让它温暖。覆盖的区域的吸收性板凳垫。 </li><li>请确认你有25％甘露醇溶液中无晶体。如果晶体存在，溶解由小瓶放置在80℃的?...

<ol>
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A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+drug+delivery+to+intracerebral+tumor+and+surrounding+brain+in+a+rodent+model:+a+comparison+of+osmotic+versus+bradykinin+modification+of+the+blood-brain+and/or+blood-tumor+barriers.">Improving drug delivery to intracerebral tumor and surrounding brain in a rodent model: a comparison of osmotic versus bradykinin modification of the blood-brain and/or blood-tumor barriers.</a> Neurosurgery. 43, 879 (1998).</li><li>Kinoshita, M., McDannold, N., Jolesz, F. 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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemotherapy+administered+in+conjunction+with+osmotic+blood-brain+barrier+modification+in+patients+with+brain+metastases.">Chemotherapy administered in conjunction with osmotic blood-brain barrier modification in patients with brain metastases.</a> Journal of neuro-oncology. 4, 195-207 (1987).</li><li>Doolittle, N. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+and+efficacy+of+a+multicenter+study+using+intraarterial+chemotherapy+in+conjunction+with+osmotic+opening+of+the+blood-brain+barrier+for+the+treatment+of+patients+with+malignant+brain+tumors.">Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors.</a> Cancer. 88, 637-647 (2000).</li><li>Guillaume, D. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intra-arterial+chemotherapy+with+osmotic+blood-brain+barrier+disruption+for+aggressive+oligodendroglial+tumors:+results+of+a+phase+I+study.">Intra-arterial chemotherapy with osmotic blood-brain barrier disruption for aggressive oligodendroglial tumors: results of a phase I study.</a> Neurosurgery. 66, 48 (2010).</li><li>Remsen, L. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+influence+of+anesthetic+choice,+PaCO2,+and+other+factors+on+osmotic+blood-brain+barrier+disruption+in+rats+with+brain+tumor+xenografts.">The influence of anesthetic choice, PaCO2, and other factors on osmotic blood-brain barrier disruption in rats with brain tumor xenografts.</a> Anesthesia &amp; Analgesia. 88, 559-559 (1999).</li><li>Nilaver, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Delivery+of+herpesvirus+and+adenovirus+to+nude+rat+intracerebral+tumors+after+osmotic+blood-brain+barrier+disruption.">Delivery of herpesvirus and adenovirus to nude rat intracerebral tumors after osmotic blood-brain barrier disruption.</a> Proceedings of the National Academy of Sciences. 92, 9829 (1995).</li><li>Fortin, D., McCormick, C. I., Remsen, L. G., Nixon, R., Neuwelt, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Unexpected+neurotoxicity+of+etoposide+phosphate+administered+in+combination+with+other+chemotherapeutic+agents+after+blood-brain+barrier+modification+to+enhance+delivery,+using+propofol+for+general+anesthesia,+in+a+rat+model.">Unexpected neurotoxicity of etoposide phosphate administered in combination with other chemotherapeutic agents after blood-brain barrier modification to enhance delivery, using propofol for general anesthesia, in a rat model.</a> Neurosurgery. 47, 199 (2000).</li><li>Neuwelt, E. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Primary+CNS+lymphoma+treated+with+osmotic+blood-brain+barrier+disruption:+prolonged+survival+and+preservation+of+cognitive+function.">Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function.</a> Journal of clinical oncology. 9, 1580 (1991).</li><li>Remsen, L. G., Trail, P. A., Hellstr&#246;m, I., Hellstr&#246;m, K. E., Neuwelt, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enhanced+delivery+improves+the+efficacy+of+a+tumor-specific+doxorubicin+immunoconjugate+in+a+human+brain+tumor+xenograft+model.">Enhanced delivery improves the efficacy of a tumor-specific doxorubicin immunoconjugate in a human brain tumor xenograft model.</a> Neurosurgery. 46, 704 (2000).</li><li>Neuwelt, E. A., Pagel, M. A., Kraemer, D. F., Peterson, D. R., Muldoon, L. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bone+marrow+chemoprotection+without+compromise+of+chemotherapy+efficacy+in+a+rat+brain+tumor+model.">Bone marrow chemoprotection without compromise of chemotherapy efficacy in a rat brain tumor model.</a> Journal of Pharmacology and Experimental Therapeutics. 309, 594-599 (2004).</li></ol>

有几个的最大化疗效BBBD的装置。这是重要的，以尽量减少在切口向下阶段出血。血压和心脏速率可以由大出血的影响，这些因素已知影响程度BBBD 13的 。出血可减少通过使用缝合线结扎大血管，如甲状腺上和枕动脉，必须除以。此外，电，可以用来划分的血管和剖析领域有丰富的血液供应。同样重要的是，以保持空气和固体放入动物的所有行，满分 - 尤其是颈动脉导管。与甘露醇快速工?...

<table border="1"><tbody><tr><td> 材料名称 </td><td> 公司 </td><td> 目录编号 </td><td> 评论 </td></tr><tr><td>只Long Evans鼠</td><td>哈伦实验室</td><td></td><td> 210-250克，男</td></tr><tr><td> PE 50管</td><td> Beckton - 迪金森</td><td></td><td></td></tr><tr><td> 18号×2.5“静脉导管</td><td>泰尔茂</td><td></td><td>对于ET管</td></tr><tr><td> 30“四分机设定</td><td>雅培</td><td></td><td></td></tr><tr><td> 26号兽医静脉导管</td><td> Monoject </td><td></td><td></td></tr><tr><td>伊文思蓝染料</td><td>西格玛</td><td> E2129 </td><td></td></tr><tr><td>双极性</td><td>科德曼</td><td></td><td></td></tr><tr><td> 5微米过滤器， </td><td>布劳恩</td><td></td><td></td></tr></tbody></table>

rat model of blood-brain barrier disruption to allow targeted neurovascular therapeutics

紧密连接的内皮细胞与基底膜和星形胶质细胞末端的脚环绕脑血管的形成血-脑屏障。选择性的阻挡排除分子根据它们的大小和电荷的血液和脑之间交叉。此功能可以阻碍治疗神经系统疾病的交付。化疗药物的一些，例如，将不会有效地穿过血-脑屏障到达肿瘤细胞2。因此，改善药物透过血 - 脑屏障的交付是感兴趣的区域。 为提高药物的交付到大脑的最普遍的方法是直接脑输注和血-脑屏障破坏3。直接脑内输液保证疗法到达大脑，然而，这种方法具有的能力是有限的药物分散4。血 - 脑屏障的中断（BBBD）人低点流直接从循环系统的药物 到大脑，从而更有效地达到分散的肿瘤细胞。三种方法的屏障破坏，渗透屏障破坏，药物屏障破坏，聚焦超声微泡。渗透破坏，开创Neuwelt，使用高渗溶液，25％甘露醇脱水的细胞血 - 脑屏障，使他们萎缩，瓦解他们的紧密连接。屏障破坏，也可以完成药理上具有血管活性化合物5，如组胺，缓激肽6。然而，该方法中，是有选择性的，主要用于脑肿瘤屏障7。此外，RMP-7，血管舒缓激肽的肽的类似物，被发现时相比，头-对-头与渗透BBBD与25％甘露糖醇8差。聚焦超声（FUS）与微泡的超声造影剂的结合，另一种方法，也被证明可逆打开的血-脑屏障。在比较FUS，不过，25％甘露醇有一个较长的历史，在人类患者中的安全性，它使一个行之有效的工具转化研究10-12。 为了实现BBBD，甘露糖醇，必须以很高的速率直接进入大脑的动脉循环交付。在人类中，血管内导管被引导到大脑，其中可以实现快速，直接流。 “本协议模型人BBBD尽可能接近。经过切口下降到常见的颈动脉分叉处，导管插入逆行进入ECA和用于提供甘露糖醇直接到内颈动脉（ICA）的循环。丙泊酚和N 2 O麻醉用于自己的能力发挥最大的效益屏障破坏13。如果执行得当，此过程有安全，有效，可逆打开血 - 脑屏障和即兴表演的能力e的药物，通常不会到达大脑8,13,14交付。

<img alt="图1" src="/files/ftp_upload/50019/50019fig1.jpg" /> 图1。可视化通过血-脑屏障破坏Evans蓝染料外渗。Evans蓝染料是与白蛋白结合，未外渗进入大脑在生理条件下的颜料。血 - 脑屏障的大脑的一侧上的中断允许Evans蓝进入和染色的打乱的半球的蓝色，而在非破坏的半球不变。因此，这是一个有用的标记血-脑屏障破坏， 图1A是一个示例的脑无血-脑...

Watch this Scientific Journal Video about Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics at JoVE.com

Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics

血 - 脑屏障破坏，帮助某些药物输送到大脑。甘露醇动脉内交付收缩血管周围的细胞，以扰乱障碍。

允许有针对性的大鼠模型血 - 脑屏障破坏神经血管治疗

Endothelial cells with tight junctions along with the basement membrane and astrocyte end feet surround cerebral blood vessels to form the blood-brain ...

Research

JoVE Journal

Medicine

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model

MRI引导下的破坏血脑屏障在大鼠模型经颅聚焦超声

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a ...

科研

医学

Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

Stretch in Brain Microvascular Endothelial Cells cEND as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

作为脑微血管内皮细胞（CEND）的伸展<em&gt;体外</em创伤性脑损伤模型血脑屏障

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying ...

Setting-up an In Vitro Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport

Setting-up an In Vitro Model of Rat Blood-brain Barrier BBB: A Focus on BBB Impermeability and Receptor-mediated Transport

设置了一个<em&gt;体外</em大鼠血脑屏障&gt;模型（BBB）：在BBB抗渗性和受体介导的运输为中心

The blood brain barrier (BBB) specifically regulates molecular and cellular flux between the blood and the nervous tissue. Our aim was to develop and ...

Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction

Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction

缺氧缺糖再给氧作为<em&gt;在体外</em&gt;缺血再灌注损伤模型的研究血脑屏障功能障碍

Ischemia-Reperfusion (IR) injury is known to contribute significantly to the morbidity and mortality associated with ischemic strokes. Ischemic ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

大鼠颈动脉球囊损伤模型试验抗血管重建治疗

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction

Retroductal颌下腺灌输和本地化分割照射在涎腺功能减退症大鼠模型

Normal tissues that lie within the portals of radiation are inadvertently damaged. Salivary glands are often injured during head and neck radiotherapy. ...

In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption

In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption

评估血脑屏障网状血管形成和破坏的体外测定

Blood-brain barrier (BBB) coverage plays a central role in the homeostasis of the central nervous system (CNS). The BBB is dynamically maintained by ...

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

一种基于猪脑内皮细胞的体外血脑屏障模型的改进方法

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

用线 Myography 测定小鼠肠系膜动脉的等轴收缩力

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model

猪心肌梗死模型中心脏活性疗法的递送

Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or ...