重复震荡颅脑损伤模型小鼠
Summary
Concussion presents the most common type of traumatic brain injury. Therefore, a repetitive concussive animal model, which replicates the important features of an injury in patients, may provide a means to study concussion in a rigorous, controlled, and efficient manner.
Abstract
Despite the concussion/ mild traumatic brain injury (mTBI) being the most frequent occurrence of traumatic brain injury, there is still a lack of knowledge on the injury and its effects. To develop a better understanding of concussions, animals are often used because they provide a controlled, rigorous, and efficient model. Studies have adapted traditional animal models to perform mTBI to stimulate mild injury severity by changing the injury parameters. These models have been used because they can produce morphologically similar brain injuries to the clinical condition and provide a spectrum of injury severities. However, they are limited in their ability to present the identical features of injuries in patients. Using a traditional impact system, a repetitive concussive injury (rCHI) model can induce mild to moderate human-like concussion. The injury degree can be determined by measuring the period of loss of consciousness (LOC) with a sign of a transient termination of breathing. The rCHI model is beneficial to use for its accuracy and simplicity in determining mTBI effects and potential treatments.
Introduction
脑震荡，也被称为轻度颅脑损伤（MTBI），是创伤性脑损伤（TBI）的最频繁发生，影响数百万人在美国。震荡可能会非常棘手的诊断并没有为脑震荡没有具体的治疗。有越来越多的认可和一些证据表明，运动损伤，军事打击，以及其他物理引人入胜的追求导致轻微的机械性损伤可能有累积性，慢性神经后果1,2。然而，仍然有关于脑震荡及其影响的认识不足。现行方法限制病理和治疗的人类研究的，因为只有神经评估和成像评估可用于临床诊断。动物模型提供了学习的脑震荡与进一步的诊断和治疗MTBI的希望高效，严谨，可控的方式的一种手段。
有研究适应传统的TBI车型如控制皮质影响（CCI），液压冲击影响（FPI），体重下降损伤，爆炸伤执行MTBI通过改变参数的伤害低刺激伤害的严重性。这些模型，由于其复制脑外伤形态上类似于临床状况的能力是有益的使用;不过，他们也有自己的局限性。由加速度损伤（重量滴）诱导损伤的严重程度常常是高度可变的。轻度CCI的两种结果 – 蛛网膜下腔出血和挫伤焦点 – 不典型的脑震荡的人可比的。 CCI和FPI需要开颅手术，这不是临床相关，而爆伤是曝光3-6期间关于不同的曝光位置和峰值压力测量一个比较有争议的模型，以及可变继发性损伤。一个更新的震荡动物模型可以转化临床前研究的临床settiNG是必要的研究。
在模拟轻度TBI的关键问题是确定实验损伤严重，其中最密切复制在临床受伤。最近，不同的研究小组开发出闭合性颅脑损伤或震荡头部损伤（CHI）模型7-10。 CHI是CCI的不开颅的修改，但它依然采用的是传统的电子磁场影响系统产生头部撞击。阴气可以通过调节参数的影响引起了脑震荡，从轻度到中度。意识（LOC）的损失可立即通过检测呼吸速率或呼吸的瞬时终止的降低的冲击之后观察到。 LOC的期间被用于确定损伤的严重程度。本文包括小鼠重复CHI（rCHI）模型略有改善和更新版本，以及一个详细的一步一步的协议和代表的搜索结果。该rCHI模型研究战略重新确定MTBI效应和潜在的治疗有益的，特别是因为有能够模仿所有的脑震荡引起的病理变化没有个体动物模型。
Protocol
Representative Results
Discussion
模仿脑损伤形态相似的临床病症，预期脑震荡后症状。脑震荡的症状后一般包括头痛，头晕，眼花，乏力，记忆力和睡眠障碍，注意力无法集中以及焦虑，情绪低落。由于躯体症状可能还不是在动物模型衡量，运动和认知功能和情感行为的变化作为标准，在动物模型中合理评估脑震荡。在先前的报道的研究中，它表明，在rCHI小鼠模型诱导缺陷在空间学习，记忆和焦虑8。更重要的是，在此…
Divulgaciones
The authors have nothing to disclose.
Acknowledgements
This works was supported by funding from a Florida Health grant (Brain and spinal cord injury research fund) (KKW).
Materials
| anesthesia machine | Eagle Eye Anesthesia, Inc | Model 150 | anesthesia |
| Electromagnetic Impactor | LeicaBiosystems | Impact One Stereotaxic Impactor | perform impaction |
| Digital Stereotaxic instrument | LeicaBiosystems | 39462501 | mount mouse and positioning tips |
| Sicilone rubber-coated metal tip | Precision Tool & Engineering, Gainesvill FL | custom-made | impact tip |
| Lithium Ion All-in-One Trimmer | WAHL Home Products | 9854-600 | shave mouse hair |
| paper clips | custom-made | probe tip | |
| Cotton tipped applicators | MEDLINE | MDS202055 | scrub head with saline |
| Tissue Tek O.C.T. | ASKURA FINETEK USA INC | 4583 | tissue embedding |
| anti-GFAP | Dako | CA93013 | antibody for IHC |
| anti Ferritin | Sigma | F6136 | antibody for IHC |
| VECTASTAIN Elite ABC kit | Vector laboratories | PK-6100 | IHC detection system |
| Permount Mounting Medium | Fisher Scientific | SP15-100 | |
| Aperio XT ScanScope scanner | Leica Microsystems Inc, | slides scanning | |
| Leica AutoStainer XL | Leica the pathology Company | ST2010 | H&E staining |
| DAB | sigma | D3939 | IHC detection system |
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