这项研究得到了日本医学研究与开发机构 （AMED） 在疾病研究综合神经技术脑图 （Brain/MINDS） 项目（资助号 JP23dm0207001）下的部分支持。

本研究经 RIKEN（日本埼玉县）动物实验委员会批准 （W2023-2-041） 进行，并根据动物实验机构指南进行。在本研究中，使用了 6 只雌性狨猴 （2-6 岁）。
1. 开始治疗的标准
<ol><li>当符合以下任何一项标准时开始治疗: i） 体重< 300 克或每月体重减少 >20 克;ii） 低白蛋白血症（血清白蛋白 < 3.8 g/dL）;iii） 贫血（血细胞比容< 35%）;iv） 无 艰难梭菌、肠致病性 大肠杆菌或肠道原生动物的慢性腹泻;v） 肌肉质量明显减少。 注意:由于脱水和随后的血液浓缩伴随着 WMS，受影响动物的血清白蛋白和血细胞比容值可能会人为升高。</li>
</ol>2. 口服
<ol><li>将 0.1 mL 铁制剂（参见 材料表）与一块海绵蛋糕混合。</li>
	<li>将土豆泥喂给处理过的狨猴。 注意: 确保处理过的狨猴已完全吞下醪糟。</li>
</ol>3. 皮下给药
<ol><li>轻轻握住尾巴，将受 WMS 影响的狨猴捕捉到家笼中。</li>
	<li>用另一只手从后面握住动物的上半身。</li>
	<li>将动物带到治疗室。</li>
	<li>让动物紧贴助手的胸部或手臂。</li>
	<li>用酒精棉签清洁动物的背部区域。</li>
	<li>使用 0.1 G 针头将 26 mL 氨甲环酸（5% 溶液，参见 材料表）皮下注射到背部，每周 5 次。</li>
	<li>使用 5.0 G 针头皮下注射 0.1 mL 乳酸林格氏液（见 材料表）和 26 mL 维生素制剂（见 材料表），每周 3 次。 注意:每次注射应在 1 分钟内在每个不同的位置进行。</li>
</ol>4. 氨基酸制剂的静脉给药
<ol><li>轻轻握住尾巴，将受 WMS 影响的狨猴捕捉到家笼中。</li>
	<li>用另一只手从后面握住动物的上半身。</li>
	<li>将动物带到治疗室。</li>
	<li>让助手握住双臂的根部来约束动物的上半身，用另一只手握住双腿的根部来约束下半身。让助手将束缚动物下半身的拇指放在动物膝盖的前侧，以防止其弯曲。</li>
	<li>用酒精棉签清洁动物的小腿。</li>
	<li>使用 2.0 G 蝶形针每周 3 次，通过大隐静脉静脉注射 27 mL 氨基酸制剂（参见 材料表）。 注意:注射必须尽可能缓慢地进行，最长可达 2 分钟。</li>
	<li>注射后，让助手用脱脂棉按压该区域，直到出血停止。</li>
</ol>5. 体重测量
<ol><li>治疗后（静脉内和/或皮下注射），每周用手提箱称量动物体重以监测体重。 注意:大约在同一时间称量狨猴的体重，因为体重会受到食物存在的影响。</li>
</ol>6. 全血细胞计数 （CBC） 分析和血清化学测试
<ol><li>轻轻握住尾巴，将受 WMS 影响的狨猴捕捉到家笼中。</li>
	<li>用另一只手从后面握住动物的上半身。</li>
	<li>将动物带到治疗室。</li>
	<li>让助手握住双臂的根部来约束动物的上半身，用另一只手握住任一条腿的根部来约束下半身。</li>
	<li>请医生握住没有束缚的动物腿。</li>
	<li>用酒精棉签清洁动物的腹股沟区域。</li>
	<li>每月使用 0.4 G 针头从股静脉收集 26 mL 血液。</li>
	<li>使用 0.05 mL 血样进行 CBC 分析，包括血细胞比容。</li>
	<li>让其余的血样在室温下静置 1 小时，并以 1,800 × g 离心 20 分钟。</li>
	<li>使用血清进行化学测试，包括白蛋白。 注:通过尽量减少血清化学测试的参数数量，可以减少血样的体积。根据个体狨猴的情况调整血样的体积。</li>
</ol>

一种治疗消瘦性狨猴综合征的有效改良方法

<ol><li>Baxter, V. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Serum+albumin+and+body+weight+as+biomarkers+for+the+antemortem+identification+of+bone+and+gastrointestinal+disease+in+the+common+marmoset%5BTitle%5D)+AND+%22PLoS+ONE%22%5BJournal%5D)">Serum albumin and body weight as biomarkers for the antemortem identification of bone and gastrointestinal disease in the common marmoset.</a> PLoS ONE. 8 (12), e82747(2013).</li>
<li>Brack, M., Rothe, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Chronic+tubulointerstitial+nephritis+and+wasting+disease+in+marmosets+%28Callithrix+jacchus%29%5BTitle%5D)+AND+%22Vet+Pathol%22%5BJournal%5D)">Chronic tubulointerstitial nephritis and wasting disease in marmosets (Callithrix jacchus).</a> Vet Pathol. 18, Suppl 6 45-54 (1981).</li>
<li>Chalifoux, L. V., Bronson, R. T., Escajadillo, A., McKenna, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((An+analysis+of+the+association+of+gastroenteric+lesions+with+chronic+wasting+syndrome+of+marmosets%5BTitle%5D)+AND+%22Vet+Pathol+Suppl%22%5BJournal%5D)">An analysis of the association of gastroenteric lesions with chronic wasting syndrome of marmosets.</a> Vet Pathol Suppl. 7, 141-162 (1982).</li>
<li>Logan, A. C., Khan, K. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Clinical+pathologic+changes+in+two+marmosets+with+wasting+syndrome%5BTitle%5D)+AND+%22Toxicol+Pathol%22%5BJournal%5D)">Clinical pathologic changes in two marmosets with wasting syndrome.</a> Toxicol Pathol. 24 (6), 707-709 (1996).</li>
<li>Ludlage, E., Mansfield, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Clinical+care+and+diseases+of+the+common+marmoset+%28Callithrix+jacchus%29%5BTitle%5D)+AND+%22Comp+Med%22%5BJournal%5D)">Clinical care and diseases of the common marmoset (Callithrix jacchus).</a> Comp Med. 53 (4), 369-382 (2003).</li>
<li>Ross, C. N., Davis, K., Dobek, G., Tardif, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Aging+phenotypes+of+common+marmosets+%28Callithrix+jacchus%29%5BTitle%5D)+AND+%22J+Aging+Res%22%5BJournal%5D)">Aging phenotypes of common marmosets (Callithrix jacchus).</a> J Aging Res. 2012, 567143(2012).</li>
<li>Yoshimoto, T., Niimi, K., Takahashi, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Curative+effects+of+tranexamic+acid+with+supportive+measures+on+wasting+marmoset+syndrome%5BTitle%5D)+AND+%22Comp+Med%22%5BJournal%5D)">Curative effects of tranexamic acid with supportive measures on wasting marmoset syndrome.</a> Comp Med. 66 (6), 1-6 (2016).</li>
<li>Niimi, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Measurement+of+the+%CE%B11-proteinase+inhibitor+%28%CE%B11-antitrypsin%29+of+common+marmoset+and+intestinal+protein+loss+in+wasting+syndrome%5BTitle%5D)+AND+%22Biosci+Rep%22%5BJournal%5D)">Measurement of the α1-proteinase inhibitor (α1-antitrypsin) of common marmoset and intestinal protein loss in wasting syndrome.</a> Biosci Rep. 39 (7), 20190562(2019).</li>
<li>Otovic, P., Smith, S., Hutchinson, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+use+of+glucocorticoids+in+marmoset+wasting+syndrome%5BTitle%5D)+AND+%22J+Med+Primatol%22%5BJournal%5D)">The use of glucocorticoids in marmoset wasting syndrome.</a> J Med Primatol. 44 (2), 53-59 (2015).</li>
<li>Turner, P. V., Brabb, T., Pekow, C., Vasbinder, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Administration+of+substances+to+laboratory+animals%3A+routes+of+administration+and+factors+to+consider%5BTitle%5D)+AND+%22J+Am+Assoc+Lab+Anim+Sci%22%5BJournal%5D)">Administration of substances to laboratory animals: routes of administration and factors to consider.</a> J Am Assoc Lab Anim Sci. 50 (5), 600-613 (2011).</li>
<li>Lewis, S. M., Hotchkiss, C. E., Ullrey, D. E. Chapter 13. Nutrition and nutritional diseases. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aLewis%2C+SM+%22The+Laboratory+Primates%22">The Laboratory Primates</a>. Wolfe-Coote, S. , 181-208 (2005).</li>
</ol>

作者没有需要披露的利益冲突。

2016 年，我们报道了氨甲环酸联合支持措施是 WMS 的有效治疗方法，这是第一篇证明 WMS 治疗不使用糖皮质激素的报告。在人类中，糖皮质激素被认为是治疗 IBD 最有效的药物。然而，普莱多唑酮是最常用的糖皮质激素之一，由于其不良反应，不适合 WMS 治疗。尽管据报道，布地奈德是一种糖皮质激素，用于治疗 WMS9，但该疗法对急性 WMS 的动物相对无效。氨甲环酸是一种具有抗炎作用的纤溶酶抑制剂，在我们原来的方法中没有发现明显的副作用。然而，尽管最初的治疗方案肯定有效，但它给动物和护理人员带来了沉重的负担。
在本研究中，进行了改良的 WMS 治疗方法，以减少动物的生理负荷和照顾者的工作量。在改良的方法中，氨甲环酸的给药途径发生了变化 （从腹膜内到皮下），这有助于降低腹部器官损伤的风险。在本实验步骤中未稀释氨甲环酸溶液，以降低污染风险和制备时间。在原始方法中，静脉注射 3.0 mL 氨基酸制剂。然而，体积有点大，因为建议以 5.0 mL/kg 作为10 次推注给药。因此，在修改后的方法中体积减小。 
该方案中使用的维生素制剂含有维生素 B 和 C。在原始方法中，0.5 mL 的维生素制剂含有 2.5 mg 盐酸硫胺素，是实验室饲养的断奶后非人灵长类动物所需量的 2.5 倍11。在本方法中，施用 0.1 mL 维生素制剂，其中含有 1.0 mg 盐酸硫胺素。在改良的方法中，铁制剂和氨甲环酸溶液的给药频率降低，这有助于减轻动物和护理人员的负担。 
如代表性结果部分所述，修改后的方法具有显著的处理效果。平均治疗期限为 37.8 ± 25.34 d，短于原始方法 （56 d）。由于狨猴对精神压力敏感，因此长期治疗对动物产生相反的效果，例如食欲下降。因此，我们建议护理人员不仅应根据每个参数的值，还应根据动物的行为来全面决定治疗终止的时间。

消耗性狨猴综合征 （WMS） 是一种严重的疾病，是圈养普通狨猴群落所特有的。主要症状是体重减轻、肌肉量减少、贫血、低白蛋白血症和慢性肠炎 1,2,3,4。一些研究报告说，60.5% 的安乐死圈养狨猴有慢性肠炎的证据 5,31-44% 的死亡与这种疾病有关6。这种疾病的高患病率需要其有效治疗。
2016 年，我们报道了氨甲环酸联合支持措施是 WMS7 的有效治疗方法。此外，这种处理显着减轻了受 WMS 影响的狨猴的肠道蛋白丢失8。虽然最初的治疗方案肯定有效，但它包括一些高容量的静脉注射、高剂量的维生素制剂和日常约束。由于狨猴容易受到手捕捉和束缚，因此这些动作必须不那么频繁。因此，我们的目标是通过一些修改来减轻动物的负担。
在本文中，我们将提供修改后的方法:每周 5 次皮下注射未稀释的氨甲环酸（代替腹膜内注射 5 倍稀释的氨甲环酸溶液，每周 7 次），静脉注射 2.0 mL 氨基酸制剂（代替 3.0 mL），皮下注射维生素 0.1 mL（代替 0.5 mL）， 和每周 5 次口服铁制剂（而不是每周 7 次）。

<table><tbody><tr><td>1.0 mL Syringe</td><td>Terumo Corporation, Tokyo, Japan</td><td>SS-01T</td><td>For subcutaneously injection of Tranexamic acid</td></tr><tr><td>10 mL Syringe</td><td>Terumo Corporation, Tokyo, Japan</td><td>SS-10SZ</td><td>For Intravenous Administration of Amino acid formulation</td></tr><tr><td>26 G Needle</td><td>Terumo Corporation, Tokyo, Japan</td><td>NN-2613S</td><td>For subcutaneously injection</td></tr><tr><td>27 G Butterfly Needle Type D</td><td>Terumo Corporation, Tokyo, Japan</td><td>SV-27DL</td><td>For Intravenous Administration of Amino acid formulation</td></tr><tr><td>5 mL Syringe</td><td>Terumo Corporation, Tokyo, Japan</td><td>SS-05SZ</td><td>For subcutaneously injection of Ringer&#039;s lactate and Vitamin formulation</td></tr><tr><td>Aminoleban Injection</td><td>Otsuka Pharma Factory Inc., Tokyo, Japan</td><td>1942</td><td>For subcutaneously injection of Ringer&#039;s lactate and Vitamin formulation</td></tr><tr><td>C-PARA</td><td>Takata Pharma Co., Ltd., Saitama, Japan</td><td>120-31960-0</td><td>Vitamin formulation</td></tr><tr><td>FCV Liquid</td><td>Minerva Corporation, Saitama, Japan</td><td></td><td>Iron formulation</td></tr><tr><td>Lactec Injection</td><td>Otsuka Pharma Factory Inc., Tokyo, Japan</td><td>0714</td><td>Ringer&amp;rsquo;s lactate&amp;nbsp;</td></tr><tr><td>Vasolamin Injection</td><td>Meiji Seika Pharma Co., Ltd., Tokyo, Japan</td><td>DBASOS</td><td>Tranexamic acid</td></tr></tbody></table>

modification of the treatment methods for wasting marmoset syndrome with tranexamic acid and supportive measures

消耗性狨猴综合征 （WMS） 是圈养普通狨猴 （Callithrix jacchus） 群体的一种严重疾病，与高死亡率相关。WMS 的具体原因尚不清楚，有效的治疗方法很少。之前，我们报道了一种氨甲环酸疗法联合支持措施是 WMS 的有效治疗方法。在本研究中，我们描述了修改后的方法:每周 5 次皮下注射 0.1 mL 5% 氨甲环酸，每周 3 次静脉注射 2.0 mL 氨基酸制剂，每周 3 次，5.0 mL 乳酸林格氏液与 0.1 mL 维生素制剂，每周 3 次皮下注射，以及每周 5 次口服 0.1 mL 铁制剂。我们还描述了如何通过大隐静脉静脉内施用溶液，并带有束缚动物的尖端，以及口服和皮下给药的详细方法。修改后的方法具有与原始 WMS 处理方法相当的效率。

修改后的治疗方法导致受 WMS 影响的狨猴的血细胞比容（图 1A）、血清白蛋白（图 1B）和体重（图 1C）增加。血细胞比容 （P < 0.05，Wilcoxon 匹配对符号秩检验）、血清白蛋白 （P < 0.05，Wilcoxon 匹配对符号秩检验）和体重 （P < 0.05，Wilcoxon 匹配对符号秩检验）在治疗前后观察到显著差异。
还观察到对外观的治疗效果。 图 2 显示了受 WMS 影响的狨猴的外观。治疗前观察到袢蛤、弓背、粗糙的皮毛（图 2A）和脱发（图 2B），而治疗后未见异常外观（图 2C、D）。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66768/66768fig01.jpg"> 图 1:接受改良治疗的狨猴的血细胞比容、血清白蛋白和体重的变化（治疗前与治疗后）。 （A） 血细胞比容值，（B） 血清白蛋白值，以及 （C） 体重。虚线表示条件值。缩写: Htc = 血细胞比容;Alb = 血清白蛋白;BW = 体重。 <a href="https://www.jove.com/files/ftp_upload/66768/66768fig01large.jpg" target="_blank">请单击此处查看此图的较大版本。</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66768/66768fig02.jpg"> 图 2:受 WMS 影响的狨猴的代表性外观。 （A） 预处理动物的外观:观察到指臼状、弓形背部和粗糙的皮毛。（B） 预处理动物的尾巴:观察到脱发。（C） 治疗后动物的外观。（D） 治疗后动物的尾巴。缩写:WMS = 消耗性狨猴综合症。 <a href="https://www.jove.com/files/ftp_upload/66768/66768fig02large.jpg" target="_blank">请单击此处查看此图的较大版本。</a>

作者聚焦:为消耗性狨猴综合征 （WMS） 开发更安全、更有效的治疗方案

在这里，我们描述了氨甲环酸治疗消耗性狨猴综合征 （WMS，也称为炎症性肠病 （IBD） 样疾病）的改良治疗方法。我们还介绍了如何口服、皮下和静脉注射治疗药物。

氨甲环酸治疗消耗性狨猴综合征的改良及支持措施

Wasting marmoset syndrome (WMS), a serious disease in captive common marmoset (Callithrix jacchus) colonies, is associated with a high mortality rate. The ...

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JoVE Journal

Medicine

Modification of the Treatment Methods for Wasting Marmoset Syndrome with Tranexamic Acid and Supportive Measures

991 次观看.  RIKEN Center for Brain Science. 我们最初的消瘦狨猴综合症治疗方案绝对有效，但它给狨猴及其护理人员带来了沉重的负担。在这项研究中，我们修改了方案以减少动物的生理负荷和护理人员的工作量。我们使用氨甲环酸的方案有几个优点。与类固醇疗法相比，它不会引起明显的副作用或导致耐受性。此外，皮下给药比腹膜内注射更安全，因为没有损伤腹部器官的风险。我们...

视频: 作者聚焦:为消耗性狨猴综合征 （WMS） 开发更安全、更有效的治疗方案

Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique

Mouse models are of special interest in research since a wide variety of monoclonal antibodies and commercially defined inbred and knockout strains are available to perform mechanistic in vivo studies. While heart transplantation models using a suture technique were first successfully developed in rats, the translation into an equally widespread used murine equivalent was never achieved due the technical complexity of the microsurgical procedure. In contrast, non-suture cuff techniques, also developed initially in rats, were successfully adapted for use in mice1-3. This technique for revascularization involves two major steps I) everting the recipient vessel over a polyethylene cuff; II) pulling the donor vessel over the formerly everted recipient vessel and holding it in place with a circumferential tie. This ensures a continuity of the endothelial layer, short operating time and very high patency rates4.
Using this technique for vascular anastomosis we performed more than 1,000 cervical heart transplants with an overall success rate of 95%. For arterial inflow the common carotid artery and the proximal aortic arch were anastomosed resulting in a retrograde perfusion of the transplanted heart. For venous drainage the pulmonary artery of the graft was anastomosed with the external jugular vein of the recipient5.
Herein, we provide additional details of this technique to supplement the video.

The murine cervical heart transplantation model is well suited for immunological as well as ischemia reperfusion injury studies. We modified the procedure using a non-suture cuff technique and performed more than 1,000 successful transplants with this approach.
Herein, we provide additional details of this technique to supplement the video.

用改进的袖套法小鼠颈部心脏移植模型

Mouse models are of special interest in research since a wide variety of monoclonal antibodies and commercially defined inbred and knockout strains are ...

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医学

A Common Marmoset Model of Mother-Infant Intervention for Breastfeeding Disorders in the Presence of Paternal Inhibition and Maternal Neglect

Parents&#39; psychological stress during the perinatal and neonatal periods continues to increase in an environment of declining birthrates, aging populations, and shrinking family sizes. The increase in child abuse and neglect cases, most likely by inexperienced and insufficiently knowledgeable parents, necessitates education on childcare and intervention techniques in nursing and midwifery training. In particular, attachment formation early in life between mother and infant is crucial. To accurately teach sensitive and comprehensive information on intervention techniques for mother-child attachment formation, realistic videos, and educational materials are necessary. Although pseudoeducational materials are available, they might be limited in explaining complex realism, particularly to support breastfeeding that involves both parents and child and that encourages interaction between the two.
In a previous study in a common marmoset (Callithrix jacchus) model, we experimentally controlled infant feeding and nurturing through 24 h of constant sensing and collected 1 month of quantitative data on psychological indices that possibly translated to psychological development. Age-dependent dynamic visualization of these data by multivariate analyses inferred causal relationships between early parental feeding and psychobiological rhythm formation. In the same primate model, we identified a spontaneous case of breastfeeding failure in which the father inhibited his neonatal infant&#39;s feeding and the mother appeared to abandon nurturing, leading to clinically significant weight loss in the infant.
Thus, we explored intervention techniques to promote mother-infant interaction. The mother was trained to allow the infant to spontaneously explore her breast. Initially, the mother refused to display the feeding pose potentially due to pain associated with breast engorgement. Massage was used to soften the breast and feeding was reintroduced. We hypothesize that activation of instinctive attachment formation mechanisms by encouraging spontaneity in each parent and child is the key to successful feeding intervention.

Here, we present a nonhuman primate model of mother-infant intervention for breastfeeding disorders in the presence of paternal inhibition and maternal neglect. The mate model video complements education to support primate and human caregivers with respect to infants with breastfeeding problems such as pain.

在存在父亲抑制和母亲忽视的情况下母婴干预母乳喂养障碍的常见狨猴模型

Parents&#39; psychological stress during the perinatal and neonatal periods continues to increase in an environment of declining birthrates, aging ...

行为学

Experimental Strategies to Bridge Large Tissue Gaps in the Injured Spinal Cord after Acute and Chronic Lesion

After a spinal cord injury (SCI) a scar forms in the lesion core which hinders axonal regeneration. Bridging the site of injury after an insult to the spinal cord, tumor resections, or tissue defects resulting from traumatic accidents can aid in facilitating general tissue repair as well as regenerative growth of nerve fibers into and beyond the affected area. Two experimental treatment strategies are presented: (1) implantation of a novel microconnector device into an acutely and completely transected thoracic rat spinal cord to readapt severed spinal cord tissue stumps, and (2) polyethylene glycol filling of the SCI site in chronically lesioned rats after scar resection. The chronic spinal cord lesion in this model is a complete spinal cord transection which was inflicted 5 weeks before treatment. Both methods have recently achieved very promising outcomes and promoted axonal regrowth, beneficial cellular invasion and functional improvements in rodent models of spinal cord injury.
The mechanical microconnector system (mMS) is a multi-channel system composed of polymethylmethacrylate (PMMA) with an outlet tubing system to apply negative pressure to the mMS lumen thus pulling the spinal cord stumps into the honeycomb-structured holes. After its implantation into the 1 mm tissue gap the tissue is sucked into the device. Furthermore, the inner walls of the mMS are microstructured for better tissue adhesion.
In the case of the chronic spinal cord injury approach, spinal cord tissue - including the scar-filled lesion area - is resected over an area of 4 mm in length. After the microsurgical scar resection the resulting cavity is filled with polyethylene glycol (PEG 600) which was found to provide an excellent substratum for cellular invasion, revascularization, axonal regeneration and even compact remyelination in vivo.

Severe spinal cord injuries often result in tissue defects. Two possibilities are described to successfully bridge such gaps to promote tissue adaptation, regenerative responses and functional improvement in rats via implantation of a mechanical microconnector system after acute injury and five weeks after complete spinal cord transection.

实验策略急，慢性损伤后桥的损伤脊髓组织大差距

After a spinal cord injury (SCI) a scar forms in the lesion core which hinders axonal regeneration. Bridging the site of injury after an insult to the ...

神经科学

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function

Mitochondrial dysfunction plays a significant role in the aging process and in neurodegenerative diseases including several hereditary spinocerebellar ataxias and other movement disorders marked by progressive degeneration of the cerebellum. The goal of this protocol is to assess mitochondrial dysfunction in Spinocerebellar ataxia type 1 (SCA1) and assess the efficacy of pharmacological targeting of metabolic respiration via the water-soluble compound succinic acid to slow disease progression. This approach is applicable to other cerebellar diseases and can be adapted to a host of water-soluble therapies.
Ex vivo analysis of mitochondrial respiration is used to detect and quantify disease-related changes in mitochondrial function. With genetic evidence (unpublished data) and proteomic evidence of mitochondrial dysfunction in the SCA1 mouse model, we evaluate the efficacy of treatment with the water-soluble metabolic booster succinic acid by dissolving this compound directly into the home cage drinking water. The ability of the drug to pass the blood brain barrier can be deduced using high performance liquid chromatography (HPLC). The efficacy of these compounds can then be tested using multiple behavioral paradigms including the accelerating rotarod, balance beam test and footprint analysis. Cytoarchitectural integrity of the cerebellum can be assessed using immunofluorescence assays that detect Purkinje cell nuclei and Purkinje cell dendrites and soma. These methods are robust techniques for determining mitochondrial dysfunction and the efficacy of treatment with water-soluble compounds in cerebellar neurodegenerative disease.

We present a biochemical and behavioral protocol to evaluate the efficacy of mitochondria-targeted water-soluble compounds for the treatment of Spinocerebellar ataxia type 1 (SCA1) and other cerebellar neurodegenerative diseases.

治疗SCA1小鼠水溶性化合物，以非特异性升压线粒体功能

Mitochondrial dysfunction plays a significant role in the aging process and in neurodegenerative diseases including several hereditary spinocerebellar ...

A Modified Murine Heterotopic Heart Transplant Protocol Matching Contemporary Standards of Aseptic Technique, Anesthesia, and Analgesia

The development of experimental models of cardiac transplantation in animals has contributed to many advances in the fields of immunology and solid organ transplantation. While the heterotopic vascularized murine cardiac transplantation model was initially utilized in studies of graft rejection using combinations of mismatched inbred mouse strains, access to genetically modified strains and therapeutic modalities can provide powerful new preclinical insights. Fundamentally, the surgical methodology for this technique has not changed since its development, especially with respect to important factors such as aseptic technique, anesthesia, and analgesia, which make material impacts on postsurgical morbidity and mortality. Additionally, improvements in perioperative management are expected to provide improvements in both animal welfare and experimental outcomes. This paper reports upon a protocol developed in collaboration with a subject matter expert in veterinary anesthesia and describes the surgical technique with an emphasis on perioperative management. Additionally, we discuss the implications of these refinements and provide details on troubleshooting critical surgical steps for this procedure.

The present paper describes a modified technique for heterotopic vascularized cardiac transplantation with updated aseptic technique, analgesia, and anesthesia.

符合当代无菌技术、麻醉和镇痛标准的改良小鼠异位心脏移植方案

The development of experimental models of cardiac transplantation in animals has contributed to many advances in the fields of immunology and solid organ ...

免疫与感染

A Model for Encephalomyosynangiosis Treatment after Middle Cerebral Artery Occlusion-Induced Stroke in Mice

There is no effective treatment available for most patients suffering with ischemic stroke, making development of novel therapeutics imperative. The brain's ability to self-heal after ischemic stroke is limited by inadequate blood supply in the impacted area. Encephalomyosynangiosis (EMS) is a neurosurgical procedure that achieves angiogenesis in patients with moyamoya disease. It involves craniotomy with placement of a vascular temporalis muscle graft on the ischemic brain surface. EMS has never been studied in the setting of acute ischemic stroke in mice. The hypothesis driving this study is that EMS enhances cerebral angiogenesis at the cortical surface surrounding the muscle graft. The protocol shown here describes the procedure and provides initial data supporting the feasibility and efficacy of the EMS approach. In this protocol, after 60 min of transient middle cerebral artery occlusion (MCAo), mice were randomized to either MCAo or MCAo + EMS treatment. The EMS was performed 3-4 h after occlusion. The mice were sacrificed 7 or 21 days after MCAo or MCAo + EMS treatment. Temporalis graft viability was measured using nicotinamide adenine dinucleotide reduced-tetrazolium reductase assay. A mouse angiogenesis array quantified angiogenic and neuromodulating protein expression. Immunohistochemistry was used to visualize graft bonding with brain cortex and change in vessel density. The preliminary data here suggest that grafted muscle remained viable 21 days after EMS. Immunostaining showed successful graft implantation and increase in vessel density near the muscle graft, indicating increased angiogenesis. Data show that EMS increases fibroblast growth factor (FGF) and decreases osteopontin levels after stroke. Additionally, EMS after stroke did not increase mortality suggesting that protocol is safe and reliable. This novel procedure is effective and well-tolerated and has the potential to provide information of novel interventions for enhanced angiogenesis after acute ischemic stroke.

The protocol aims to provide methods for encephalomyosynangiosis-grafting of a vascular temporalis muscle flap on the pial surface of ischemic brain tissue-for the treatment of non-moyamoya acute ischemic stroke. The approach's efficacy in increasing angiogenesis is evaluated using a transient middle cerebral artery occlusion model in mice.

小鼠脑中动脉闭塞诱导脑卒中后脑肌粘连血管病治疗模型

There is no effective treatment available for most patients suffering with ischemic stroke, making development of novel therapeutics imperative. The ...

大脑中动脉闭塞的短暂性脑缺血模型

Transient Middle Cerebral Artery Occlusion Model of Stroke

Stroke stands as a major cause of death or chronic disability globally. Nevertheless, existing optimal treatments are limited to reperfusion therapies during the acute phase of ischemic stroke. To gain insights into stroke physiopathology and develop innovative therapeutic approaches, in vivo rodent models of stroke play a fundamental role. The availability of genetically modified animals has particularly propelled the use of mice as experimental stroke models.
In stroke patients, occlusion of the middle cerebral artery (MCA) is a common occurrence. Consequently, the most prevalent experimental model involves intraluminal occlusion of the MCA, a minimally invasive technique that doesn't require craniectomy. This procedure involves inserting a monofilament through the external carotid artery (ECA) and advancing it through the internal carotid artery (ICA) until it reaches the branching point of the MCA. After a 45 min arterial occlusion, the monofilament is removed to allow reperfusion. Throughout the process, cerebral blood flow is monitored to confirm the reduction during occlusion and subsequent recovery upon reperfusion. Neurological and tissue outcomes are evaluated using behavioral tests and magnetic resonance imaging (MRI) studies.

作者聚焦:通过大脑中动脉闭塞模型评估缺血性卒中损伤 

This protocol describes the model of transient focal cerebral ischemia in mice through intraluminal occlusion of the middle cerebral artery. Additionally, examples of outcome assessment are shown using magnetic resonance imaging and behavioral tests.

脑卒中短暂性中动脉闭塞模型

Stroke stands as a major cause of death or chronic disability globally. Nevertheless, existing optimal treatments are limited to reperfusion therapies ...

开发用于狨猴精确神经记录的 x-y 电极台

Electrophysiology of Laminar Cortical Activity in the Common Marmoset

The marmoset monkey provides an ideal model for examining laminar cortical circuits due to its smooth cortical surface, which facilitates recordings with linear arrays. The marmoset has recently grown in popularity due to its similar neural functional organization to other primates and its technical advantages for recording and imaging. However, neurophysiology in this model poses some unique challenges due to the small size and lack of gyri as anatomical landmarks. Using custom-built micro-drives, researchers can manipulate linear array placement to sub-millimeter precision and reliably record at the same retinotopically targeted location across recording days. This protocol describes the step-by-step construction of the micro-drive positioning system and the neurophysiological recording technique with silicon linear electrode arrays. With precise control of electrode placement across recording sessions, researchers can easily traverse the cortex to identify areas of interest based on their retinotopic organization and the tuning properties of the recorded neurons. Further, using this laminar array electrode system, it is possible to apply a current source density analysis (CSD) to determine the recording depth of individual neurons. This protocol also demonstrates examples of laminar recordings, including spike waveforms isolated in Kilosort, which span multiple channels on the arrays.

作者聚焦:优化 Micro-Drive Systems 以实现 Marmoset 中的精确电极定位

Custom-built micro-drives enable the sub-millimeter targeting of cortical recording sites with linear silicon arrays.

普通狨猴层流皮层活动的电生理学

The marmoset monkey provides an ideal model for examining laminar cortical circuits due to its smooth cortical surface, which facilitates recordings with ...

氨甲环酸治疗消耗性狨猴综合征的改良及支持措施

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用改进的袖套法小鼠颈部心脏移植模型

在存在父亲抑制和母亲忽视的情况下母婴干预母乳喂养障碍的常见狨猴模型

实验策略急，慢性损伤后桥的损伤脊髓组织大差距

治疗SCA1小鼠水溶性化合物，以非特异性升压线粒体功能

符合当代无菌技术、麻醉和镇痛标准的改良小鼠异位心脏移植方案

小鼠脑中动脉闭塞诱导脑卒中后脑肌粘连血管病治疗模型

脑卒中短暂性中动脉闭塞模型

普通狨猴层流皮层活动的电生理学

脑卒中短暂性中动脉闭塞模型

脑卒中短暂性中动脉闭塞模型