This work was made possible with funding from the Canadian Institutes of Health Research (CIHR) and the authors would like to thank CIHR for their funding support.

适当的制度动物伦理委员会应在开始试验之前批准所有的行为过程。这里描述的所有动物工作被批准由西方大学动物使用小组委员会和遵循加拿大议会关于动物保护的准则。这些动物实验在光照​​阶段进行。 1.气缸任务毛前肢运动评定<ol><li>设备安装<ol><li>获得一个有机玻璃圆筒的多孔盖，将容纳用于实验的大鼠的大小。圆筒的尺寸不应该允许大鼠来饲养时达到顶峰，它应该允许壁和大鼠的鼻子和老鼠的尾根部之间2厘米。圆柱体的标准尺寸为23厘米，直径40厘米的高度为6个月大的（400-600克）的大鼠。 </li><li>放置一个反射镜在与气缸坐在PLE缸设备低于45°角xiglas站立或支持上表中最高约为30厘米一些其他形式。 </li><li>设置在三脚架上的摄像机在适当的距离，以可视化的圆筒的整个直径在视频摄像机上的反射镜。 </li><li>打开照明调光器设置，并在房间内（ 即小批量，微妙的音乐）播放白噪声，减少突然大声喧哗的效果。这将有助于鼓励流动，防止结冰因大声喧哗。 </li></ol></li><li>实验步骤<ol><li>移动老鼠进实验房间30分钟前先试用开始以不变大鼠的房间音乐播放和调光照明。 </li><li>写在白色中小板相应的动物和审判信息（ 如动物的数量，每天的时间表和审判数）。把这个板的镜子前。 </li><li>摄像机与白板在镜子前的新闻记录，拿起基地附近Ò大鼠F中的尾部，放置老鼠在汽缸中并固定盖子。支座在气缸的一侧，以避免与录像干扰。 </li><li>从在镜子前除去白色板，并让摄像机记录在气缸5分钟在大鼠（使用一个定时器来从当白色板被移除记录5分钟）。这是一次试验。 </li><li>试用后，清洁用纸巾和水的缸。 </li><li>重复步骤1.2.2-1.2.5两次共实现三个试验。应该有20-30分钟审间的时间来习惯的几率降低到气缸。在这段时间中，运行对其它大鼠气缸试验。 </li></ol></li><li>视频分析<ol><li>导入摄像机文件到视频编辑软件（ 如 iMovie中） </li><li>编译成影片剪辑每次试验。视频静音的体积和降低视频的速度到原来的25％。 </li><li>算前肢联系人的数量与缸的左，右前肢的壁。对于同时左，右接触，算上这些前肢联系人为"既"。请记住，视频是通过反射镜，这似乎是在视频的左前肢对应于现实动物的右前肢记录。 </li><li>计算使用下列公式％的用户使用受影响的前肢（对侧中风）:[{（受影响触点+½双边接触）/总数联系人}×100]。野生型群体和无笔划的转基因组的表现被认为比较组，以评估疾病引起的问题的介绍。 </li></ol></li></ol> 2.梁行走任务粗大运动评估<ol><li>设备安装<ol><li>获得平滑的密封木梁即2厘米宽，大约120厘米长（一200-600摹老鼠最​​佳宽度）。 </li><li>将两个表或搁置取消其100厘米分开。每个单元的表面应当高出地面约40厘米</li><li>固定梁的两端表或使用磁带搁架表面。约1m不支持梁长的，现在应该升高40厘米高出地面。 </li><li>设置一个视频摄像机放在底座上，捕捉光束的整个长度。为了增强图像对比度，可以考虑使用大白鼠时引入黑色背景梁后面。 </li></ol></li><li>实验步骤<ol><li>移动老鼠进实验房间30分钟前先试用开始以不变大鼠的房间音乐播放和调光照明。 </li><li>放置老鼠的家笼或环境富集管在梁的一端与放置老鼠在梁的另一端。 </li><li>进行几个非记录奔跑之前实验性试验两天。让大鼠探索区域和通过保持大鼠的基部引导朝向光束大鼠的尾巴。 </li><li>一旦大鼠已越过横梁，移动笼或管到梁和重复的另一端。当大鼠在任一方向自由地穿过光束，训练会话结束。保持训练次数运行所有动物中是一致的。 </li><li>写在白色中小板相应的动物和审判信息（ 如动物的数量，每天的时间表和审判数）。录像带，这白板梁后面的墙壁。 </li><li>放置老鼠的家笼或环境富集油管在梁的一端。 </li><li>按视频摄像机上的记录和由尾和地点在光束相对的家笼或管道的端部的基部挑大鼠起来。 </li><li>记录试验中，当老鼠已成功完成遍历高架梁的全长从而结束的全部。如果老鼠中途暂停跨梁，轻轻浮渣老鼠尾巴的基部或轻轻触碰老鼠的尾巴以促进整个束运动。不要推进大鼠以任何方式。 </li><li>重新做临床试验，其中老鼠变成横盘，而在横梁上，多次停止行走或不一致散步。如果一只老鼠下降，并继续挂在横梁，轻轻舀起了老鼠，并把它放回束在秋季的位置，并继续进行审判。 </li><li>移动笼或管梁的另一端，改变审判＃在白板上，记录了随后的审判。 </li><li>重复此过程，直到总共6个试验已经完成，以被记录为每个方向3的试验。所有6个试验的老鼠可以在开始试验下一个老鼠之前被记录。 </li></ol></li><li>视频分析<ol><li>导入摄像机文件到视频编辑软件（ 如 iMovie中）。 </li><li>编译成影片剪辑每次试验和静音视频的音量。通过分析每一帧视频剪辑帧。 </li><li>数数总的步骤的大鼠花费行走梁的全长和左，右后肢和前肢滑倒的总数的总数量。野生型组的效果和无笔划的转基因组相比于共同病态组被认为是评估特有的共同病态条件赤字出现。 </li></ol></li></ol>莫里斯水迷宫海马依赖的空间学习和记忆参考<ol><li>设备安装<ol><li>固定上方的圆形池（149厘米直径的58厘米深）的中心的摄像机。与跟踪软件程序的池的轮廓正确对齐四个指定象限。 </li><li>装满水约36厘米深的圆形水池。水应该通过之前开始实验方案在几天填充池升温至室温。 </li><li>添加黑无毒丙烯酸涂料未直到水使用大白鼠时是不透明的。使用浅色，如白色，对于较深色的老鼠。 </li><li>环绕空白墙面，包括如果需要，房间隔断池。当在游泳池，大鼠不应该能够看到实验者。 </li><li>从不同颜色的海报板的切4大不同形状的空间感和每个指定的北，东，东南和西南地区池墙连接一个形状。这些线索应比池的边缘略高。 </li><li>打开收音机在低音量在西北象限，防止鼠从测试过程中意外大声喧哗而分心。 </li><li>将在目标象限中央的圆形平台（11.5厘米直径，表面2-3厘米水位以下）。 </li><li>关掉主房间的灯和对房间分隔的相反侧开启一个落地灯到池中照亮的区域。 </li></ol></li><li>计算机配置<ol&gt; <li>使用一种专为Morris水迷宫行为的任务，并成立协议实验开始前的跟踪程序。一个可能的方案的一个例子在图4中提供。 </li><li>设置连续4天用4试验各90秒的空间学习实验。 </li><li>设置每个30秒的2个独立的探测实验的第一个探测实验后的最后空间学习试用后24小时，1周。 </li><li>定在每天4个试验为连续2天线索学习试验启动第二探针实验后24小时。每次试验应在60秒的总。 </li><li>每个阶段中，设置检测顺序，使得有各试验对于任何给定的动物之间的20分钟试验间隔。其他动物可以在这个审间的间隔期间，只要每隔动物保持20分钟审间的间隔运行。 </li><li>确保平台位置是由实验者进行定义，而且所有其它区域被去由指定的平台位置处以罚款。 </li><li>设置程序来手动启动和结束每一次试验。 </li></ol></li><li>空间学习实验<ol><li>将在西南象限的圆形平台。它应与圆形指定"平台"上的计算机程序的象限区域对齐。 </li><li>泳池周围起始位置应该是随机的每只大鼠。代表每个治疗组中的所有开始位置。不从老鼠在任何模式空间学习试验提出允许探针测试过程中一个新的开始位置的东北位置开始。 </li><li>按住老鼠在它的尾巴基地，轻轻将其放置在水沿水池壁在指定的起始位置，迅速走出老鼠的视线。 </li><li>具有其它实验者只要老鼠是在水中开始跟踪软件。计时器应该从0开始的跟踪程序计数。 </l我&gt; <li>如果老鼠所处的平台，有其他实验者在计算机上停止审判和检索之前离开老鼠的平台上至少30秒。如果试验被停止在计算机上之前，老鼠跳下平台，庭审仍在继续。 </li><li>如果老鼠没有找到在规定的试用时间的平台，用你的手（或者使得老鼠跟着你的手或尾巴的基地指导鼠）引导老鼠平台。保持在平台上的大鼠30秒。 </li><li>它的尾巴的基地到实验者的手臂被覆盖着毛巾或让老鼠爬上一个便携式表面取下池的老鼠。 </li><li>重复步骤3.3.3-3.3.7总共每只大鼠4试验。应20分钟对各大鼠的试验间隔。 </li><li>返回老鼠他们家笼热灯下至少10分钟后的大鼠的最后空间学习的审判。 </li><li>继续EXA通过空间学习的第4天CT相同的空间学习方案2的一天。 </li><li>在2-4天，就不再持有该平台上的老鼠。允许老鼠坐在平台上无需援助30秒，实验者的视线。这期间有时一天后试验来完成。 </li></ol></li><li>探针实验<ol><li>从池中取出的平台。确保以前的平台位置保持计算机（圆圈在西南象限）上定义。 </li><li>在广场沿水池壁水鼠在东北位置，并迅速走出老鼠的视线。小说采用东北起始位置保证了老鼠召回独立于以前训练的起始位置平台位置。 </li><li>具有其它实验者只要老鼠是在水中开始跟踪软件。计时器应该从0开始对跟踪软件计数。 </li><li>检索来自大鼠它的尾巴根部池西南象限并按住毛巾覆盖手臂或让老鼠爬上一个便携式表面。 </li><li>返回老鼠他们家笼热灯下至少10分钟以下各组大鼠的探测试验。 </li><li> 1周后重复这个实验（步骤3.4.1-3.4.5）。 </li></ol></li><li>线索学习实验<ol><li>用胶带固定在支架上是高大的平台在8.5厘米，直径4厘米的白色球状线索（线索的总高度为12.5厘米）。球形线索的顶部将至少为8.5厘米以上水位。 </li><li>周围池壁删除空间线索。 </li><li>随机化平台位置，并开始位置对每个组中的每个老鼠。所有平台和开始位置应表示为每个处理组。 </li><li>放置平台在指定平台区和在跟踪软件定义。 </li><li>放置老鼠的水一起在t池的壁他指定的开始位置，并迅速走出老鼠的视线。 </li><li>具有其它实验者只要老鼠是在水中开始跟踪软件。计时器应该从0开始对跟踪软件计数。 </li><li>一旦老鼠到达平台，拥有其他实验者停止电脑上试用。如果老鼠跳下平台，庭审仍在继续。检索鼠之前，允许大鼠坐平台上15秒。 </li><li>它的尾巴的基地检索从池中的老鼠并按住毛巾覆盖手臂或让老鼠爬上一个便携式表面。 </li><li>检查下一大鼠平台位置和平台移动到在跟踪软件限定的相应区域。 </li><li>重复步骤3.5.4-3.5.9以下3项试验。应该有15分钟的试验间隔。 </li><li>返回老鼠他们家笼热灯下至少10分钟以下各组大鼠的国际泳联升线索学习的审判。 </li><li>继续为线索学习第2天相同的协议。 </li></ol></li><li>数据分析 注意:在区域中花费时间，距离在区域中，平均车速，经常使用的条目入区和时间来首次进入区段数游历。 <ol><li>分析的时间和距离，到达平台区和每空间天的平均速度和线索分别学习。对于探测实验，分析潜伏期首次进入目标区域作为原始时间或探头1％的变化来探测2。 </li></ol></li></ol>

<ol>
	<li>Auld, D., Kornecook, T., Bastianetto, S., Quirion, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alzheimer's+disease+and+the+basal+forebrain+cholinergic+system:+relations+to+&#946;-amyloid+peptides,+cognition,+and+treatment+strategies.">Alzheimer's disease and the basal forebrain cholinergic system: relations to &#946;-amyloid peptides, cognition, and treatment strategies.</a> Prog Neurobiol. 68 (3), 209245 (2002).</li><li>Huang, Y., Mucke, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alzheimer+Mechanisms+and+Therapeutic+Strategies.">Alzheimer Mechanisms and Therapeutic Strategies.</a> Cell. 148 (6), (2012).</li><li>Querfurth, H., LaFerla, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alzheimer's+disease.">Alzheimer's disease.</a> New Engl J Med. 362 (4), 329-344 (2010).</li><li>Karran, E., Mercken, M., Strooper, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+amyloid+cascade+hypothesis+for+Alzheimer's+disease:+an+appraisal+for+the+development+of+therapeutics.">The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics.</a> Nat Rev Drug Discov. 10 (9), 698-712 (2011).</li><li>Akiyama, H., 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=Inflammation+and+Alzheimer's+disease.">Inflammation and Alzheimer's disease.</a> Neurobiol Aging. 21 (3), (2000).</li><li>Butterfield, D., Drake, J., Pocernich, C., Castegna, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+of+oxidative+damage+in+Alzheimer's+disease+brain:+central+role+for+amyloid+&#946;-peptide.">Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid &#946;-peptide.</a> Trends Mol Med. 7 (12), 548554 (2001).</li><li>Kalaria, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+cerebral+ischemia+in+Alzheimer's+disease.">The role of cerebral ischemia in Alzheimer's disease.</a> Neurobiol Aging. 21 (2), 321-330 (2000).</li><li>Selkoe, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alzheimer's+disease:+genes,+proteins,+and+therapy.">Alzheimer's disease: genes, proteins, and therapy.</a> Physiol Rev. 81 (2), 741-766 (2001).</li><li>Snowdon, D. 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=Brain+infarction+and+the+clinical+expression+of+alzheimer+disease:+The+nun+study.">Brain infarction and the clinical expression of alzheimer disease: The nun study.</a> JAMA. 277 (10), 813 (1997).</li><li>Clarke, 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=Overexpression+of+APP+provides+neuroprotection+in+the+absence+of+functional+benefit+following+middle+cerebral+artery+occlusion+in+rats.">Overexpression of APP provides neuroprotection in the absence of functional benefit following middle cerebral artery occlusion in rats.</a> Eur J Neurosci. 26 (7), 1845-1852 (2007).</li><li>Whitehead, S., Hachinski, V., Cechetto, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interaction+Between+a+Rat+Model+of+Cerebral+Ischemia+and+&#946;-Amyloid+Toxicity+Inflammatory+Responses.">Interaction Between a Rat Model of Cerebral Ischemia and &#946;-Amyloid Toxicity Inflammatory Responses.</a> Stroke. 36 (1), 107-112 (2005).</li><li>Agca, 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=Development+of+transgenic+rats+producing+human+&#946;-amyloid+precursor+protein+as+a+model+for+Alzheimer's+disease:+Transgene+and+endogenous+APP+genes+are+regulated+tissue-specifically.">Development of transgenic rats producing human &#946;-amyloid precursor protein as a model for Alzheimer's disease: Transgene and endogenous APP genes are regulated tissue-specifically.</a> BMC Neuroscience. 9 (1), 28 (2008).</li><li>Bayona, N. A., Gelb, A. W., Jiang, Z., Wilson, J. X., Urquhart, B. L., Cechetto, D. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Propofol+neuroprotection+in+cerebral+ischemia+and+its+effects+on+low-molecular-weight+antioxidants+and+skilled+motor+tasks.">Propofol neuroprotection in cerebral ischemia and its effects on low-molecular-weight antioxidants and skilled motor tasks.</a> Anesthesiology. 100 (5), 1151-1159 (2004).</li><li>Langdon, K., Clarke, J., Corbett, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+exposure+to+high+fat+diet+is+bad+for+your+brain:+exacerbation+of+focal+ischemic+brain+injury.">Long-term exposure to high fat diet is bad for your brain: exacerbation of focal ischemic brain injury.</a> Neuroscience. 182, 82-87 (2011).</li><li>Brownlow, M., 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=Partial+rescue+of+memory+deficits+induced+by+calorie+restriction+in+a+mouse+model+of+tau+deposition.">Partial rescue of memory deficits induced by calorie restriction in a mouse model of tau deposition.</a> Behav Brain Res. 271, 7988 (2014).</li><li>Halagappa, V., 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=Intermittent+fasting+and+caloric+restriction+ameliorate+age-related+behavioral+deficits+in+the+triple-transgenic+mouse+model+of+Alzheimer's+disease.">Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease.</a> Neurobiol Dis. 26 (1), (2007).</li><li>Maalouf, M., Rho, J., Mattson, 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+neuroprotective+properties+of+calorie+restriction,+the+ketogenic+diet,+and+ketone+bodies.">The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies.</a> Behav Brain Res. 59 (2), (2008).</li><li>Tillerson, J. 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=Forced+limb-use+effects+on+the+behavioral+and+neurochemical+effects+of+6-hydroxydopamine.">Forced limb-use effects on the behavioral and neurochemical effects of 6-hydroxydopamine.</a> Neuroscience. 21 (12), 4427-4435 (2001).</li><li>Sierksma, 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=Improvement+of+spatial+memory+function+in+APPswe/PS1dE9+mice+after+chronic+inhibition+of+phosphodiesterase+type+4D.">Improvement of spatial memory function in APPswe/PS1dE9 mice after chronic inhibition of phosphodiesterase type 4D.</a> Neuropharmacology. 77, (2013).</li><li>D'Hooge, R., De Deyn, P. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Applications+of+the+Morris+water+maze+in+the+study+of+learning+and+memory.">Applications of the Morris water maze in the study of learning and memory.</a> Behav Brain Res. 36 (1), 60-90 (2001).</li><li>Vorhees, C., Williams, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Morris+water+maze:+procedures+for+assessing+spatial+and+related+forms+of+learning+and+memory.">Morris water maze: procedures for assessing spatial and related forms of learning and memory.</a> Nat Protoc. 1 (2), 848-858 (2006).</li></ol>

作者宣称，他们没有竞争的经济利益。

中风和阿尔茨海默氏病的结果中很明显的行为的病症可影响这两个马达和根据各状况的严重程度的认知功能的组合。因此，有必要利用各种行为任务，以确定这些条件的个别贡献，以及提供一些洞察在共病态状况合并的和潜在的互动效果。呈现的数据证明三个成本效率，时间效率的和敏感的行为任务，以评估在一个新颖共同病态APP21转基因大鼠中风模型运动功能和海马依赖性空间学习和参考记忆?...

阿尔茨海默氏病（AD）是老年人人口痴呆和衰弱的神经变性疾病的最普遍的形式。组织病理学上，AD呈现为淀粉样蛋白斑，神经原纤维缠结和神经元的损失。淀粉样蛋白斑由已经通过由β分泌酶和γ分泌酶1,2,3淀粉样前体蛋白（APP）的改变的蛋白水解切割产生的β-淀粉样肽（Aβ）的主要。裂解产物，Aβ，在大脑中沉积产生病理淀粉样蛋白斑和对脑，可导致特性学习障碍和记忆丧失毒性作用。所有的这些步骤一起被称为"淀粉样蛋白级联假说"3,4。当调查广告时这个假设是很重要的，已被发现的其他细胞变化先于从原来的淀粉样蛋白级联途径偏离这些斑块地层。这些其他细胞变化被认为有助于早期记忆丧失，学习障碍和之前斑块形成3,5,6参与AD其它认知功能障碍。 随着AD越来越普遍，为开发AD的危险因素正成为研究的一个非常重要的焦点。虽然年龄是AD的散发性形式的主要危险因素，其他危险因素已被识别，包括中风7,8。中风不仅是一个危险因素，但它也可以加剧已经存在痴呆。例如，临床上，AD的进展已被证明是谁曾经历中风9例差。此外，增加的APP表达和Aβ积聚已Aβ毒性与诱发中风10,11结合的实验动物模型中找到。由于存在中风和AD之间的这种重要的相互作用，这是至关重要的，这两种病症进一步研究在共同病态模式，可以更好地了解病理生理学和行为在这两个条件牵连。 调查共同病态条件下，一个合适的模型，必须开发，其中中风可以与Aβ相互作用以产生AD样病理。对于第一次，使用具有并入其DNA中的突变的人APP基因的APP21转基因大鼠实现AD一种合适的型号。突变是瑞典双错义和印第安纳单错义突变，这都被在公元4,8,12家族形式牵连。在没有额外的侮辱，而不发展特色Aβ斑块或神经原纤维这种大鼠模型的年龄缠结12。因此，在努力以诱导AD样行为病理学，小冲程被引入右纹状体模仿小皮层下笔划常常存在于痴呆病人9。在APP21转基因RA的行程吨体现了共同病态条件，并允许不同类型的两种疾病状况牵连行为变化的研究。特别地，该感应AD样病理和认知缺陷的成年大鼠允许我们调查前述AD的最早的分子和认知改变。 由于该目标是确定的行为的变化的第一个迹象，并且自两冲程和AD具有非常明显的行为病状，研究共同病态模型时，行为任务需要评估各种行为表型。有很多，可以做分析运动和认知行为在涉及各种范例和设备的啮齿动物模型相对敏感测试电池。要具体分析前肢及后肢运动功能，气缸任务和梁步行任务已落实来检测运动障碍，并在这个模型监测运动。专门设计用来评估细FO等敏感任务relimb运动技能（ 即楼梯任务和单颗粒到达任务）要求食物匮乏11,13,14。为了避免任何对疾病的病理15,16,17食物匮乏的已知作用，这些测试已被视为不适合这项研究。气缸任务评估了一个新的环境中饲养过程中自发利用老鼠的前肢，可检测大鼠前肢之间的不对称性单侧中风10,18。这个任务的一个主要的好处是，该装置可用于其他行为任务，如Porsolt强迫游泳任务19。相反在气缸任务，光束步行任务还可以后肢和前肢电机控制的分析，除了locmotion 10,14。平衡木行走包括运动部件，组件平衡和熟练的脚的位置。这两个测试都是成本效益，简单，时间效率和阐明中风和AD对D的影响<html> ifferences肢体功能。 除了运动功能的改变，AD涉及记忆障碍，可以出现在疾病进展的早期阶段。当在啮齿动物模型寻址AD样病理，至关重要的是，海马依赖性学习和记忆的评估，因为海马是一个重要的脑结构很大程度上影响在公元2。海马是空间学习和记忆，其功能的重要脑区能够在啮齿动物使用各种迷宫范式进行测试。其中，针对不同疾病的啮齿动物模型中使用最广泛的迷宫任务是Morris水迷宫20。 Morris水迷宫利用空间线索协助大鼠在定位的静止隐藏平台和当平台被移除测试空间参考存储器。水迷宫设置的一个有价值的好处是，它是高度适应取决于提出研究问题20。 帐篷"&gt;这是第一次，所描述的技术已经被用于评估运动和认知功能的中风和AD的新的共病的大鼠模型。在一个APP21转基因大鼠模型，涉及小笔。共同发病率是通过诱导来实现血管中的纹状体的血管收缩以产生APP21转基因大鼠的小行程，该行程模型已经很好地建立在公元11的可替换的大鼠模型中的共同病态状态。进展到这种新颖的APP21转基因大鼠模型意产生更平移有价值的模型。虽然行为任务使用一个共同病态冲程和AD大鼠模型描述，这些任务可进一步应用于中风的其它模型或其他神经系统疾病的模型（ 即帕金森病）。一般描述的方法将广泛适用于这些其他疾病状态，但行为时间表和范式可能基础上，提出资源需要改动问题操作搜索和型号。除了是适应性强，所描述的任务是有效地展现次要缺陷的同时，还具有成本和时间效率。

<table border="0" cellpadding="0" cellspacing="0" width="817">
	<tbody>
		<tr height="125">
			<td height="125" style="height:125px;width:216px;">Cylinder</td>
			<td style="width:115px;">Western University</td>
			<td style="width:167px;">Plexiglas Cylinder 
			Cylinder Diameter: 23 cm 
			Cylinder Height: 40 cm 
			Platform Height: 30 cm 
			Mirror Length: 35 cm 
			Mirror Width: 26.5 cm</td>
			<td style="width:320px;">This was made specifically by Western University Machine Services for our lab. Please contact your own chosen manufacturer to design this product.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Handheld Video Camera</td>
			<td style="width:115px;">JVC</td>
			<td style="width:167px;">GZ-E200</td>
			<td style="width:320px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Video Camera Tripod</td>
			<td style="width:115px;">Slik</td>
			<td style="width:167px;">F163</td>
			<td style="width:320px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">AM/FM Clock Radio</td>
			<td style="width:115px;">Sylvania</td>
			<td style="width:167px;">SCR1388</td>
			<td style="width:320px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">White Board</td>
			<td style="width:115px;">Walmart</td>
			<td style="width:167px;">Width: 71.12 cm 
			Height: 55.88 cm</td>
			<td style="width:320px;">These can be purchased at any store (i.e. Walmart, University bookstores)</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Dry-erase Marker</td>
			<td style="width:115px;">Expo</td>
			<td style="width:167px;">Expo Dry-erase Original Marker</td>
			<td style="width:320px;">These can be purchased at any store (i.e. Walmart, University bookstores)</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Wooden Beam</td>
			<td style="width:115px;">Rona</td>
			<td style="width:167px;">Plywood 
			Width: 2 cm 
			Length: 100cm</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">VWR General Purpose Laboratory Tape</td>
			<td style="width:115px;">VWR Intl.</td>
			<td style="width:167px;">89097-920</td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">iMovie &#39;11</td>
			<td style="width:115px;">Apple Inc.</td>
			<td style="width:167px;">Version 9.0.9 (1795)</td>
			<td style="width:320px;">This is the version used in this manuscript, but any other iMovie version or video editing software could be used.</td>
		</tr>
		<tr height="44">
			<td height="44" style="height:44px;width:216px;">Morris Water Maze Pool with Platform</td>
			<td style="width:115px;">Stoelting Co.</td>
			<td style="width:167px;">60136/60035</td>
			<td style="width:320px;">These are not the exact products used in the video, but these are essentially identical.</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Platform Cue</td>
			<td style="width:115px;">-</td>
			<td style="width:167px;">-</td>
			<td style="width:320px;">The platform cue used was created using a small metal stand and white spherical foam ball. These can likely be purchased at any store with home improvement materials (i.e. Walmart, Rona etc.)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Mainstays 71&#34; Floor Lamp</td>
			<td style="width:115px;">Walmart</td>
			<td>HW-F0377SLV</td>
			<td style="width:320px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">ANY-Maze Behavioural Tracking Software</td>
			<td style="width:115px;">Stoelting Co.</td>
			<td style="width:167px;">60000</td>
			<td style="width:320px;">There are ANY-maze&#174; bundles that include the camera with or without a computer and accessories.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Compact Video Camera</td>
			<td style="width:115px;">Logitech</td>
			<td style="width:167px;">V-U0023</td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Laptop</td>
			<td style="width:115px;">Hewlett-Packard</td>
			<td style="width:167px;">HP&#174; Pavilion dv6 Notebook PC</td>
			<td style="width:320px;">Laptop Specifics: AMD A6-3420M APU with Radeon&#8482; HD Graphics 1.50 GHz, 6.00 GB RAM, 64-bit operating system.</td>
		</tr>
		<tr height="62">
			<td height="62" style="height:63px;width:216px;">Americana Non-toxic Acrylic Paint</td>
			<td style="width:115px;">DecoArt</td>
			<td>DAO67-9</td>
			<td style="width:320px;">This can be ordered on the DecoArt site or purchased in store at DecoArt&#174; retailers.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Poster Board</td>
			<td style="width:115px;">Walmart</td>
			<td>PA-1961</td>
			<td style="width:320px;"></td>
		</tr>
	</tbody>
</table>

motor and hippocampal dependent spatial learning and reference memory assessment in a transgenic rat model of alzheimer's disease with stroke

阿尔茨海默氏病（AD）是一种使人衰弱的神经变性疾病，其导致神经变性和记忆丧失。而年龄是AD的主要危险因素，中风也被牵连作为危险因素和一种加剧因素。在恶化卒中相关的电动机控制和AD相关的认知缺陷中风和AD结果的共病时相比单独各条件。为了模拟中风和AD，AD的新的转基因大鼠模型中，与淀粉样蛋白前体蛋白结合到它的DNA（涉及AD的发展的关键蛋白质）的突变形式的组合条件下，被赋予一个小单方面纹状体中风。 对于笔触和AD的组合模式，即评估中风有关的电机控制，运动和AD相关的认知功能行为测试必须执行。气缸任务涉及到评估自发前肢电机使用具有成本效益，多功能设备。在此任务，将大鼠放置在圆筒形装置，其中所述鼠将自发后部和联系其前肢汽缸的壁。这些接触被认为是前肢电机使用，在测试过程中经过视频分析量化。实施另一项经济高效的电机任务是梁行走任务，评估前肢控制，后肢控制和运动。此任务涉及跨木梁允许肢体运动控制的评估，通过前肢单，后肢滑倒分析大鼠行走。学习和记忆的评估完成后用Morris水迷宫这一行为模式。该协议始于空间学习，从而使老鼠找到一个固定的平台隐藏。空间学习后，该平台被去除，短期和长期的空间参考存储器进行评估。所有这三个任务是行为上的差异敏感，在28天内对这一模式完成，使这对digm时间效率和成本效益。

所描述的行为任务被用来表明笔划的阿尔茨海默氏病的APP21转基因大鼠模型中的作用。行程和APP21转基因的组合，预计将导致患肢更大的运动障碍，以及增加记忆障碍。 气缸任务评估毛前肢运动功能和被表示为使用受影响的前肢的。此外，光束的步行任务用于特异性评估后肢运动功能和运动。由于行程是在右纹状体诱导，左前?...

Watch this Scientific Journal Video about Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke at JoVE.com

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

调查在一个新颖模型共同病态阿尔茨海默氏病（AD）和中风的条件，都描述了三种行为任务评估两个电动机控制和认知行为。这些任务包括梁行走任务，气缸任务和Morris水迷宫。

汽车和海马依赖空间学习和记忆参考评估与中风阿尔茨海默氏病的转基因大鼠模型

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk ...

motor-hippocampal-dependent-spatial-learning-reference-memory

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Medicine

10.1K 次观看.  Western University. 调查在一个新颖模型共同病态阿尔茨海默氏病（AD）和中风的条件，都描述了三种行为任务评估两个电动机控制和认知行为。这些任务包括梁行走任务，气缸任务和Morris水迷宫。 

视频: Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

Examining the Characteristics of Episodic Memory using Event-related Potentials in Patients with Alzheimer's Disease

Our laboratory uses event-related EEG potentials (ERPs) to understand and support behavioral investigations of episodic memory in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Whereas behavioral data inform us about the patients' performance, ERPs allow us to record discrete changes in brain activity. Further, ERPs can give us insight into the onset, duration, and interaction of independent cognitive processes associated with memory retrieval. In patient populations, these types of studies are used to examine which aspects of memory are impaired and which remain relatively intact compared to a control population. The methodology for collecting ERP data from a vulnerable patient population while these participants perform a recognition memory task is reviewed. This protocol includes participant preparation, quality assurance, data acquisition, and data analysis. In addition to basic setup and acquisition, we will also demonstrate localization techniques to obtain greater spatial resolution and source localization using high-density (128 channel) electrode arrays.

The methodology for collecting high-density event-related potential data while patients with Alzheimer's disease perform a recognition memory task is reviewed. This protocol will include subject preparation, quality assurance, data acquisition, and data analysis.

情节记忆的特点，采用事件相关电位研究在阿尔茨海默氏症患者

Our laboratory uses event-related EEG potentials (ERPs) to understand and support behavioral investigations of episodic memory in patients with amnestic ...

科研

医学

Endothelin-1 Induced Middle Cerebral Artery Occlusion Model for Ischemic Stroke with Laser Doppler Flowmetry Guidance in Rat

Stroke is the number one cause of disability and third leading cause of death in the world, costing an estimated $70 billion in the United States in 20091, 2. Several models of cerebral ischemia have been developed to mimic the human condition of stroke. It has been suggested that up to 80% of all strokes result from ischemic damage in the middle cerebral artery (MCA) area3. In the early 1990s, endothelin-1 (ET-1) 4 was used to induce ischemia by applying it directly adjacent to the surface of the MCA after craniotomy. Later, this model was modified 5 by using a stereotaxic injection of ET-1 adjacent to the MCA to produce focal cerebral ischemia. The main advantages of this model include the ability to perform the procedure quickly, the ability to control artery constriction by altering the dose of ET-1 delivered, no need to manipulate the extracranial vessels supplying blood to the brain as well as gradual reperfusion rates that more closely mimics the reperfusion in humans5-7. On the other hand, the ET-1 model has disadvantages that include the need for a craniotomy, as well as higher variability in stroke volume8. This variability can be reduced with the use of laser Doppler flowmetry (LDF) to verify cerebral ischemia during ET-1 infusion. Factors that affect stroke variability include precision of infusion and the batch of the ET-1 used6. Another important consideration is that although reperfusion is a common occurrence in human stroke, the duration of occlusion for ET-1 induced MCAO may not closely mimic that of human stroke where many patients have partial reperfusion over a period of hours to days following occlusion9, 10. This protocol will describe in detail the ET-1 induced MCAO model for ischemic stroke in rats. It will also draw attention to special considerations and potential drawbacks throughout the procedure.

Several animal models of cerebral ischemia have been developed to simulate the human condition of stroke. This protocol describes the endothelin-1 (ET-1) induced middle cerebral artery occlusion (MCAO) model for ischemic stroke in rats. In addition, important considerations, advantages, and shortcomings of this model are discussed.

内皮素-1诱导大脑中动脉闭塞模型缺血性中风激光多普勒血流仪在大鼠指导

Stroke is the number one cause of disability and third leading cause of death in the world, costing an estimated $70 billion in the United States in ...

A Zebrafish Model of Diabetes Mellitus and Metabolic Memory

Diabetes mellitus currently affects 346 million individuals and this is projected to increase to 400 million by 2030. Evidence from both the laboratory and large scale clinical trials has revealed that diabetic complications progress unimpeded via the phenomenon of metabolic memory even when glycemic control is pharmaceutically achieved. Gene expression can be stably altered through epigenetic changes which not only allow cells and organisms to quickly respond to changing environmental stimuli but also confer the ability of the cell to "memorize" these encounters once the stimulus is removed. As such, the roles that these mechanisms play in the metabolic memory phenomenon are currently being examined.
We have recently reported the development of a zebrafish model of type I diabetes mellitus and characterized this model to show that diabetic zebrafish not only display the known secondary complications including the changes associated with diabetic retinopathy, diabetic nephropathy and impaired wound healing but also exhibit impaired caudal fin regeneration. This model is unique in that the zebrafish is capable to regenerate its damaged pancreas and restore a euglycemic state similar to what would be expected in post-transplant human patients. Moreover, multiple rounds of caudal fin amputation allow for the separation and study of pure epigenetic effects in an in vivo system without potential complicating factors from the previous diabetic state. Although euglycemia is achieved following pancreatic regeneration, the diabetic secondary complication of fin regeneration and skin wound healing persists indefinitely. In the case of impaired fin regeneration, this pathology is retained even after multiple rounds of fin regeneration in the daughter fin tissues. These observations point to an underlying epigenetic process existing in the metabolic memory state. Here we present the methods needed to successfully generate the diabetic and metabolic memory groups of fish and discuss the advantages of this model.

Metabolic memory is the phenomenon by which diabetic complications persist and progress unimpeded even after euglycemia is achieved pharmaceutically. Here we describe a diabetes mellitus zebrafish model which is unique in that it allows for the examination of the mitotically transmissible epigenetic components of metabolic memory in vivo.

斑马鱼模型的糖尿病和代谢记忆

Diabetes mellitus currently affects 346 million individuals and this is projected to increase to 400 million by 2030. Evidence from both the laboratory ...

Permanent Cerebral Vessel Occlusion via Double Ligature and Transection

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow (ischemia) 1. Middle cerebral artery (MCA) delivers a great majority of blood to the lateral surface of the cortex 2, is the most common site of human stroke 3, and ischemia within its territory can result in extensive dysfunction or death 1,4,5. Survivors of ischemic stroke often suffer loss or disruption of motor capabilities, sensory deficits, and infarct. In an effort to capture these key characteristics of stroke, and thereby develop effective treatment, a great deal of emphasis is placed upon animal models of ischemia in MCA.
Here we present a method of permanently occluding a cortical surface blood vessel. We will present this method using an example of a relevant vessel occlusion that models the most common type, location, and outcome of human stroke, permanent middle cerebral artery occlusion (pMCAO). In this model, we surgically expose MCA in the adult rat and subsequently occlude via double ligature and transection of the vessel. This pMCAO blocks the proximal cortical branch of MCA, causing ischemia in all of MCA cortical territory, a large portion of the cortex. This method of occlusion can also be used to occlude more distal portions of cortical vessels in order to achieve more focal ischemia targeting a smaller region of cortex. The primary disadvantages of pMCAO are that the surgical procedure is somewhat invasive as a small craniotomy is required to access MCA, though this results in minimal tissue damage. The primary advantages of this model, however, are: the site of occlusion is well defined, the degree of blood flow reduction is consistent, functional and neurological impairment occurs rapidly, infarct size is consistent, and the high rate of survival allows for long-term chronic assessment.

Permanent Cerebral Vessel Occlusion via Double Ligature and Transection

We describe a highly reproducible method for the permanent occlusion of a rodent major cerebral blood vessel. This technique can be accomplished with very little peripheral damage, minimal blood loss, a high rate of long-term survival, and consistent infarct volume commensurate with the human clinical population.

永久性脑血管闭塞<em&gt;通过</em&gt;双人结扎横断

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow ...

A Murine Model of Subarachnoid Hemorrhage

In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice.

A standardized mouse model of subarachnoid hemorrhage by intraluminal Circle of Willis perforation is described. Vessel perforation and subarachnoid bleeding are monitored by intracranial pressure monitoring. In addition various vital parameters are recorded and controlled to maintain physiologic conditions.

蛛网膜下腔出血的小鼠模型

In this video publication a standardized mouse model of subarachnoid  hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of  Willis ...

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are exacerbated when significant brain atrophy and age-related white matter changes (e.g. Leukoaraiosis) are present. Lesion Explorer (LE) is an accurate and reliable neuroimaging pipeline specifically developed to address such issues commonly observed on MRI of Alzheimer's disease and normal elderly. The pipeline is a complex set of semi-automatic procedures which has been previously validated in a series of internal and external reliability tests1,2. However, LE's accuracy and reliability is highly dependent on properly trained manual operators to execute commands, identify distinct anatomical landmarks, and manually edit/verify various computer-generated segmentation outputs.
LE can be divided into 3 main components, each requiring a set of commands and manual operations: 1) Brain-Sizer, 2) SABRE, and 3) Lesion-Seg. Brain-Sizer's manual operations involve editing of the automatic skull-stripped total intracranial vault (TIV) extraction mask, designation of ventricular cerebrospinal fluid (vCSF), and removal of subtentorial structures. The SABRE component requires checking of image alignment along the anterior and posterior commissure (ACPC) plane, and identification of several anatomical landmarks required for regional parcellation. Finally, the Lesion-Seg component involves manual checking of the automatic lesion segmentation of subcortical hyperintensities (SH) for false positive errors.
While on-site training of the LE pipeline is preferable, readily available visual teaching tools with interactive training images are a viable alternative. Developed to ensure a high degree of accuracy and reliability, the following is a step-by-step, video-guided, standardized protocol for LE's manual procedures.

Lesion Explorer (LE) is a semi-automatic, image-processing pipeline developed to obtain regional brain tissue and subcortical hyperintensity lesion volumetrics from structural MRI of Alzheimer's disease and normal elderly. To ensure a high level of accuracy and reliability, the following is a video-guided, standardized protocol for LE's manual procedures.

病变资源管理器:一个视频引导，标准化为老年痴呆症准确，可靠的MRI衍生Volumetrics和正常老年人协议

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are ...

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or &#39;neuronal-like&#39; cell culture systems are commonly utilized. While&#160;these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

We have developed a brain slice model which can be used to examine molecular mechanisms involved in excitotoxicity-mediated brain injury.&#160;This technique generates viable mature brain tissue and reduces animal numbers required for experimentation, whilst keeping the neuronal circuitry, cellular interactions, and postsynaptic compartments partly intact.

脑Microslices的兴奋性刺激作为<em&gt;在体外</em&gt;中风模型

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson&#39;s disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.
Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson&#39;s Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

Adaptive deep brain stimulation (aDBS) is effective for Parkinson&#8217;s disease, improving symptoms and reducing power consumption compared to conventional deep brain stimulation (cDBS). In aDBS we track a local field potential biomarker (beta oscillatory amplitude) in real time and use this to control the timing of stimulation.

控制帕金森氏症与自适应深部脑刺激

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time ...

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this is only partially explained by traditional CVD risk factors. Vascular dysfunction is an important non-traditional risk factor, characterized by vascular endothelial dysfunction (most commonly assessed as impaired endothelium-dependent dilation [EDD]) and stiffening of the large elastic arteries. While various techniques exist to assess EDD and large elastic artery stiffness, the most commonly used are brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV), respectively. Both of these noninvasive measures of vascular dysfunction are independent predictors of future cardiovascular events in patients with and without kidney disease. Patients with CKD demonstrate both impaired FMDBA, and increased aPWV. While the exact mechanisms by which vascular dysfunction develops in CKD are incompletely understood, increased oxidative stress and a subsequent reduction in nitric oxide (NO) bioavailability are important contributors. Cellular changes in oxidative stress can be assessed by collecting vascular endothelial cells from the antecubital vein and measuring protein expression of markers of oxidative stress using immunofluorescence. We provide here a discussion of these methods to measure FMDBA, aPWV, and vascular endothelial cell protein expression.

The degree of vascular dysfunction and contributing physiological mechanisms can be assessed in patients with chronic kidney disease by measuring brachial artery flow-mediated dilation, aortic pulse-wave velocity, and vascular endothelial cell protein expression.

血管功能在慢性肾脏疾病的评估

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this ...

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

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing and treating this complication using experimental models of spinal cord ischemia. The model described here demonstrates varying degrees of paraplegia that relate to the length of occlusion following thoracic aortic occlusion in a rat spinal cord ischemia model.
A 2-Fr. balloon-tipped catheter was advanced through the femoral artery into the descending thoracic aorta until the catheter tip was placed at the left subclavian artery in anesthetized male Sprague-Dawley rats. Spinal cord ischemia was induced by inflating the catheter balloon. After a set period of occlusion (9, 10, or 11 min), the balloon was deflated. Neurologic assessment was performed using the motor deficit index at 24 h after surgery, and the spinal cord was harvested for histopathological examination.
Rats that underwent 9 min of aortic occlusion showed mild and reversible motor impairment in the hind limb. Rats subjected to 10 min of aortic occlusion presented with moderate but reversible motor impairment. Rats subjected to 11 min of aortic occlusion displayed complete and persistent paralysis. The motor neurons in the spinal cord sections were more preserved in rats subjected to shorter duration of aortic occlusion.
Researchers can achieve a reproducible hind limb motor deficit following thoracic aortic occlusion using this spinal cord ischemia model.

This study demonstrates the technique to make a minimally invasive and easily reproducible model of spinal cord ischemia in rats. Various degrees of hind limb motor deficit can be produced by controlling the aortic occlusion time.

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 ...