| Surgical Induction of Endometriosis in Female Mice
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Author:
Date:
2020-09-20
[Abstract] Endometriosis is a common gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity. It is frequently associated with pain, infertility and a reduced quality of life, and it lacks adequate treatment. Several rodent models of endometriosis have been developed through heterologous and homologous transplantation of endometrial tissue into the abdominal compartment. Here we describe a surgical procedure to generate a syngeneic model of endometriosis in immunocompetent mice with intact uterine and ovarian tissues. In this model, four uterine fragments from a donor mouse at diestrus are sutured to the abdominal wall of a recipient mouse. One month after surgeries, endometrial implants develop into cysts with glandular epithelium and stroma, mimicking ...
[摘要] [摘要 ] 子宫内膜异位症是一种常见的妇科疾病，其特征是子宫腔外存在子宫内膜组织。它经常与疼痛，不育和生活质量下降有关，并且缺乏适当的治疗。子宫内膜异位症的几种啮齿动物模型是通过将子宫内膜组织异源和同源移植到腹腔中而开发的。在这里，我们描述了在具有完整子宫和卵巢组织的免疫功能小鼠中产生子宫内膜异位症的同基因模型的手术程序。在该模型中，将来自供体小鼠在二头肌的四个子宫碎片缝合到受体小鼠的腹壁上。手术一个月后，子宫内膜植入物发展成具有腺上皮和间质的囊肿，模仿了子宫内膜异位症女性中观察到的子宫内膜异位病变。因此，该小鼠模型为研究子宫内膜异位症的病理生理学和潜在治疗方法的有效性提供了有价值的工具。
[背景 ] 子宫内膜异位是由子宫外子宫内膜组织的生长所定义的一种慢性妇科疾病，主要在骨盆和腹部表面生长（Zondervan et al。，2018）。它影响了育龄妇女的10％，并且与疼痛，不孕症和生活质量下降有关（Fourquet 等人，2011;Márki 等人，2017; Zondervan 等人，2018）。子宫内膜异位症的可用药物和手术疗法具有不良作用，并且无法长期缓解症状（Falcone和Flyckt，2018年）。因此，需要新的治疗策略，其发展依赖于动物模型的建立，该模型概括了临床子宫内膜异位症的病理生理和行为特征。
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| Integration of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons into Rat Brain
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Author:
Date:
2020-09-05
[Abstract] Human neuron transplantation offers novel opportunities for modeling human neurologic diseases and potentially replacement therapies. However, the complex structure of the human cerebral cortex, which is organized in six layers with tightly interconnected excitatory and inhibitory neuronal networks, presents significant challenges for in vivo transplantation techniques to obtain a balanced, functional and homeostatically stable neuronal network. Here, we present a protocol to introduce human induced pluripotent stem cell (hiPSC)-derived neural progenitors to rat brains. Using this approach, hiPSC-derived neurons structurally integrate into the rat forebrain, exhibit electrophysiological characteristics, including firing, excitatory and inhibitory synaptic activity, and establish ...
[摘要] [摘要] 人类神经元移植为建模人类神经系统疾病和潜在的替代疗法提供了新的机会。然而，人脑皮层的复杂结构分为六层，具有紧密互连的兴奋性和抑制性神经元网络，这对体内移植技术获得平衡，功能稳定和稳态稳定的神经元网络提出了重大挑战。在这里，我们提出了一项协议，将人类诱导的多能干细胞（hiPSC ）衍生的神经祖细胞引入大鼠脑。使用这种方法，hiPSC 衍生的神经元在结构上整合到大鼠前脑中，表现出电生理特性，包括放电，兴奋性和抑制性突触活性，并与宿主电路建立神经元连通性。
[背景] 人类大脑皮层是一个复杂的细胞镶嵌体，在不同的皮质层（I-VI）中包含多样化的神经元亚型，可建立轴突输出和树突状输入的特定模式，提供了皮质电路的基本底物（Rakic，2009; Lodato 等等人，2011； Lui 等人，2011）。特别地，兴奋性和抑制性神经传递的平衡对于适当的脑功能是必需的（Turrigiano和Nelson，2004）。人类诱导的多能干细胞（hiPSC ）可以在人类遗传背景下对人类神经系统疾病进行建模（Dolmetsch和Geschwind，2011； Brennand 等，2015； Vera和Studer，2015）。建立体外系统以将hiPSCs ...
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| In vivo Blood-brain Barrier Permeability Assays Using Clostridium perfringens Epsilon Toxin
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Author:
Date:
2020-08-05
[Abstract] In order for the brain to function properly, a carefully orchestrated homeostasis must be maintained. To help regulate this delicate balance, the brain has developed a highly selective blood-brain barrier (BBB). Under normal conditions, the BBB excludes harmful blood-borne material from the brain parenchyma. However, numerous neuropathological conditions can disrupt this barrier, causing BBB permeability and subsequent CNS dysfunction. Understanding the mechanisms involved in BBB permeability are essential to elucidating the pathology of various neurological disorders as well as identifying methods for drug delivery to the CNS. Here, we describe several in vivo methods to measure BBB permeability in mice using an array of diverse sized tracers including exogenous 376 Da ...
[摘要] [摘要]为了使大脑正常工作，必须维持精心安排的体内平衡。为了帮助调节这种微妙的平衡，大脑已经形成了一种高度选择性的血脑屏障（BBB）。在正常情况下，血脑屏障将有害的血液传播物质排除在脑实质之外。然而，许多神经病理学条件可以破坏这一屏障，导致BBB通透性和随后的CNS功能障碍。了解BBB通透性的机制对于阐明各种神经系统疾病的病理学以及确定药物输送到中枢神经系统的方法至关重要。在这里，我们描述了几种在体内使用不同大小的示踪剂（包括外源性376da荧光素盐、66.5kDa牛血清白蛋白、70kDa右旋糖酐以及内源性160kDa小鼠IgG）来测量BBB在小鼠体内的通透性。当静脉注射时，这些物质会被BBB排除在健康大脑之外。然而，BBB功能障碍可使这些示踪剂进入大脑，这种积聚可通过分光光度法、荧光显微镜和免疫组织化学进行测量。我们还描述了一种利用产气荚膜梭菌epsilon毒素诱导BBB通透性的方法。最后，我们将简要讨论每种方法的优缺点及其适当的下游应用。
[背景] ...
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