作者要感谢中心的分子和基因组成像加州大学戴维斯分校的生物医学成像部门在Genentech公司。这项工作是由卫生部生物工程研究合作伙伴的授权号R01 EB00993一个国家机构的支持。

所有的动物处理和程序本文所述，并根据动物研究：报告体内实验（到达）的指导方针，按照批准的协会为实验动物的评审评估方案进行（AAALAC）的国际认证机构动物护理和使用委员会在加州大学戴维斯分校。适当的手术不应导致的在动物的任何疼痛或不适的迹象，但如果这些标志观察到，包括的止痛剂或在某些情况下施用安乐死应采取适当的步骤。右侧的动物是任意选择为所描述的单方面过程。 1.单侧颈总动脉（CCA）结扎<ol><li>准备无菌区与定位方便消毒外科手术工具和材料。确保加热垫加热至37℃，温度探针牢固地放置在垫。 ＆＃160;一定要使用一个无菌的悬垂覆盖手术部位。 </li><li>麻醉动物（异氟烷，在空气中1-3％在0.5-1升/分钟），并将其放置在动物的尾背向仰卧位置。检查麻醉按捏脚趾 - 这应该引起任何反应，如果动物是正确麻醉。应用眼药膏的眼睛。 </li><li>申请脱毛霜下颈部使用1-2棉签上胸部区域。等待1-3分钟，然后用湿纱布或酒精棉签去除毛发和奶油。优碘擦拭切口面积以循环的方式从内到外，再换上无菌手术手套。 </li><li>用手术剪，使约1厘米的切口沿着下颈部的中线。小心地用手术剪周围筋膜分开外皮。 </li><li>使用两个麦弗逊式微虹膜缝合镊子，从筋膜分离右侧颈总动脉，注意避免破坏静脉或distur兵迷走神经。 </li><li>使用镊子在右边，exteriorize右侧CCA在稳定的位置。应用数滴盐水以防止干燥。通过右侧CCA下方6-0丝线缝合，结扎，并使用双平结合适的长度（2-3厘米）。任选，结扎用6-0丝线缝合一个第二长度一次。 </li><li>重新定位正确的CCA和使用无菌海绵打开清理多余的液体放倒棉签。关闭切口用6-0丝线缝合。应用利多卡因局部达7毫克/公斤。 </li><li>让动物从麻醉到门诊（约30分钟），回收并进行手术后的监控，直到动物准备成像。 </li></ol> 2.准备成像：系统和硬件检查<ol><li>设置硬件和软件的MRI和PET系统，并检查其功能如下。确保所有物理连接是否牢固和软件设置适当选择。 <ol><li&gt;确保在PET系统是在5℃下使用空气冷却系统的规定的工作温度。 </li><li>摩宠物系统的MRI孔内，对准了使用已知轴偏移视角（FOV）中心的PET和MRI领域。挂载MRI线圈宠物系统的孔内和中心线圈与PET系统和MRI磁体中心。 </li><li>打开PET电子电源和偏置电压（注：步将用乐器不同）。采用68缸戈执行快速（5分钟）的扫描和检查所生成的正弦图，以确保所有探测器的操作。 </li><li>任选获得用于用于共登记用途的PET / MRI变换矩阵数据：填充三维幻影（例如，三填充球）与200微居里的18 F-水溶液和获得15分钟的PET带。获取解剖MRI数据：在扫描控制窗口中，选择多片多回波（MSME）序列（ 见表 1 </strong&gt;的信息）。重复所有三个主要方向：轴向，矢状面和冠状。 </li></ol></li><li>检查输液泵的设置和操作。设置泵每分钟4.44微升，而在恒定输注45分钟提供200微升，对于静脉注射在20克的动物的典型建议的限制的总体积。 </li><li>检查加热器操作，并确认所述温度输出是足以保持动物温热（37℃）。检查温度和呼吸监测工作正常，准备对动物睡觉的动物安置。 </li><li>通过与压缩空气源关闭和 O 2 和 N 2在两个供电：检查O 2和N 2的流量计的操作（O 2在57.2毫克/分和 N 2在0.575克/分0.5升/分钟）来源上。为了避免损坏流量计的危险，不要打开它们没有足够的输入压力。 </li><li>确保异氟醚vaporizer被充分填充。在成像之前，启动异氟烷麻醉流量在1-2％和0.5至1升/分。 </li><li>制备动物床通过确保麻醉，呼吸垫，和加热器系统被安全地和功能性地定位。有关其他的PET /磁共振配准准确度，基准标记（例如，毛细管在相似浓度作为注射成像填充有放射性示踪剂）可以附着到动物床的视野内。 </li></ol> 3.成像工作流程毕竟必要的设备检查完成后，继续成像如下： <ol><li>麻醉用异氟烷的动物，并插入尾静脉导管（28克针，PE-10管小于5厘米）填充有肝素生理盐水（0.5毫升肝素，1000 USP /毫升，在10毫升盐水）。升温动物和/或尾可能提高的导管插入精度。任选放置一滴氰基丙烯酸酯类粘合剂的上插入部位以固定IV线。 </li><li>动物转移到准备好的动物床。确保动物的头是安全的，与上门牙的位置固定在牙齿的酒吧和耳棒，如果正在使用。 </li><li>应用眼药膏的眼睛，以防止干燥。插入直肠探头温度计。确保温度和呼吸读数功能。 </li><li>绘制示踪剂剂量（约600微居里在200μl）注射到肝素化的PE-10管的适当长度 - 约3μm对于PE-10管材和200微升的体积。连接该管道到输液泵的注射器，而另一对尾静脉导管线的一端，注意不要用来在管穿孔。 </li><li>向前滑动动物床到磁体的孔，确保不干扰磁共振线圈的定位和任何线路或电缆，尤其是麻醉管。保证大脑的中心与M的中心对准RI线圈，宠物系统，以及MRI磁体。 </li><li>通过旋转线圈上的调节旋钮，最小化阻抗（检查线圈规格）和频率（300兆赫1 H在7特斯拉的）不匹配，通过观察高功率前置放大器的显示执行调谐的MRI线圈的和匹配。 </li><li> （MRI）的调谐和匹配后，获取侦察图像：选择一种罕见的tripilot序列和运行扫描控制窗口的顺序。检查动物的定位，重复步骤3.5，并根据需要3.6。重置垫片到零值。 </li><li> （MRI）取得局部，点分辨光谱扫描（PRESS）的体积在大脑中：运行PRESS序列（ 见表 1）在一个长方体，尺寸为3.9毫米×6毫米×9毫米。检查水线宽使用CalcLineWidth宏命令。如果在一半最大值（FWHM）值全宽是可以接受的（例如，为0.2ppm），继续到步骤3.10。如果没有，继续执行步骤3。9。 </li><li> （MRI）获取字段映射：运行FieldMap序列（ 见表 1）。通过运行MAPSHIM宏命令，并选择线性和二阶（Z 2）局部调整，使用了多角度的投影垫片（MAPSHIM）产生的数据。重复步骤3.8。 </li><li> （MRI）位置的DWI扫描（ 见表 1）切片的计划：使用几何编辑器，确保收购FOV定位获取的大脑内的利益所需的音量。如果得到的片计划是一致的需要，复制在扫描控制窗口此片计划，所有后续弥散加权成像扫描。开始采集。 </li><li> （PET）随着PET收购准备，并准备开始，启动输液泵。预先确定的延迟，其中从导管盐水已经注入之后，开始以捕获放射性示踪剂的条目的PET收集（ 见表 1）。监控计数率并查找逐渐增加在表明一个成功的注射次数。 </li><li>后10-15分钟，引发缺氧的挑战并行执行步骤3.12。以引发缺氧挑战，关掉医用空气流，并立即功率上的 O 2 和 N 2的流量计与预定的设置来提供8％的氧气和92％的氮气，并减少异氟烷〜0.8％。 请在流量计不功率而不输入压力。 </li><li> （MRI）的同时作为步骤3.12，开始在步骤3.10制备DWI采集（扫描“H1”）。 </li><li> （MRI）的开始DWI采集（扫描“H2”），在步骤3.10制备后立即扫描H1被完成。通过关闭流量计，恢复医用空气流动，异氟醚浓度恢复到基于生理监测一个合适的值完缺氧的挑战。 </li><li> （MRI）收购后缺氧DWI扫描步骤3.10准备。关掉输液泵之后该扫描已完成。 </li><li> （MRI）取得ANATomical图像在轴向平面和径向平面。在扫描控制窗口-选择MSME序列（ 见表 1）。利用几何编辑器，确保收购FOV涵盖了大脑。 </li><li>除去动物，返回到笼卧床时 ​​监测和发病率的迹象，安乐死必要时用CO 2的施用颈椎脱位作为次要方法。 </li></ol>

<ol>
	<li>Donnan, G. 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=.">.</a> The Lancet. 371, 1614-1623 (2008).</li><li>Turner, R. C., 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+science+of+cerebral+ischemia+and+the+quest+for+neuroprotection+navigating+past+failure+to+future+success+A+review.">The science of cerebral ischemia and the quest for neuroprotection navigating past failure to future success A review.</a> Journal of Neurosurgery. 118, 1072-1085 (2013).</li><li>Vannucci, R. C., Perlman, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interventions+for+perinatal+hypoxic+ischemic+encephalopathy.">Interventions for perinatal hypoxic ischemic encephalopathy.</a> Pediatrics. 100, 1004-1014 (1997).</li><li>Chicha, L., 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=Stem+cells+for+brain+repair+in+neonatal+hypoxia&#8211;ischemia.">Stem cells for brain repair in neonatal hypoxia&#8211;ischemia.</a> Childs Nervous System. 30, 37-46 (2014).</li><li>Barks, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+controversies+in+hypothermic+neuroprotection.">Current controversies in hypothermic neuroprotection.</a> Seminars in Fetal and Neonatal. 13 (1), 30-34 (2008).</li><li>Jantzie, L. L., 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=Neonatal+ischemic+stroke+a+hypoxic+ischemic+injury+to+the+developing+brain.">Neonatal ischemic stroke a hypoxic ischemic injury to the developing brain.</a> Future Neurology. 3, 99-102 (2008).</li><li>James, A., Patel, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypoxic+ischaemic+encephalopathy.">Hypoxic ischaemic encephalopathy.</a> Paediatrics and Child Health. 24 (9), (2014).</li><li>Levine, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anoxic+ischemic+encephalopathy+in+rats.">Anoxic ischemic encephalopathy in rats.</a> The American Journal of Pathology. 36 (1), (1960).</li><li>Vannucci, S. 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=Experimental+stroke+in+the+female+diabetic+db+db+mouse.">Experimental stroke in the female diabetic db db mouse.</a> Journal of Cerebral Blood Flow &amp; Metabolism. 21, 52-60 (2001).</li><li>Sheldon, R., 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=Strain+related+brain+injury+in+neonatal+mice+subjected+to+hypoxia+ischemia.">Strain related brain injury in neonatal mice subjected to hypoxia ischemia.</a> Brain Research. 810, 114-122 (1998).</li><li>Adhami, F., 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=Cerebral+ischemia+hypoxia+induces+intravascular+coagulation+and+autophagy.">Cerebral ischemia hypoxia induces intravascular coagulation and autophagy.</a> American Journal of Pathology. 169 (2), 566-583 (2006).</li><li>Catana, C., 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=Simultaneous+in+vivo+positron+emission+tomography+and+magnetic+resonance+imaging.">Simultaneous in vivo positron emission tomography and magnetic resonance imaging.</a> Proceedings of the National Academy of Sciences. 105, 3705-3710 (2008).</li><li>Judenhofer, M. S., 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=Simultaneous+PET+MRI+a+new+approach+for+functional+and+morphological+imaging.">Simultaneous PET MRI a new approach for functional and morphological imaging.</a> Nature Medicine. 14, 459-465 (2008).</li><li>Wehrl, H. F., 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=Simultaneous+PET+MRI+reveals+brain+function+in+activated+and+resting+state+on+metabolic+hemodynamic+and+multiple+temporal+scales.">Simultaneous PET MRI reveals brain function in activated and resting state on metabolic hemodynamic and multiple temporal scales.</a> Nature Medicine. 19, 1184-1189 (2013).</li><li>Judenhofer, M. S., Cherry, S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Applications+for+preclinical+PET+MRI.">Applications for preclinical PET MRI.</a> Seminars in Nuclear Medicine. 43 (1), 19-29 (2013).</li><li>Wehrl, H. F., 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=Preclinical+and+Translational+PET/MR+Imaging.">Preclinical and Translational PET/MR Imaging.</a> Journal of Nuclear Medicine. 55, 11S-18S (2014).</li><li>Heiland, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diffusion+and+Perfusion+Weighted+MR+Imaging+in+Acute+Stroke+Principles+Methods+and+Applications.">Diffusion and Perfusion Weighted MR Imaging in Acute Stroke Principles Methods and Applications.</a> Imaging Decisions MRI. 7, 4-12 (2003).</li><li>Loubinoux, I., 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=Spreading+of+vasogenic+edema+and+cytotoxic+edema+assessed+by+quantitative+diffusion+and+T2+magnetic+resonance+imaging.">Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging.</a> Stroke. 28, 419-427 (1997).</li><li>Ouyang, Y., 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=Evaluation+of+2+[18F]fluoroacetate+kinetics+in+rodent+models+of+cerebral+hypoxia&#8211;ischemia.">Evaluation of 2 [18F]fluoroacetate kinetics in rodent models of cerebral hypoxia&#8211;ischemia.</a> Journal of Cerebral Blood Flow &amp; Metabolism. 34 (5), 836-844 (2014).</li><li>Kuhl, D. E., 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=Effects+of+stroke+on+local+cerebral+metabolism+and+perfusion+mapping+by+emission+computed+tomography+of+18FDG+and+13NH3.">Effects of stroke on local cerebral metabolism and perfusion mapping by emission computed tomography of 18FDG and 13NH3.</a> Annals of Neurology. 8, 47-60 (1980).</li><li>Planas, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+Brain+Imaging+in+Small+Animal+Stroke+Models+MRI+and+PET.">Noninvasive Brain Imaging in Small Animal Stroke Models MRI and PET.</a> Neuromethods. 47, 139-165 (2010).</li><li>Marik, 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=PET+of+glial+metabolism+using+2-18F-fluoroacetate.">PET of glial metabolism using 2-18F-fluoroacetate.</a> Journal of Nuclear Medicine. 50 (6), 982-990 (2009).</li><li>Mart&#237;n, 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=Depressed+glucose+consumption+at+reperfusion+following+brain+ischemia+does+not+correlate+with+mitochondrial+dysfunction+and+development+of+infarction:+an+in+vivo+positron+emission+tomography+study.">Depressed glucose consumption at reperfusion following brain ischemia does not correlate with mitochondrial dysfunction and development of infarction: an in vivo positron emission tomography study.</a> Current Neurovascular Research. 6, 82-88 (2009).</li><li>Carson, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET+physiological+measurements+using+constant+infusion.">PET physiological measurements using constant infusion.</a> Nuclear Medicine and Biology. 27, 657-660 (2000).</li><li>Greve, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+BOLD+effect.">The BOLD effect.</a> Methods in Molecular Biology. 771, 153-159 (2011).</li><li>Flores, J. E., 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+effects+of+anesthetic+agent+and+carrier+gas+on+blood+glucose+and+tissue+uptake+in+mice+undergoing+dynamic+FDG-PET+imaging+sevoflurane+and+isoflurane+compared+in+air+and+in+oxygen.">The effects of anesthetic agent and carrier gas on blood glucose and tissue uptake in mice undergoing dynamic FDG-PET imaging sevoflurane and isoflurane compared in air and in oxygen.</a> Molecular Imaging and Biology. 10, 192-200 (2008).</li><li>Delso, G., Ziegler, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET+MRI+system+design.">PET MRI system design.</a> European Journal of Nuclear Medicine and Molecular Imaging. 36, 86-92 (2009).</li></ol>

JM和SW是基因泰克的员工。

同时解剖MRI和动态DWI-MRI和[18 F] FDG PET数据成功地从实验动物中以下颈总动脉结扎缺氧挑战获得的。这代表了一个强有力的实验范例用于与在大脑局部缺血损伤相关联的快速变化的病理生理的多模成像和可以很容易地扩展到研究其它的PET放射性示踪剂（对于神经炎症的示例标记）和MRI序列，以及介入战略的影响期间或缺血性的挑战后不久。 期间在?...

在世界范围内，中风死亡的第二大原因和残疾1的一大原因。发生期间和之后急性中风事件生理生化事件的级联反应迅速，与组织的活力，最终的结果2含义发生。脑缺氧缺血（HI），这导致缺氧缺血性脑病（HIE），估计影响高达0.3％和足月和早产，分别3,4- 4％。死亡率在HIE患儿是约15％至20％。在HIE幸存者的25％，永久性并发症发生的伤害，包括智力低下，运动障碍，脑瘫和癫痫3,4的结果。以往的治疗干预还没有被证明值得采纳的护理标准，并达成共识尚未达成，最先进的方法，基于低温，有效降低发病率3,5。其他问题Ø˚F争夺包括低温和患者选择6给药方法。因此，对神经保护和神经复原的战略仍然是一个肥沃的地区研究7。 自1960年以来脑HI大鼠模型已经面世，并随后进行了调整，以小鼠8,9。由于模型和结扎的位置的性质，有对结果因在动物10之间侧支血流差异固有可变性。其结果是，这些车型往往比同类机型，如大脑中动脉闭塞（缺血），更变数。生理变化的实时测量已被证实与激光多普勒血流仪以及弥散加权成像11。脑血液流所观察到的帧内动物变性期间，并立即缺氧后，以及在急性成果，如梗死体积和神经赤字，建议同时采集多的数据和关联将是有益的。 在同时进行正电子发射断层扫描（PET）和磁共振成像（MRI）的最新进展已经允许在临床前成像12-14中的新的可能性。这些混合，结合系统临床前应用的潜在优势在文献15,16已经描述。例如，当事件如中风的每个实例本身表现独特，迅速变化的病理生理 - - 尽管许多临床前的问题可以通过成像个别动物顺序的或通过成像单独动物组，某些情况下加以处理，使其理想，甚至是必要使用同步测量。脑功能成像提供了这样一个例子，在这里同时2-脱氧-2-（18 F）氟ᴅ葡萄糖（[18 F-FDG）PET和布卢D-氧水平依赖（BOLD）MRI最近被证明在大鼠胡须刺激研究14。 在这里，我们展示了一个发生缺氧缺血性中风的大脑生理学是不是在稳定状态的过程中同时进行PET / MRI成像，但在缺氧的挑战，而不是迅速和不可逆的变化。变化水扩散，如通过MRI测定，通过从弥散加权成像（DWI）衍生的表观扩散系数（ADC）量化的，已被充分表征的冲程在临床和临床前数据17,18。在动物模型如MCAO，水在受影响的脑组织的扩散迅速下降是由于生物能量级联导致细胞毒性水肿18。在ADC这些急性变化也观察到脑缺氧缺血11,19的啮齿动物模型。 [18楼] FDG PET显像已应用于中风患者，以评估改变当地的冰川ucose代谢20，和一个小数目的体内动物研究还使用[18 F] FDG的21，包括在脑缺氧缺血模型22。总的来说，这些研究显示，缺血区减少葡萄糖的利用，尽管使用再灌注模型的一项研究发现，与后来的心肌梗塞发展23这些代谢的变化无关。这是相对于已与不可逆受损芯 21相关联的扩散变化。因此，为了能够获得笔划的进化过程中，来自于[18 F] FDG PET及DWI以同时的方式中的补充信息是很重要的，因为这是可能产生关于损伤的进展，产生的影响的有意义的信息治疗干预。我们在这里描述的方法很容易适合与各种PET示踪剂和MRI序列的使用。例如，[15 O] H 2 O宠物随着DWI和灌注加权图像（PWI）从MRI图像可以被用于进一步探索缺血半暗带的开发和验证行程摄像视野内的电流的技术。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Surgery</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Surgical scissors</td>
			<td>Roboz</td>
			<td>RS-5852</td>
			<td></td>
		</tr>
		<tr>
			<td>Forceps</td>
			<td>Roboz</td>
			<td>RS-5237</td>
			<td></td>
		</tr>
		<tr>
			<td>Hartman mosquito forceps</td>
			<td>Miltex</td>
			<td>7-26</td>
			<td></td>
		</tr>
		<tr>
			<td>2x McPherson suturing forceps, 8.5 cm</td>
			<td>Accurate Surgical &#38; Scientific Instruments</td>
			<td>4473</td>
			<td>It is useful to reduce the opening width with a band on the forceps used to hold the carotid artery</td>
		</tr>
		<tr>
			<td>6-0 silicone coated braided silk suture with 3/8 C-1 needle</td>
			<td>Covidien Sofsilk</td>
			<td>S-1172</td>
			<td></td>
		</tr>
		<tr>
			<td>Homeothermic blanket system</td>
			<td>Harvard Apparatus</td>
			<td>507220F</td>
			<td></td>
		</tr>
		<tr>
			<td>Super glue</td>
			<td>(Generic)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hypoxia</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Flowmeter for O2</td>
			<td>Alicat Scientific</td>
			<td>MC-500SCCM-D</td>
			<td></td>
		</tr>
		<tr>
			<td>Flometer for N2</td>
			<td>Alicat Scientific</td>
			<td>MC-5SLPM-D</td>
			<td></td>
		</tr>
		<tr>
			<td>O2 meter</td>
			<td>MSA</td>
			<td>Altair Pro</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Imaging</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>7.05 Tesla MRI System</td>
			<td>Bruker</td>
			<td>BioSpec</td>
			<td>20 cm inner bore diameter with gradient set. Paravision 5.1 software.</td>
		</tr>
		<tr>
			<td>Volume Tx/Rx 1H Coil, 35mm ID</td>
			<td>Bruker</td>
			<td>T8100</td>
			<td></td>
		</tr>
		<tr>
			<td>PET system</td>
			<td>(In-house)</td>
			<td></td>
			<td>4x24 LSO-PSAPD detectors, 
			10x10 LSO array per detector, 
			1.2mm crystal pitch and 14mm depth. 14 x 14 mm PSAPD. FOV: 60x35mm. 350-650 keV energy window. 16 ns timing window.</td>
		</tr>
		<tr>
			<td>Vessel cannulation Dumont forceps</td>
			<td>Roboz</td>
			<td>RS-4991</td>
			<td></td>
		</tr>
		<tr>
			<td>PE-10 polyethylene tubing</td>
			<td>BD Intramedic</td>
			<td>427401</td>
			<td></td>
		</tr>
		<tr>
			<td>Infusion pump</td>
			<td>Braintree Scientific</td>
			<td>BS-300</td>
			<td></td>
		</tr>
		<tr>
			<td>Animal monitoring &#38; gating equipment</td>
			<td>Small Animal Instruments Inc.</td>
			<td>Model 1025</td>
			<td>Only respiration monitoring used</td>
		</tr>
		<tr>
			<td>Animal bed with temperature regulation</td>
			<td>(In-house)</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

simultaneous pet/mri imaging during mouse cerebral hypoxia-ischemia

在缺氧脑缺氧缺血反映在受影响细胞生物能量扰动后组织水扩散和葡萄糖代谢的动态变化会发生。磁共振弥散加权成像（MRI）标识被损坏，造成无法恢复的区域，缺氧，缺血。在受影响的组织对葡萄糖的利用改变可以是可检测的正电子发射断层摄影术的2-脱氧-2-（18 F）的氟ᴅ葡萄糖（[18 F] FDG）摄取（PET）成像。由于损伤的动物模型的快速和可变性质，采集数据的两种模式的必须同时以有意义地关联的PET和MRI数据执行。此外，在缺氧缺血损伤由于血管差异的动物间变异性限制来分析多模态的数据和观察到的变化的一组，明智的做法，如果未在个体对象同时采集的数据的能力。该方法P反感这里允许一个之前在相同的动物获得两个扩散加权MRI和[18 F] FDG摄取数据，在此期间，为了询问即时的生理变化的缺氧攻击后。

图1显示了普通颈动脉的结扎正确之前，闭合伤口用6-0丝线缝合的结果。 在该方法中，从拍摄得到的数据是高度依赖于实验，这又决定，并且还决定由实验的限制包括图像捕获方案和设备设置的时间安排。这些及其他因素的进一步探讨在讨论部分。与本文描述的协议中，设备（图2A）的物理安装允许进行不间断的多模态图像采集之前，期?...

Watch this Scientific Journal Video about Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia at JoVE.com

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

这里介绍的方法使用同时正电子发射断层扫描和磁共振成像。在脑缺氧缺血模型，扩散和糖代谢的动态变化过程及伤后发生。在这个模型中不断变化和不可重复的损害就必须同时获得，如果有意义的多模态成像的数据是被收购。

同时PET / MRI成像在小鼠脑缺氧缺血

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

simultaneous-petmri-imaging-during-mouse-cerebral-hypoxia-ischemia

Research

JoVE Journal

Medicine

12.2K 次观看.  University of California, Davis. 这里介绍的方法使用同时正电子发射断层扫描和磁共振成像。在脑缺氧缺血模型，扩散和糖代谢的动态变化过程及伤后发生。在这个模型中不断变化和不可重复的损害就必须同时获得，如果有意义的多模态成像的数据是被收购。 

视频: Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Mouse Model of Middle Cerebral Artery Occlusion

Stroke is the most common fatal neurological disease in the United States 1. The majority of strokes (88%) result from blockage of blood vessels in the brain (ischemic stroke) 2. Since most ischemic strokes (~80%) occur in the territory of middle cerebral artery (MCA) 3, many animal stroke models that have been developed have focused on this artery. The intraluminal monofilament model of middle cerebral artery occlusion (MCAO) involves the insertion of a surgical filament into the external carotid artery and threading it forward into the internal carotid artery (ICA) until the tip occludes the origin of the MCA, resulting in a cessation of blood flow and subsequent brain infarction in the MCA territory 4. The technique can be used to model permanent or transient occlusion 5. If the suture is removed after a certain interval (30 min, 1 h, or 2 h), reperfusion is achieved (transient MCAO); if the filament is left in place (24 h) the procedure is suitable as a model of permanent MCAO. This technique does not require craniectomy, a neurosurgical procedure to remove a portion of skull, which may affect intracranial pressure and temperature 6. It has become the most frequently used method to mimic permanent and transient focal cerebral ischemia in rats and mice 7,8. To evaluate the extent of cerebral infarction, we stain brain slices with 2,3,5-triphenyltetrazolium chloride (TTC) to identify ischemic brain tissue 9. In this video, we demonstrate the MCAO method and the determination of infarct size by TTC staining.

We demonstrate in the video a method for producing a middle cerebral artery occlusion in adult mice using an intraluminal monofilament. We also show how to evaluate the extent of cerebral infarction by 2,3,5-triphenyltetrazolium chloride (TTC) staining.

大脑中动脉闭塞的小鼠模型

Stroke is the most common fatal neurological disease in the United States 1. The majority of strokes (88%) result from blockage of blood vessels in the ...

科研

医学

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to develop suitable animal models to study the events that unfold during ischemic insult. These techniques include transient or permanent, focal or global ischemia models using many different animal models, with the most common being rodents.
The permanent MCA ligation method which is also referred as pMCAo in the literature is used extensively as a focal ischemia model in rodents 1-6. This method was originally described for rats by Tamura et al. in 1981 7. In this protocol a craniotomy was used to access the MCA and the proximal regions were occluded by electrocoagulation. The infarcts involve mostly cortical and sometimes striatal regions depending on the location of the occlusion. This technique is now well established and used in many laboratories 8-13. Early use of this technique led to the definition and description of &#x201C;infarct core&#x201D; and &#x201C;penumbra&#x201D; 14-16, and it is often used to evaluate potential neuroprotective compounds 10, 12, 13, 17. Although the initial studies were performed in rats, permanent MCA ligation has been used successfully in mice with slight modifications 18-20 .
This model yields reproducible infarcts and increased post-survival rates. Approximately 80% of the ischemic strokes in humans happen in the MCA area 21 and thus this is a very relevant model for stroke studies. Currently, there is a paucity of effective treatments available to stroke patients, and thus there is a need for good models to test potential pharmacological compounds and evaluate physiological outcomes. This method can also be used for studying intracellular hypoxia response mechanisms in vivo. 
Here, we present the MCA ligation surgery in a C57/BL6 mouse. We describe the pre-surgical preparation, MCA ligation surgery and 2,3,5 Triphenyltetrazolium chloride (TTC) staining for quantification of infarct volumes.

Middle cerebral artery (MCA) ligation is a technique to study focal cerebral ischemia in animal models. In this method, the middle cerebral artery is exposed by craniotomy and ligated by cauterization. This method gives highly reproducible infarct volumes and increased post-operative survival rates compared to other methods available.

在小鼠永久性大脑中动脉结扎术中的应用

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to ...

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health.
Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.
Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult 1,2, because oxygen consumption and delivery reach equilibrium after acute transients 3. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) 4,5.
With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

We combined frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation with diffuse correlation spectroscopy measures of cerebral blood flow index to estimate an index of oxygen metabolism. We tested the utility of this measure as a bedside screening tool to evaluate the health and development of the newborn brain.

婴幼儿的脑代谢和血流动力学的非侵入式光学测量

Perinatal brain injury remains a significant cause of infant mortality  and morbidity, but there is not yet an effective bedside tool that can  accurately ...

Utilizing a Cranial Window to Visualize the Middle Cerebral Artery During Endothelin-1 Induced Middle Cerebral Artery Occlusion

Creation of a cranial window is a method that allows direct visualization of structures on the cortical surface of the brain1-3. This technique can be performed in many locations overlying the rat cerebrum, but is most easily carried out by creating a craniectomy over the readily accessible frontal or parietal bones. Most frequently, we have used this technique in combination with the endothelin-1 middle cerebral artery occlusion model of ischemic stroke to quantify the changes in middle cerebral artery vessel diameter that occur with injection of endothelin-1 into the brain parenchyma adjacent to the proximal MCA4, 5. In order to visualize the proximal portion of the MCA during endothelin -1 induced MCAO, we use a technique to create a cranial window through the temporal bone on the lateral aspect of the rat skull (Figure 1). Cerebral arteries can be visualized either with the dura intact or with the dura incised and retracted. Most commonly, we leave the dura intact during visualization since endothelin-1 induced MCAO involves delivery of the vasoconstricting peptide into the brain parenchyma. This bypasses the need to incise the dura directly over the visualized vessels for drug delivery. This protocol will describe how to create a cranial window to visualize cerebral arteries in a step-wise fashion, as well as how to avoid many of the potential pitfalls pertaining to this method.

This article describes a method for visualizing rat cerebral arteries through a cranial window using temporal craniectomy in order to view proximal portions of the middle cerebral artery (Figure 1). This versatile method can be combined with various techniques of drug delivery to measure cerebral artery reactivity in vivo.

利用颅窗口，在可视化的大脑中动脉内皮素-1诱导大脑中动脉闭塞

Creation of a cranial window is a method that allows direct visualization of structures on the cortical surface of the brain1-3. This technique can be ...

In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma

Microglia, which are CNS-resident neuroimmune cells, transform their morphology and size in response to CNS damage, switching to an activated state with distinct functions and gene expression profiles. The roles of microglial activation in health, injury and disease remain incompletely understood due to their dynamic and complex regulation in response to changes in their microenvironment. Thus, it is critical to non-invasively monitor and analyze changes in microglial activation over time in the intact organism. In vivo studies of microglial activation have been delayed by technical limitations to tracking microglial behavior without altering the CNS environment. This has been particularly challenging during chronic neurodegeneration, where long-term changes must be tracked. The retina, a CNS organ amenable to non-invasive live imaging, offers a powerful system to visualize and characterize the dynamics of microglia activation during chronic disorders.
This protocol outlines methods for long-term, in vivo imaging of retinal microglia, using confocal ophthalmoscopy (cSLO) and CX3CR1GFP/+ reporter mice, to visualize microglia with cellular resolution. Also, we describe methods to quantify monthly changes in cell activation and density in large cell subsets (200-300 cells per retina). We confirm the use of somal area as a useful metric for live tracking of microglial activation in the retina by applying automated threshold-based morphometric analysis of in vivo images. We use these live image acquisition and analyses strategies to monitor the dynamic changes in microglial activation and microgliosis during early stages of retinal neurodegeneration in a mouse model of chronic glaucoma. This approach should be useful to investigate the contributions of microglia to neuronal and axonal decline in chronic CNS disorders that affect the retina and optic nerve.

In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma

Microglia activation and microgliosis are key responses to chronic neurodegeneration. Here, we present methods for in vivo, long-term visualization of retinal CX3CR1-GFP+ microglial cells by confocal ophthalmoscopy, and for threshold and morphometric analyses to identify and quantify their activation. We monitor microglial changes during early stages of age-related glaucoma.

视网膜胶质细胞活化的体内动力学在神经退行性疾病：共聚焦成像眼底及细胞形态计量小鼠青光眼

Microglia, which are CNS-resident neuroimmune cells, transform their morphology and size in response to CNS damage, switching to an activated state with ...

A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia

Stroke research has endured many setbacks in translating neuroprotective therapies into clinical practice. In contrast, the real-world therapy (tPA thrombolysis) rarely produces benefits in mechanical occlusion-based experimental models, which dominate preclinical stroke research. This split between the bench and bedside suggests the need to employ tPA-responsive models in preclinical stroke research. To this end, a simple and tPA-reactive thrombotic stroke model is invented and described here. This model consists of transient occlusion of the unilateral common carotid artery and delivery of 7.5% oxygen through a face mask in adult mice for 30 min, while maintaining the animal rectal temperature at 37.5 &#177; 0.5 &#176;C. Although reversible ligation of the unilateral carotid artery or hypoxia each suppressed cerebral blood flow only transiently, the combination of both insults caused lasting reperfusion deficits, fibrin and platelet deposition, and large infarct in the middle cerebral artery-supplied territory. Importantly, tail-vein injection of recombinant tPA at 0.5, 1, or 4 hr post-tHI (10 mg/kg) provided time-dependent reduction of the mortality rate and infarct size. This new stroke model is simple and can be standardized across laboratories to compare experimental results. Further, it induces thrombosis without craniectomy or introducing pre-formed emboli. Given these unique merits, the tHI model is a useful addition to the repertoire of preclinical stroke research.

Thromboembolic stroke models are vital tools for optimizing the recanalization therapy. Here we report a murine thrombotic stroke model based on transient cerebral hypoxic-ischemic (tHI) insult, which triggers thrombosis and infarction, and responds favorably to tissue plasminogen activator (tPA)-mediated fibrinolysis in a therapeutic window similar to those in stroke patients.

基于短暂性脑缺氧缺血性血栓性中风模型

Stroke research has endured many setbacks in translating neuroprotective therapies into clinical practice. In contrast, the real-world therapy (tPA ...

Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats

Encephalopathy of prematurity (EoP) is a term that encompasses the central nervous system (CNS) abnormalities associated with preterm birth. To best advance translational objectives and uncover new therapeutic strategies for brain injury associated with preterm birth, preclinical models of EoP must include similar mechanisms of prenatal global injury observed in humans and involve multiple components of the maternal-placental-fetal system. Ideally, models should produce a similar spectrum of functional deficits in the mature animal and recapitulate multiple aspects of the pathophysiology. To mimic human systemic placental perfusion defects, placental underperfusion and/or chorioamnionitis associated with pathogen-induced inflammation in early preterm birth, we developed a model of prenatal transient systemic hypoxia-ischemia (TSHI) combined with intra-amniotic lipopolysaccharide (LPS). In pregnant Sprague Dawley rats, TSHI via uterine artery occlusion on embryonic day 18 (E18) induces a graded placental underperfusion defect associated with increasing CNS damage in the fetus. When combined with intra-amniotic LPS injections, placental inflammation is increased and CNS damage is compounded with associated white matter, gait and imaging abnormalities. Prenatal TSHI and TSHI+LPS prenatal insults meet several of the criteria of an EoP model including recapitulating the intrauterine insult, causing loss of neurons, oligodendrocytes and axons, loss of subplate, and functional deficits in adult animals that mimic those observed in children born extremely preterm. Moreover, this model allows for the dissection of inflammation induced by divergent injury types.

Encephalopathy of prematurity encompasses the central nervous system abnormalities associated with injury from preterm birth. This report describes a clinically relevant rat model of in utero transient systemic hypoxia-ischemia and intra-amniotic lipopolysaccharide administration (LPS) that mimics chorioamnionitis, and the related impact of infectious stimuli and placental underperfusion on CNS development.

早产儿脑病建模使用产前缺氧缺血大鼠羊膜腔内毒素

Encephalopathy of prematurity (EoP) is a term that encompasses the central nervous system (CNS) abnormalities associated with preterm birth. To best ...

Combined Near-infrared Fluorescent Imaging and Micro-computed Tomography for Directly Visualizing Cerebral Thromboemboli

Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of stroke than relying on indirect measurements, and will be a potent and robust vascular research tool. We use an optical imaging approach that labels thrombi with a molecular imaging thrombus marker&#160;&#8212; a Cy5.5 near-infrared fluorescent (NIRF) probe that is covalently linked to the fibrin strands of the thrombus by the fibrin-crosslinking enzymatic action of activated coagulation factor XIIIa during the process of clot maturation. A micro-computed tomography (microCT)-based approach uses thrombus-seeking gold nanoparticles (AuNPs) functionalized to target the major component of the clot: fibrin. This paper describes a detailed protocol for the combined in vivo microCT and ex vivo NIRF imaging of thromboemboli in a mouse model of embolic stroke. We show that in vivo microCT and fibrin-targeted glycol-chitosan AuNPs (fib-GC-AuNPs) can be used for visualizing both in situ thrombi and cerebral embolic thrombi. We also describe the use of in vivo microCT-based direct thrombus imaging to serially monitor the therapeutic effects of tissue plasminogen activator-mediated thrombolysis. After the last imaging session, we demonstrate by ex vivo NIRF imaging the extent and the distribution of residual thromboemboli in the brain. Finally, we describe quantitative image analyses of microCT and NIRF imaging data. The combined technique of direct thrombus imaging allows two independent methods of thrombus visualization to be compared: the area of thrombus-related fluorescent signal on ex vivo NIRF imaging vs. the volume of hyperdense microCT thrombi in vivo.

This protocol describes the application of combined near-infrared fluorescent (NIRF) imaging and micro-computed tomography (microCT) for visualizing cerebral thromboemboli. This technique allows the quantification of thrombus burden and evolution. The NIRF imaging technique visualizes fluorescently labeled thrombus in excised brain, while the microCT technique visualizes thrombus inside living animals using gold-nanoparticles.

结合近红外荧光成像和微计算机断层扫描直接可视化脑血栓

Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of ...

Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model

Mutations in the CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation (CCM) in humans. Mouse models of CCM disease have been established by tamoxifen induced deletion of Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. An accurate and quantitative method to assess lesion burden and progression is essential to harness the full value of these animal models. Here, we demonstrate the induction of CCM disease in a mouse model and the use of the contrast enhanced X-ray micro computed tomography (micro-CT) method to measure CCM lesion burden in mouse brains. At postnatal day 1 (P1), we used 4-hydroxytamoxifen (4HT) to activate Cre recombinase activity from the Cdh5-CreErt2 transgene to cleave the floxed allele of Ccm2. CCM lesions in mouse brains were analyzed at P8. For micro-CT, iodine based Lugol&#39;s solution was used to enhance contrast in brain tissue. We have optimized the scan parameters and utilized a voxel dimension of 9.5 &#181;m, which lead to a minimum feature size of approximately 25 &#181;m. This resolution is sufficient to measure CCM lesion volume and number globally and accurately, and provide high-quality 3-D mapping of CCM lesions in mouse brains. This method enhances the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases.

This protocol demonstrates the induction of cerebral cavernous malformation disease in a mouse model and uses contrast enhanced micro computed tomography to measure lesion burden. This method enhances the value of established mouse models to study the molecular basis and potential therapies for cerebral cavernous malformation and other cerebrovascular diseases.

小鼠脑海绵体畸形的诱导及显微 CT 成像

Mutations in the CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation (CCM) in humans. Mouse models of CCM disease have ...

Middle Cerebral Artery Occlusion Allowing Reperfusion via Common Carotid Artery Repair in Mice

The ischemic stroke is a major cause of adult long-term disability and death worldwide. The current treatments available are limited, with only tissue plasminogen activator (tPA) as an approved drug treatment to target ischemic strokes. Current research in the field of ischemic stroke focuses on better understanding the pathophysiology of stroke, to develop and investigate novel pharmaceutical targets. Reliable experimental stroke models are crucial for the progression of potential treatments. The middle cerebral artery occlusion (MCAO) model is clinically relevant and the most frequently used surgical model of ischemic stroke in rodents. However, the outcomes of this model, such as lesion volume, are associated with high levels of variability, particularly in mice. The alternative MCAO model described here allows the reperfusion of the common carotid artery (CCA) and the increased perfusion of the middle cerebral artery (MCA) territory, using a tissue pad with fibrinogen-based sealant to repair the vessel, and the improved welfare of the mice by avoiding external carotid artery (ECA) ligation. This reduces the reliance on the Circle of Willis, which is known to be highly anatomically variable in mice. Representative data show that using this alternative surgical approach decreases the variability in lesion volumes between the traditional MCAO approach and the alternative approach described here.

Intraluminal filament occlusion of the middle cerebral artery is the most frequently used in vivo model of experimental stroke in rodents. An alternative surgical approach to allow common carotid artery repair is performed here, which allows the reperfusion of the common carotid artery and a full reperfusion to the middle cerebral artery territory.

颅内动脉闭塞允许经普通颈动脉修复再灌注的研究

The ischemic stroke is a major cause of adult long-term disability and death worldwide. The current treatments available are limited, with only tissue ...