Name: neurobehavioral assessments in a mouse model of neonatal hypoxic-ischemic brain injury
Uploaded: 2017-11-24T12:30:00.000+00:00
Duration: 8 min 32 s
Description: Watch this Scientific Journal Video about Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury at JoVE.com

这项研究得到了国家研究基金会 (NRF-2014R1A2A1A11052042; 2015M3A9B4067068)、大韩民国科学技术部、韩国健康技术研发 & 开发项目 (HI16C1012)、卫生部 & 的资助。福利, 大韩民国, 和世大学医学院的 "Dongwha" 教职员研究援助计划 (6-2016-0126)。

所有的动物都被安置在一个标准的笼子里 (27 x 22.5 x 14 厘米3) 在实验室动物保育协会 (AAALAC) 的认证和给予食物和水ad 随意在交替 12-h 光/暗周期.作者遵循动物保护条例, 实验程序由世大学医学院 (IACUC No. 2010-0252; 2013-0220) 机构动物保育和使用委员会批准。
1. 小鼠新生儿脑损伤模型
<ol><li>用异氟醚麻醉幼崽。<ol>
<li>将幼崽 (少于 5) 放入麻醉盒中, 并关上盖子。</li>
		<li>打开麻醉系统约15分钟;用台式麻醉机调节气体和异氟醚。调整氧气流量计为1.5 升/分, 调整的异氟醚蒸发器到3-5% 的诱导麻醉。</li>
		<li>15分钟后, 将异氟醚蒸发器调整到 1-2%, 用于麻醉的维护。</li>
	</ol>
</li>
	<li>在解剖显微镜下放置一个完全麻醉的幼崽 (面向研究员的腹部) 并用胶带固定。</li>
	<li>用消毒剪刀在颈部做一个0.7 毫米的切口。</li>
	<li>用灭菌钳将脂肪组织小心取出, 并暴露一侧右颈动脉。</li>
	<li>结扎5-0 可吸收缝合的单侧右颈动脉。</li>
	<li>用5-0 缝线缝合颈部的切口。</li>
	<li>将每只幼崽放在一个37° c 温暖的缺氧室中, 用于1小时的恢复。请勿关闭室盖。</li>
	<li>手术后1小时, 当幼崽完全清醒时, 关闭缺氧室盖, 降低气体水平以建立缺氧状态 (8% O2和 92% N2)。</li>
	<li>90分钟的缺氧后, 将幼崽返回笼子。</li>
	<li>脑损伤后一周, 重复步骤1。<ol>
<li>麻醉后, 用无菌剪刀和镊子在头皮上做一个切口, 以确定右半球后外侧的脑损伤。 注意: 这种疗法能诱导幼崽缺氧。所有小鼠脑损伤的存在和程度, 通过肉眼观察, 通过半透明的头骨进行目测评估。根据皮肤变色的大小或体积 (即脑部病变), 幼崽被分为组。如果没有明显的皮质损伤, 则将小鼠分为 "无皮质损伤" 组。如果有明显的皮质损伤 (即右半球的病灶), 则将小鼠分为 "皮质损伤" 组。由于对小鼠的分类是在手术后一周完成的, 所以当大脑样本的形态在牺牲时1、2、3中明确定义时, 可以对分组进行修改. 4。</li>
	</ol>
</li>
</ol><img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/55838/55838fig1v3.jpg"> 图 1: 对小鼠脑损伤进行建模。 (a) 一只七天大的小鼠接受了手术, 一侧右颈动脉结扎。(B) 幼崽被放在缺氧室中90分钟, 8% O2和 92% N2。(C、D 和 E)新生儿 HI 损伤的脑部表现出不同程度的损伤, 并根据损伤程度进行分类。在14周, 大脑得到了, 病变是可视化的。(C) 被归类为 "无皮质损伤" 的大脑的图像。(D) 和 (E) 分为 "皮质损伤" 组。(F、G 和 H)分别对 (C)、(D) 和 (E) 小鼠进行有代表性的 MRI 检查。(F) 海马的损伤用黄色箭头表示, 右半球的病灶也用黄色箭头 (G 和 H) 表示。缩放栏 = 1 mm<a href="http://cloudflare.jove.com/files/ftp_upload/55838/55838fig1v3large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
2. 新生儿行为测试
注意: 在这里, 行为测试是在6周的年龄进行的。
<ol><li>
被动回避任务。 注意: 为了评估基于学习和避免厌恶刺激的记忆功能, 两个隔间步进拍应进行13,14,15,16。<ol>
<li>将一只小鼠放入有机玻璃梭箱 (41.5 x 21 x 35 cm3) 的明亮车厢中。</li>
		<li>三十年代以后, 打开断头台门并且记录延迟时间为老鼠移动入黑暗的隔间 (由 300s)。</li>
		<li>关闭断头台门时, 所有的鼠标四四肢完全在黑暗的车厢内。</li>
		<li>管理电动脚休克 (0.5 毫安) 为2秒, 并将鼠标返回到它的笼子。</li>
		<li>在电动脚休克后, 在明亮的隔间中更换鼠标24小时。</li>
		<li>十年代把老鼠完全放在明亮的车厢里后打开断头台的大门, 并记录下鼠标进入黑暗车厢的等待时间 (高达 300s)。</li>
	</ol>
</li>
	<li>
阶梯行走试验。 注意: 阶梯梯级步行任务允许通过结合定性和定量分析熟练的步行17,18来区分运动功能的细微干扰。<ol>
<li>打开摄像机。</li>
		<li>将鼠标放在梯子的开始板上, 然后立即开始录制。</li>
		<li>录制视频, 重点放在鼠标的四肢。</li>
		<li>当鼠标触及梯子的最后一个面板时停止录制。重复来回旅行四次。</li>
		<li>分析视频记录, 并手动计算每个前肢的单张数, 如下所示:<ol>
<li>在计算机上以慢速 (0.1x) 播放视频记录, 并手动计算步骤。</li>
		</ol>
</li>
	</ol>
</li>
	<li>
握杆强度试验。 注: 握力测试采用握力计, 包括推拉式应变计。<ol>
<li>将握杆强度装置固定在压克力板上。</li>
		<li>将鼠标放在亚克力面板上, 并按住它的尾部。<ol>
<li>移动握着尾巴的手, 这样鼠标就能到达并握住仪器的金属线。</li>
		</ol>
</li>
		<li>允许多次试验, 直到鼠标握住三角形的金属丝 (直径2毫米);该仪器自动在克中登记峰值力。 注: 使用三试验的平均峰值力进行分析19,20,21。</li>
	</ol>
</li>
</ol>

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作者没有竞争利益。

在这项研究中, 我们诱发 HI 脑损伤的新生儿 P7-10 CD-1 小鼠, 并确定了脑损害的相关认知和运动缺陷。在这个过程中, 闭塞的单侧右颈动脉是至关重要的。在这一步, 动脉可能被破坏和撕裂。大多数经历过动脉撕裂的幼崽都死了。反之, 如果研究人员结扎了另一条血管而不是单侧右颈动脉, 小狗的大脑只轻度受损, 没有明显的表型可观察到24。
在这项研究中, 由于?...

新生儿 HI 脑损伤发生在幼儿期 (约两个病人每1000儿童)1,2,3,4,5。关于新生儿 hi 脑损伤的研究是重要的, 利用建立的新生儿脑损伤小鼠模型可以促进脑损伤的临床前期研究. 
传统的 HI 模型用于成年大鼠6。对于新生儿模型, Vannucci 法是常用的 P7 大鼠7,8。然而, 因为老鼠和老鼠是略有不同的9,10, 即使它们都是啮齿类动物, 我们在 P7-10 上对 CD-1 幼崽进行了改良的大米 Vannucci 方法, 根据先前的研究表明 P7-10 是未成熟的突, 对应于人类术语 P011,12。通过单侧颈动脉结扎和小鼠对 P7-10 幼犬缺氧8% 氧的暴露, 建立新生儿 HI 小鼠模型。
受手术影响的小鼠在右半球的后外侧区域显示出不同程度的脑损伤。为了识别认知和运动缺陷, 进行了基于 PAT、阶梯行走试验和握力测试的神经行为评估。分析了手术 (即正常) 和 HI 小鼠之间的差异。这项工作提供了关于 HI 鼠标模型的基本信息。MRI 图像显示不同的表型, 根据脑损害的严重性, 使用运动和认知测试分开。

<table><tbody><tr><td>Hypoxic chamber</td><td>Jeung Do Bio &amp;amp; Plant Co</td><td>Experimental Builder</td><td></td></tr><tr><td>PAT apparatus</td><td>Jeung Do Bio &amp;amp; Plant Co</td><td>Experimental Builder</td><td></td></tr><tr><td>The ladder rung walking</td><td>Jeung Do Bio &amp;amp; Plant Co</td><td>Experimental Builder</td><td></td></tr><tr><td>SDI Grip Strength System</td><td>San Diego Instruments Inc.</td><td></td><td></td></tr><tr><td>Grip-Strength Meter</td><td>Ugo Basile</td><td>47200</td><td></td></tr><tr><td>Harvard Apparatus Fluovac anesthetizing system&amp;nbsp;</td><td>Harvard Apparatus</td><td></td><td></td></tr><tr><td>Anesthetizing box</td><td></td><td></td><td>acryl box</td></tr><tr><td>I-Fran Liquid (Isofluorane)</td><td>Hana Pharm. Co., Ltd.</td><td></td><td>General Anesthetics ( isoflurane 100ml)</td></tr><tr><td>CD-1 mice</td><td>Orient Co., Ltd.</td><td></td><td></td></tr><tr><td>Blue Nylon Mono Non-Absorbbable suture 5-0 50cm</td><td>Ailee Co., Ltd.</td><td>NB 521</td><td></td></tr><tr><td>IBM SPSS Statistics</td><td>IBM</td><td>Ver. 23</td><td></td></tr></tbody></table>

neurobehavioral assessments in a mouse model of neonatal hypoxic-ischemic brain injury

我们对 CD-1 小鼠进行了单侧颈动脉闭塞, 以建立新生儿缺氧缺血 (hi) 模型, 并通过研究这些小鼠的神经行为功能与手术 (即:正常) 小鼠。在这项研究中, Vannucci 的方法被用来诱导新生儿脑损伤在产后7-10 天 (P7-10) 小鼠。通过单侧颈动脉结扎和暴露于缺氧 (8% O2和 92% N2为 90 min) 对幼犬进行 HI 操作。手术后一周, 受损的大脑用肉眼通过半透明的头骨进行评估, 并根据缺席 ("无皮质损伤" 组) 或皮质损伤的存在 ("皮质损伤" 组) 进行分组。比如右半球的病灶在6周, 进行了以下神经行为测试, 以评估认知和运动功能: 被动回避任务 (PAT), 阶梯行走试验和握力测试。这些行为测试有助于确定新生儿 HI 脑损伤的影响, 并用于其他神经退行性疾病的小鼠模型。在这项研究中, 新生的 HI 脑损伤小鼠显示出与右半球损伤相对应的运动缺陷。行为测试结果与人类新生儿脑瘫或新生儿中风患者出现的缺陷有关。在这项研究中, 建立了一个小鼠脑损伤模型, 并显示了不同程度的运动缺陷和认知障碍相比, 手术的老鼠。这项工作提供了关于 HI 鼠标模型的基本信息。MRI 图像显示不同的表型, 根据严重的大脑损伤的运动和认知测试分开。

所有数据都被表示为平均±标准误差 (SEM)。通过对 SPSS 统计软件进行独立或配对的t测试, 对两个组之间的变量进行比较。p值 < 0.05 被认为具有统计学意义。
新生儿 HI 损伤的大脑表现出不同程度的损伤, 并据此分类 (图 1C-E)。大脑是在14周获得的, 病变是可视化的。图 1C显...

Watch this Scientific Journal Video about Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury at JoVE.com

Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury

我们进行了单侧颈动脉闭塞产后 7-10 CD-1 小鼠幼崽创建一个新生儿缺氧缺血 (hi) 模型和调查的影响, hi 脑损伤。我们研究了这些小鼠的神经行为功能与手术正常小鼠相比。

小鼠新生儿缺氧缺血性脑损伤模型的神经行为评估

We performed unilateral carotid artery occlusion on CD-1 mice to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of neonatal HI ...

neurobehavioral-assessments-mouse-model-neonatal-hypoxic-ischemic

Research

JoVE Journal

Neuroscience

12.2K 次观看.  Yonsei University College of Medicine. 我们进行了单侧颈动脉闭塞产后 7-10 CD-1 小鼠幼崽创建一个新生儿缺氧缺血 (hi) 模型和调查的影响, hi 脑损伤。我们研究了这些小鼠的神经行为功能与手术正常小鼠相比。

视频: Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury

Mouse Models of Periventricular Leukomalacia

We describe a protocol for establishing mouse models of periventricular leukomalacia (PVL). PVL is the predominant form of brain injury in premature infants and the most common antecedent of cerebral palsy. PVL is characterized by periventricular white matter damage with prominent oligodendroglial injury. Hypoxia/ischemia with or without systemic infection/inflammation are the primary causes of PVL. We use P6 mice to create models of neonatal brain injury by the induction of hypoxia/ischemia with or without systemic infection/inflammation with unilateral carotid ligation followed by exposure to hypoxia with or without injection of the endotoxin lipopolysaccharide (LPS). Immunohistochemistry of myelin basic protein (MBP) or O1 and electron microscopic examination show prominent myelin loss in cerebral white matter with additional damage to the hippocampus and thalamus. Establishment of mouse models of PVL will greatly facilitate the study of disease pathogenesis using available transgenic mouse strains, conduction of drug trials in a relatively high throughput manner to identify candidate therapeutic agents, and testing of stem cell transplantation using immunodeficiency mouse strains.

We established mouse models of periventricular leukomalacia (PVL), the predominant brain injury in premature infants characterized by periventricular white matter lesions. Hypoxia/ischemia with/without systemic infection are the primary causes of PVL. Unilateral carotid ligation and hypoxia exposure with/without lipopolysaccharide injection creates PVL-like lesions in P6 mice.

脑室周围白质软化的小鼠模型

We describe a protocol for establishing mouse models of periventricular leukomalacia (PVL). PVL is the predominant form of brain injury in premature ...

科研

神经科学

Neurodevelopmental Reflex Testing in Neonatal Rat Pups

Neurodevelopmental reflex testing is commonly used in clinical practice to assess the maturation of the nervous system. Neurodevelopmental reflexes are also referred to as primitive reflexes. They are sensitive and consistent with later outcomes. Abnormal reflexes are described as an absence, persistence, reappearance, or latency of reflexes, which are predictive indices of infants that are at high risk for neurodevelopmental disorders. Animal models of neurodevelopmental disabilities, such as cerebral palsy, often display aberrant developmental reflexes, as would be observed in human infants. The techniques described assess a variety of neurodevelopmental reflexes in neonatal rats. Neurodevelopmental reflex testing offers the investigator a testing method that is not otherwise available in such young animals. The methodology presented here aims to assist investigators in examining developmental milestones in neonatal rats as a method of detecting early-onset brain injury and/or determining the effectiveness of therapeutic interventions. The methodology presented here aims to provide a general guideline for investigators.

Behavioral testing is the gold standard for determining outcomes following brain injury, and can identify the presence of developmental disabilities in infants and children. Neurodevelopmental reflexes are an early indicator of these abnormalities. A host of easily accomplished developmental reflex tests in the neonatal rodent were developed and described here.

神经发育复检新生幼鼠

Neurodevelopmental reflex testing is commonly used in clinical practice to assess the maturation of the nervous system. Neurodevelopmental reflexes are ...

行为学

The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia

Hypoxic-Ischemic Encephalopathy (HIE) is the consequence of systemic asphyxia occurring at birth. Twenty five percent of neonates with HIE develop severe and permanent neuropsychological sequelae, including mental retardation, cerebral palsy, and epilepsy. The outcomes of HIE are devastating and permanent, making it critical to identify and develop therapeutic strategies to reduce brain injury in newborns with HIE. To that end, the neonatal rat model for hypoxic-ischemic brain injury has been developed to model this human condition. The HIE model was first validated by Vannucci et al 1 and has since been extensively used to identify mechanisms of brain injury resulting from perinatal hypoxia-ischemia 2 and to test potential therapeutic interventions 3,4. The HIE model is a two step process and involves the ligation of the left common carotid artery followed by exposure to a hypoxic environment. Cerebral blood flow (CBF) in the hemisphere ipsilateral to the ligated carotid artery does not decrease because of the collateral blood flow via the circle of Willis; however with lower oxygen tension, the CBF in the ipsilateral hemisphere decreases significantly and results in unilateral ischemic injury. The use of 2,3,5-triphenyltetrazolium chloride (TTC) to stain and identify ischemic brain tissue was originally developed for adult models of rodent cerebral ischemia 5, and is used to evaluate the extent of cerebral infarctin at early time points up to 72 hours after the ischemic event 6. In this video, we demonstrate the hypoxic-ischemic injury model in postnatal rat brain and the evaluation of the infarct size using TTC staining.

The postnatal rat model for hypoxic-ischemic brain injury is a well-established model of human neonatal hypoxic ischemic encephalopathy (HIE). In this article, we describe the model of HIE in post-natal rat pups.

围产期缺血缺氧缺血性脑病模型

Hypoxic-Ischemic Encephalopathy (HIE) is the consequence of systemic asphyxia occurring at birth. Twenty five percent of neonates with HIE develop severe ...

生物学

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world&#8217;s 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials1,2. The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (&#60; 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.

Hypoxic-ischemic encephalopathy following perinatal asphyxia can be studied using animal models. We demonstrate the procedures necessary for establishing a piglet model of neonatal hypoxic-ischemic encephalopathy.

新生儿缺氧缺血性脑病的小猪模型

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the ...

医学

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders

Induction of phosphorylated extracellular-regulated kinase (pERK) is a reliable molecular readout of learning-dependent neuronal activation. Here, we describe a pERK immunohistochemistry protocol to study the profile of hippocampal neuron activation following exposure to a spatial learning task in a mouse model characterized by cognitive deficits of neurodevelopmental origin. Specifically, we used pERK immunostaining to study neuronal activation following Morris water maze (MWM, a classical hippocampal-dependent learning task) in Engrailed-2 knockout (En2-/-) mice, a model of autism spectrum disorders (ASD). As compared to wild-type (WT) controls, En2-/- mice showed significant spatial learning deficits in the MWM. After MWM, significant differences in the number of pERK-positive neurons were detected in specific hippocampal subfields of En2-/- mice, as compared to WT animals. Thus, our protocol can robustly detect differences in pERK-positive neurons associated to hippocampal-dependent learning impairment in a mouse model of ASD. More generally, our protocol can be applied to investigate the profile of hippocampal neuron activation in both genetic or pharmacological mouse models characterized by cognitive deficits.

We describe an immunohistochemistry protocol to study the profile of hippocampal neuron activation following exposure to a spatial learning task in a mouse model characterized by cognitive deficits of neurodevelopmental origin. This protocol can be applied to both genetic or pharmacological mouse models characterized by cognitive deficits.

海马神经元活动的可视化免疫组化空间后学习神经发育障碍的小鼠模型

Induction of phosphorylated extracellular-regulated kinase (pERK) is a reliable molecular readout of learning-dependent neuronal activation. Here, we ...

A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy

As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, standardized battery of neonatal mouse motor tests. These tests can validate injury or disease models, determine treatment efficacy and/or assess motor behaviors in new transgenic strains. This paper presents a series of neonatal motor tests to evaluate general motor function, including ambulation, hindlimb foot angle, surface righting, negative geotaxis, front- and hindlimb suspension, grasping reflex, four limb grip strength and cliff aversion. Mice between the ages of post-natal day 2 to 14 can be used. In addition, these tests can be used for a wide range of neurological and neuromuscular pathologies, including cerebral palsy, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, neurodegenerative diseases, and neuromuscular disorders. These tests can also be used to determine the effects of pharmacological agents, as well as other types of therapeutic interventions. In this paper, motor deficits were evaluated in a novel neonatal mouse model of cerebral palsy that combines hypoxia, ischemia and inflammation. Forty-eight hours after injury, five tests out of the nine showed significant motor deficits: ambulation, hindlimb angle, hindlimb suspension, four limb grip strength, and grasping reflex. These tests revealed weakness in the hindlimbs, as well as fine motor skills such as grasping, which are similar to the motor deficits seen in human cerebral palsy patients.

Presented is a concise battery of mouse neonatal motor tests. Using these tests, neonatal motor deficits can be demonstrated in a variety of neonatal motor disorders. By having a standardized set of tests, results from different studies can be compared, allowing for better and accurate reporting between groups.

汽车测试的脑瘫新生儿小鼠模型电池

As the sheer number of transgenic mice strains grow and rodent models of pediatric disease increase, there is an expanding need for a comprehensive, ...

A Controlled Mouse Model for Neonatal Polymicrobial Sepsis

Neonatal sepsis remains a global burden. A preclinical model to screen effective prophylactic or therapeutic interventions is needed. Neonatal mouse polymicrobial sepsis can be induced by injecting cecal slurry intraperitoneally into day of life 7 mice and monitoring them for the following week. Presented here are the detailed steps necessary for the implementation of this neonatal sepsis model. This includes making a homogeneous cecal slurry stock, diluting it to a weight- and litter-adjusted dose, an outline of the monitoring schedule, and a definition of observed health categories used to define humane endpoints. The generation of a homogeneous cecal slurry stock from pooled donors allows for the administration into many litters over time, reducing the variation between donors, and preventing the use of potentially toxic glycerol. The monitoring strategy used allows for the anticipation of survival outcome and the identification of mice that would later progress to death, allowing for an earlier identification of the humane endpoint. Two main behavioral features are used to define the health scores, namely, the ability of the neonatal mice to right themselves when placed on their back and their level of mobility. These criteria could potentially be applied to address humane endpoints in other studies of neonatal disease in mice, as long as a pilot study is performed to confirm accuracy. In conclusion, this approach provides a standardized method to model newborn sepsis in mice, while providing resources to assess animal welfare used to define early humane endpoints for challenged animals.

This protocol provides the necessary steps to establish and evaluate neonatal sepsis in 7-day-old mice.

新生儿多药脓毒症的对照小鼠模型

Neonatal sepsis remains a global burden. A preclinical model to screen effective prophylactic or therapeutic interventions is needed. Neonatal mouse ...

免疫与感染

Continuous Video Electroencephalogram during Hypoxia-Ischemia in Neonatal Mice

Hypoxia ischemia is the most common cause of neonatal seizures. Animal models are crucial for understanding the mechanisms and physiology underlying neonatal seizures and hypoxia ischemia. This manuscript describes a method for continuous video electroencephalogram (EEG) monitoring in neonatal mice to detect seizures and analyze EEG background during hypoxia ischemia. Use of video and EEG in conjunction allows description of seizure semiology and confirmation of seizures. This method also allows analysis of power spectrograms and EEG background pattern trends over the experimental time period. In this hypoxia ischemia model, the method allows EEG recording prior to injury to obtain a normative baseline and during injury and recovery. Total monitoring time is limited by the inability to separate pups from the mother for longer than four hours. Although, we have used a model of hypoxic-ischemic seizures in this manuscript, this method for neonatal video EEG monitoring could be applied to diverse disease and seizure models in rodents.

This manuscript describes a method for continuous video EEG recordings using multiple depth electrodes in neonatal mice undergoing hypoxia-ischemia.

新生小鼠缺氧缺血期间的连续视频脑电图

Hypoxia ischemia is the most common cause of neonatal seizures. Animal models are crucial for understanding the mechanisms and physiology underlying ...

Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy

Perinatal hypoxic-ischemic encephalopathy (HIE) is an acute disease that may afflict newborns, resulting in variable long- and short-term neurodevelopmental outcomes. Early diagnosis is critical to identifying infants who may benefit from intervention; however, early diagnosis relies heavily on clinical criteria. No molecular or radiological tests have shown promise in detecting early cerebral injury. Studies have shown that magnetic resonance imaging (MRI) can show changes in both blood flow/ischemia and metabolic disruption. However, they have all been used to evaluate the secondary phase of the disease (&gt;12 h) after the onset of the injury. Early diagnosis is critical to rapidly starting therapeutic hypothermia in eligible infants, which is currently recommended to be initiated within 6 h of birth. The rat model of hypoxic-ischemic injury was developed in 1981 and has been validated and used extensively to study changes in brain perfusion, cerebral injury markers, and morphology. However, it has primarily been used as a "late model", evaluating injury several days after the initial ischemic insult. The model has been known to have poor sensitivity in evaluating reliable and reproducible early cerebral changes. The objective of this study was to develop a reliable model to study early gross morphological and radiological markers of HIE using pathological staining and cerebral magnetic resonance imaging/magnetic resonance spectroscopy.

The present protocol describes a rodent model of newborn hypoxic-ischemic injury for identifying early changes in cerebral tissue by gross morphology and magnetic resonance imaging. This has benefits over existing models, which can be used to study late injury but do not allow the evaluation of reproducible early changes.

Perinatal hypoxic-ischemic encephalopathy (HIE) is an acute disease that may afflict newborns, resulting in variable long- and short-term ...

<meta charset="utf8"></head><body>CHILD 模型 — 回顾小鼠的青少年脑震荡和长期结果

A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)

Concussions and mild traumatic brain injuries (mTBI) during childhood represent a significant health endangerment, with many patients later in life exhibiting debilitating physiological, neurological, and psychosocial outcomes. The cellular and molecular pathophysiological mechanisms are relatively unknown, and this significant gap effectively precludes investigations into specific therapeutic strategies to mitigate chronic sequelae. No single animal concussion model recapitulates all the features reported in human subjects, and current models are designed to answer specific research questions. We set out to develop a juvenile concussion that recapitulates clinical early, and long-term symptomology encountered, termed Closed Head Injury with Long-term Disorder (CHILD). In this model, a concussive force via an electromagnetic impactor is delivered to the head of a lightly anesthetized unrestrained post-natal day 17 (P17) mouse, allowing free rotation of the head. Mice are placed on a tightly stretched tin foil across a stereotactic device, and the impactor is carefully aligned with the targeted cortical region. The electromagnetic impactor facilitates the selection of impact depth, dwell, and duration to determine injury severity. A strength of this model is that it allows head rotation, an important clinical feature. After impact, mice are immediately monitored for righting time and time to explore their environment, followed by their return to their dam. Increasing the severity of concussion results in intracranial bleeds in a subset of mice. Mice can be routinely monitored for behavior and neuroimaging over their lifespan, as desired. Various injury severities mimic the heterogeneous nature of juvenile concussions. The current standard CHILD model exhibits no skull fracture, no observable conventional neuroimaging change (similar to clinical), but leads to progressive and persistent neuronal death, altered diffusion MRI, modified neuronal activity and plasticity, increased gliosis, and progressive behavioral perturbations with age. In summary, this CHILD model mimics the early and long-term features observed in many clinical concussion patients.

<meta charset="utf8"></head><body>小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病 （CHILD）

Pediatric concussions can result in long-term sequelae with physiological and psychological perturbations. This pediatric concussion mouse model results in long-term neuroinflammation, white matter alterations, and neuronal modifications with behavioral dysfunction. The model can be adapted to differential impact locations or repeated concussions to assess lifetime changes.

小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病 （CHILD） 

Concussions and mild traumatic brain injuries (mTBI) during childhood represent a significant health endangerment, with many patients later in life ...

小鼠新生儿缺氧缺血性脑损伤模型的神经行为评估

摘要

探索更多视频

此视频中的章节

脑室周围白质软化的小鼠模型

神经发育复检新生幼鼠

围产期缺血缺氧缺血性脑病模型

新生儿缺氧缺血性脑病的小猪模型

海马神经元活动的可视化免疫组化空间后学习神经发育障碍的小鼠模型

汽车测试的脑瘫新生儿小鼠模型电池

新生儿多药脓毒症的对照小鼠模型

新生小鼠缺氧缺血期间的连续视频脑电图

Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy

小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病（CHILD）

小鼠新生儿缺氧缺血性脑损伤模型的神经行为评估

摘要

探索更多视频

此视频中的章节

脑室周围白质软化的小鼠模型

神经发育复检新生幼鼠

围产期缺血缺氧缺血性脑病模型

新生儿缺氧缺血性脑病的小猪模型

海马神经元活动的可视化免疫组化空间后学习神经发育障碍的小鼠模型

汽车测试的脑瘫新生儿小鼠模型电池

新生儿多药脓毒症的对照小鼠模型

新生小鼠缺氧缺血期间的连续视频脑电图

Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy

小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病 （CHILD）

小鼠儿科脑震荡模型:闭合性颅脑损伤伴长期疾病（CHILD）