我们感谢伊恩粗的帮助与外科准备的主题和伊丽莎白, 她精心编辑。这些研究已经完成, 作为一个团队的一部分, 由穆迪的转化性颅脑损伤研究项目资助。

<ol>
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L., Capra, B., Eidson, K., Garcia, J., Kennedy, D., Uchida, T., 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=Dose-dependent+neuronal+injury+after+traumatic+brain+injury.">Dose-dependent neuronal injury after traumatic brain injury.</a> Brain Research. 1044, 144-154 (2005).</li><li>Bramlett, H. M., Detrich, W. 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+consequences+of+Traumatic+Brain+Injury:+Current+Status+of+Potential+Mechanisms+of+Injury+and+Neurological+Outcomes.">Long-Term consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes.</a> J. Neurotrauma. 32, 1-15 (2015).</li><li>Pierce, J. E. S., Smith, D. H., Trojanowski, J. Q., McIntosh, T. 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Y., Yu, W., Weinberg, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Circadian+phase+and+sex+effects+on+depressive/anxiety-like+behaviors+and+HPA+axis+responses+to+acute+stress.">Circadian phase and sex effects on depressive/anxiety-like behaviors and HPA axis responses to acute stress.</a> Physiol Behav. 99, 276-285 (2010).</li><li>Schallert, T., Woodlee, M. T., Fleming, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+Focal+Ischemic+Injury:+Behavior-Brain+Interactions+and+Issues+of+Animal+Handling+and+Housing.">Experimental Focal Ischemic Injury: Behavior-Brain Interactions and Issues of Animal Handling and Housing.</a> ILAR J. 44 (2), 130-143 (2003).</li><li>Ruis, J. F., Rietveld, W. J., Buys, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Properties+of+parametric+photic+entrainment+of+circadian+rhythms+in+the+rat.">Properties of parametric photic entrainment of circadian rhythms in the rat.</a> Physiol Behav. 50, 1233-1239 (1991).</li><li>Ferguson, S. A., Maier, K. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+review+of+seasonal/circannual+effects+of+laboratory+rodent+behavior.">A review of seasonal/circannual effects of laboratory rodent behavior.</a> Physiol Behav. 119, 130-136 (2003).</li><li>Fujimoto, S. T., Longhi, L., Saatman, K. E., McIntosh, T. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+and+cognitive+function+evaluation+following+experimental+traumatic+brain+injury.">Motor and cognitive function evaluation following experimental traumatic brain injury.</a> Neurosci &amp; Biobehav Reviews. , (2004).</li><li>Gold, E. M., Su, D., Lopez-Velazquez, L., Haus, D. L., Perez, H., Lacuesta, G. A., Anderson, A. J., Cummings, B. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+assessment+of+long-term+deficits+in+rodent+models+of+traumatic+brain+injury.">Functional assessment of long-term deficits in rodent models of traumatic brain injury.</a> Regen. Med. 8 (4), 483-516 (2013).</li></ol>

作者没有什么可透露的。

在进行任何类型的行为测试时, 保持一致是至关重要的。这个细节包括许多看似微不足道但对动物的反应有重大影响的考虑。一个不容忽视的重要步骤是, 在进行任何实验之前, 动物都要适应他们的家笼/住房状况。这种准备减少动物的生理应激反应的影响, 这可以改变行为的结果18。同样, 必须尽一切努力以同样的方式处理所有的动物。这种一致性包括, 如前所述, 适应住房, 也适应处理和交通之间的训练或测试前的房间。这个概念不能被夸大。草率的动物处理是灾难性的任何行为测试19。同样, 无论是在黑暗中还是在光周期中, 都需要在一天的同一时间对动物进行测试。对于此处讨论的测试, 在光照或暗阶段进行测试是可以接受的, 只要测试是一致执行的。在昼夜节律周期的不同时间进行的测试已经被证明可以改变行为结果18,20。此外, 处理程序以及动物必须在一个压力释放, 平静的状态, 以最大限度地提高结果的准确性。
特别是在 Neuroscore 的情况下, 假阳性和阴性是共同的。假阳性通常发生在动物没有完全习惯于处理和测试。动物必须完全放松, 所以观察到的反应是反身的, 而不是由于肌肉收紧而引起的压力或恐惧。紧张的处理可以通过向动物传递压力来影响结果。因此, 把老鼠抓得太紧或太松都可能会有问题。另外, 如果处理程序是紧张的, 这可能混淆老鼠的反应。还有一个风险, 没有经验的观察家会曲解老鼠的反应。良好的训练和大量的练习对 Neuroscore 的成功和一致性至关重要。
总的来说, 这些测试的主要关注点在于治疗组之间缺乏很大的差异, 有时也没有区别。由于动物对不同的处理程序、噪音、时间以及可能的季节21有不同的反应, 所以必须尽力减少所有可能的混杂因素。
在这里显示的平衡木平衡和束流任务的结果表明, 这些测试是有用的早期损伤后, 发现缺陷的 vestibulomotor 功能。这些缺陷通常会随着时间的推移而解决1,14。在这个模型中, 受伤后6月, 损伤引起的赤字已经解决。6月时间点的结果表明, 天真、虚伪或受伤的老鼠之间没有区别;然而, 所有的老鼠都在自家笼子里放松了6月, 变老, 发胖了。因此, 当他们在6月后的手术中重新测试 (或在幼稚的情况下是等价的), 他们基本上是变老和脂肪, 因此, 所有的组不执行, 以及他们相比, 他们的基线日0的结果。
另一个重要的考虑是, 使用的行为测试是正确的测试。例如, 这里使用的测试被认为代表了特定大脑区域的功能。一个例子是前庭系统, 这是重要的平衡。涉及运动功能的脑区, 如皮层包括运动皮质、丘脑、脊髓神经元、基底神经节、nigro 纹状体等, 都参与了 vestibulomotor 的协调。因此, 平衡木平衡或束流中的赤字表明了这些地区的潜在赤字。此外, 海马和前额叶皮层参与了由工作记忆水迷宫测试的学习记忆功能。即使选择了正确的测试, 也必须牢记所使用的测试的局限性。例如, 这里所提供的任何测试都不敏感于情绪上的缺陷, 如抑郁、焦虑或社会互动, 如侵略、决策或冲动。要重申, 必须选择适当的测试, 对行为和大脑区域进行评估。
必须谨慎地对待行为数据的解释和分析。强烈建议对每种类型的测试分别进行功率分析, 因为, 使用行为结果作为神经缺陷的量度, 是由于它的性质, 是一种微妙的影响的粗略量度。此外, 不同的测试需要不同类型的统计分析。例如, 所描述的 Neuroscore 和平衡木平衡测试依赖于对训练有素的观察者的解释, 用序号刻度来评分行为。这些类型的数据不是连续的, 也不是正态分布的, 所以应该使用非参数统计, 如克鲁斯卡尔-瓦利斯测试, 如6.1 和6.2 节所示。另外, 波束行走和工作记忆的水迷宫测试产生的数据是连续的和正常分布的, 所以参数统计可以使用, 如单向方差分析或重复测量的双向方差分析, 如6.3 和6.4 节所示。
这里提出的行为任务经受了时间的考验, 并给出了重现性的结果, 特别是当与大鼠的外国证券投资模型配对时, 尽管许多其他的脑损伤行为测试方法确实存在。neuroscore 是用最少的设备进行的简短评估。其他的反射和强度测试可用, 并可纳入神经评估, 如横向 pulsion 任务, 不能试验, 斜面试验, 握力 (见藤本et al.22和金色et al.23). 所描述的平衡木平衡和光束行走任务是损伤后 vestibulomotor 的测量。Vestibulomotor 的协调可以被认为是一个衡量的总运动行为, 而其他措施的总活动赤字包括 Rotarod, 旋转极, 和开放的野外行动。游泳的能力, 测量作为游泳速度在水迷宫期间, 也是总马达协调的征兆22,23。工作记忆水迷宫任务通过检测两个参考内存赤字 (由试验1表示) 和工作记忆缺陷 (由试验2或试验1和试验2之间的差异) 来完成这套测试。认知功能的其他措施包括八臂径向迷宫, 巴恩斯迷宫, 新的物体识别测试, 以及不同的水迷宫的变化。这些变化包括原始的莫里斯水迷宫和拉什利 III 迷宫 (再看见藤本et al.22和金色et al.23). 这一电池的测试证明是有用的早期损伤后, 并在不同程度上, 12 月后受伤的1。
此外, 在这里演示的任务可以用于不同的菌株, 性别, 和年龄的大鼠;然而, 住宿可能需要为不同的大小和在更大的弱点的情况下作出。例如, 较年长、较重的老鼠需要更宽的光束来进行平衡木平衡任务, 而年老、体弱的老鼠, 在水迷宫中可能需要更短的游泳时间。因此, 在这些测试中有灵活的余地, 并且有可能开发新的测试以适应不同的情况和假设。

本文所提出的方法是为了检测大鼠脑外伤实验模型诱发的大脑特定区域的功能缺损。四不同的行为测试将被描述。首先, 短神经学评估, 称为 neuroscore, 可以在不需要任何专门设备的情况下进行, 但需要实践;这个测试检测反射的缺陷。其次, 平衡木平衡测试检测到平衡能力的缺陷。此任务要求处理程序根据序号比例对 rat 进行评分, 并需要对处理程序进行一些培训。平衡木平衡测试需要一个狭窄的光束, 并且对前庭系统的缺陷很敏感。第三个测试评估 vestibulomotor 协调。这项试验被称为 "波束行走" 任务, 虽然需要对大鼠进行一些预训练, 但这一过程比前两种方法更客观, 因为通过光束的潜伏期是不依赖于主观评分的客观措施。这种差异是因为测量了穿过窄光束到达一个安全箱的时间。光束行走试验需要比光束平衡更长的光束, 以及一个逃生箱。这项测试测量两种运动协调和平衡的缺陷, 因此对小脑和与运动神经相关的脑区的损伤敏感。工作记忆版本的莫里斯水迷宫 (MWM-WM) 主要测试海马功能和与前额叶皮质或执行功能的整合。所示的莫里斯水迷宫的版本也可以用来检测参考内存中的缺陷1。
这些方法是根据他们在文献中建立的良好记录而选择的。每一个都是有效的, 从不同的实验室与多个品系的大鼠在许多年的研究。然而, 在过去, 受伤后长达两周的伤害措施被认为是 "慢性" 时间点。因此, 为研究鼠脑外伤的慢性影响, 建立行为技术, 这些众所周知的方法需要评估灵敏度, 以检测损伤后较长时间点的创伤后诱发缺损。目前已有几种啮齿类动物模型, 该模型是应用最广泛的一种, 并在本研究中得到运用。此模型在1950的2中首次发布, 此后, 超过1000篇论文在大鼠中使用了 "3"。这种类型的伤害的神经病已经很好地描述了我们的4和其他5,6,7。简言之, 在损伤后的短时间内, 海马神经元的损伤表现为剂量依赖性,即, 24-48 小时;虽然严重萎缩和空化包括内囊和皮质的变薄, 在受伤后一年报告6,7。
大脑功能的最有意义的表现是通过在实验性脑损伤后使用行为结果测量来评估的。然而, 绝大多数的外国证券投资试验使用行为的结果, 使措施相对较早, 通常从1到14天后受伤。使用此处演示的方法, 某些行为缺陷可以在损伤后12月内检测到1。神经功能, 总 vestibulomotor 功能, 和精细运动协调评估后受伤天数 (pid) 1-3 和在 3, 6, 和12月后, 手术, 使用短期神经评估 (Neuroscore; 从 Schallert 修改8),平衡木平衡任务, 和光束遍历任务9,10,11。参考和工作记忆使用的工作记忆版本的莫里斯水迷宫1,12,13。

<table>
	<tbody>
		<tr>
			<td>Sprague-Dawley rats</td>
			<td>Charles Rivers Laboratories 
			251 Ballardvale St 
			Wilmington, MA 01887-1096 
			Phone: 800-522-7287</td>
			<td>CD-IGS rats, strain code 001</td>
			<td>male, albino, 300-350g at arrival</td>
		</tr>
		<tr>
			<td>Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Beam-Balance</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Beam</td>
			<td>home built</td>
			<td></td>
			<td>wood, 25&#34; l x 1&#34; h x 3/4&#34; w sealed with polyurethane varnish</td>
		</tr>
		<tr>
			<td>C-clamp</td>
			<td>Home Depot</td>
			<td>1422-C</td>
			<td>2 1/2&#34;</td>
		</tr>
		<tr>
			<td>barrier</td>
			<td>Home Depot</td>
			<td></td>
			<td>styrofoam, 18&#34; x 17 1/2&#34;</td>
		</tr>
		<tr>
			<td>table (for both BB &#38; BW)</td>
			<td>generic office supply</td>
			<td></td>
			<td>37&#34; h x 30&#34; w x 60&#34; l</td>
		</tr>
		<tr>
			<td>Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Beam-Walk</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Beam</td>
			<td>home built</td>
			<td></td>
			<td>wood 38-1/2&#34; l x 1-3/4&#34; h x 1&#34; w sealed with polyurethane varnish (~ 37&#34; off floor)</td>
		</tr>
		<tr>
			<td>escape box</td>
			<td>home built</td>
			<td></td>
			<td>woodpainted black 12 1/2 &#34; l x 9&#34; h x 7-1/4&#34; w</td>
		</tr>
		<tr>
			<td>nails (pegs)</td>
			<td></td>
			<td></td>
			<td>2&#34;</td>
		</tr>
		<tr>
			<td>hinges</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>clamps</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>white noise machine</td>
			<td>San Diego Instruments 
			9155 Brown Deer Rd, Suite 8 San Diego, CA 92121 
			Phone: (858)530-2600</td>
			<td></td>
			<td>http://www.sandiegoinstruments.com/libraries/misc/datasheets/whitenoise.pdf</td>
		</tr>
		<tr>
			<td>light</td>
			<td>Home Depot</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>Morris Water Maze</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>fiberglass pool</td>
			<td>manufacturer unknown</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>(similar to one made by SDI)</td>
			<td>San Diego Instruments</td>
			<td>7000-0723</td>
			<td>72&#34; diameter x 30&#34; deep (~ 500 gal)</td>
		</tr>
		<tr>
			<td>plexiglass platform</td>
			<td>hand-made by Maggie Parsley</td>
			<td></td>
			<td>10 cm diameter, 26&#34; tall with silicone applied to the surface of the platform to provide a gripping surface</td>
		</tr>
		<tr>
			<td>(similar to one made by SDI)</td>
			<td>SDI</td>
			<td>7500-0272</td>
			<td></td>
		</tr>
		<tr>
			<td>plexiglass animal boxes w/ lids</td>
			<td>UTMB Machine Shop</td>
			<td></td>
			<td>2 boxes, 10&#34; w x 16&#34; L x 9&#34; h</td>
		</tr>
		<tr>
			<td>spot lights/ heat lamps</td>
			<td>Home Depot</td>
			<td></td>
			<td>3 around pool, 2 over boxes to dry animals</td>
		</tr>
		<tr>
			<td>AnyMaze</td>
			<td>San Diego Instruments 
			9155 Brown Deer Rd, Suite 8 San Diego, CA 92121 
			Phone: (858)530-2600</td>
			<td>/9001</td>
			<td>http://www.sandiegoinstruments.com/any-maze-video-tracking/</td>
		</tr>
	</tbody>
</table>

detecting behavioral deficits in rats after traumatic brain injury

随着创伤性颅脑损伤在平民和军人中的发病率不断上升, 脑外伤现在被认为是一种慢性疾病;然而, 很少有研究对损伤的长期影响的啮齿动物模型的创伤。这里所示的行为措施是在创伤后早期研究中建立的, 如两周, 直到两个月。这些方法中的一些以前被用于损伤后的后期, 长达一年, 但很少实验室。这里展示的方法是一个简短的神经学评估, 以测试反射, 平衡木平衡测试平衡, 光束步行到测试平衡和马达协调, 和工作记忆版本的莫里斯水迷宫, 可以敏感的赤字引用内存。在接受旁液体撞击伤 (外国证券) 或假损伤之前, 对雄性大鼠进行了神经、平衡和运动协调试验的处理和预训练。大鼠可以在短神经学评估 (neuroscore), 平衡木平衡, 和梁走多次, 而在水迷宫测试只能做一次。这种差异是因为老鼠能记住这项任务, 因此如果在同一动物身上反复试验, 就会混淆结果。在受伤后的一到三天的测试中, 在所有三非认知任务中检测到显著的差异。然而, 在以后的时间点 (3 月后), 光束行走任务的差异是不可探测的。在3月的平衡木平衡和6月的 neuroscore 中发现了赤字。在受伤后的12月内, 工作记忆中的赤字被检测出来, 而在12月的时间里, 一个参考记忆的缺陷就出现了。因此, 标准行为测试可以是有效的措施, 持续行为赤字后, 外国证券投资。

neuroscore 过程的结果 (图 2) 显示了假阳性 (在0天) 的潜在可能性, 以及此检测对细微差异的敏感性。当老鼠不习惯于程序的时候, 就会出现假阳性, 所以不完全放松。0天是在手术之前, 因此, 理想的情况下, 所有的老鼠都应该达到0之前进入一个研究的评分标准。1-3 天演示了此测试的灵敏度, 以检测分数的细微变化。虽然有一个分数高达21的潜力, 在这个模型中, 分数高于3是不寻常的。在本例中, 重复测量方差分析显示天真 (p = 0.78) 或假 (p = 0.09) 之间的天数之间没有差异;然而, 对于脑外伤组, 天 (p < 0.05) 之间存在差异。后期配对比较表明0天与1、2和3天有很大的不同。这一结果表明, 损伤在神经学评估中产生了微小而显著的变化。
进一步分析使用克鲁斯卡尔-瓦利斯测试比较天真, 假, 和脑外伤的每一天, 其次是 Tukey 的后 hoc测试, 以确定确切的差异所在。在0天, 测试统计为 13.37, p = 0.001, 假与天真有明显的不同 (p = 0.008)。理想情况下, 0 天的组之间不应该有任何区别, 因为没有治疗或程序被管理。在这种情况下, 老鼠应进一步习惯于程序, 或转移到一个非行为研究。在1天, 测试统计为 32.39, p = 9.75e-8, 带有后 hoc测试, 表明假和脑外伤与天真 (p = 0.002、 p = 5.9e-7 分别) 有明显的不同。在2天, 测试统计为 23.39, p = 8.34e-6, 假和脑外伤与幼稚不同 (p = 0.002, p = 6.8e-5)。在3天, 测试统计为 38.4, p = 4.59e-9, 再一次, 假和脑外伤与幼稚有显著差异 (p = 0.001, p = 2.1e-8, 分别)。这些结果表明, 假制剂也产生一些缺陷的神经评估在早期的创伤后的时间。
典型的平衡木平衡结果 (图 3) 在损伤后不久 (图 3, 左) 和在损伤后的时间点 (图 3, 右) 显示平衡木平衡测试对赤字的敏感性。束平衡试验对脑损伤的敏感性随着时间的推移而减小, 因为当未受伤的大鼠老化和增重时, 它们在光束上的平衡增加了难度。在以后的时间点, 光束被转动, 因此老鼠是平衡在更宽的一侧的光束。然而, 在受伤后的6月, 这个测试不再对伤害的影响, 因为年龄和/或重量混淆执行任务的能力 (图 3, 右)。另外, 治疗可能发生在前庭系统, 这些数据准确地反映了大鼠的平衡能力达到与对照组相同的水平。
在比较天真、虚伪和脑外伤的每一天, 我们使用克鲁斯卡尔-瓦利斯测试。损伤后早期时间点的结果显示在图 3中, 左侧。在0天, 克鲁斯卡尔-沃利斯测试发现测试统计值为 6.81, p = 0.033。这些组之间有很大的差异, Tukey 的后 hoc测试表明, 天真的组不同于假 (p = 0.038);然而, 所有的三组都意味着远远低于 2.0, 这表明所有的老鼠都达到了继续的标准。最好在0天的组之间没有区别, 但由于所有组都低于 2, 他们可以继续在研究。在 PID 1 上, 克鲁斯卡尔-瓦利斯测试统计为 69.72, p = 7.25e-16。Tukey 的后发测试表明, 脑损伤组与天真和虚假组有显著差异 (p = 4.9e-14, p = 9.1e-08, 分别)。在2天, 克鲁斯卡尔-瓦利斯测试统计为 62.84, p = 2.26e-14, 具有后 hoc测试, 显示不同于天真和虚假 (p = 1.0e-10, p = 2.1e-10 分别) 的创伤。在3天, 克鲁斯卡尔-瓦利斯测试统计为 62.69, p = 2.44e-14。后 hoc测试显示了不同于天真和虚假的创伤, (p = 9.6e-12, p = 1.7e-08, 分别)。此外, 我们还查看了每个组中的天数是否有差异。使用重复的度量方差分析, 对于天真, 天之间没有区别 (p = 0.367)。对于假和脑外伤有不同的天数之间的差异 (p = 0.002, p = 3.90e-29, 分别)。为假1显示的后 hoc配对比较与2天和3天 (p = 0.001) 显著不同p = 0.01, 分别), 而对于脑外伤, 天0是显着不同的形式天 1, 2 和 3 (p < 2 e-16,p = 5.5e-16, 分别为p = 2.7e-13。1天也明显不同于3天 (p = 0.036)。
在受伤6月后, 每天使用克鲁斯卡尔-沃利斯测试 (图 3, 右) 对天真、虚假和脑外伤进行比较。在0天, 测试统计的值为 3.36, p = 0.187, 因此在0天没有差异。所有的方法都低于 2, 这表明所有的老鼠和团体都符合在研究中继续的标准。在 PID 1 上, 测试统计为 6.11, p = 0.047;但是, 使用 Tukey 的后 hoc测试的后 hoc分析表明, 在对多个假设测试进行核算时, 这些组都没有显著差异。在2天, 测试统计为 4.09, p = 0.13, ns, 在3天, 测试统计为 2.91, p = 0.23, ns。因此, 在任何一天的伤害组之间没有区别。
此外, 观察治疗组内天数之间的差异, 反复测量方差分析显示, 天真、虚假和脑外伤的天数有显著差异 (p = 0.0003, p = 2.61e-5, p = 5.59e-7, 分别为:图 3, 右)。后 hoc测试演示了以下差异。对于天真来说, 0 天与1、2和3天有很大不同 (分别为p = 0.002、 p = 0.044、 p = 0.004。对于假, 所有的日子都有明显的不同: 天0是显着不同的天 1, 2, 和 3 (p = 0.0006, p = 0.001, p = 0.0006, 分别);1天与天2和3有明显不同 (分别为p = 0.031、 p = 0.0006);2天与3天显著不同 (p = 0.044)。对于脑外伤, 0 天是显着不同的天 1, 2 和 3 (p = 0.0005, p = 0.0008, p = 0.0005, 分别)。
光束遍历测试的结果显示在两个时间点 (图 4)。与平衡木的平衡类似, 这项测试在受伤后及早检测出赤字 (图 4, 左侧)。然而, 在受伤6月后, 各组之间没有显著差异 (图 4, 右), 建议在受伤组中发生愈合。这一结果可能反映了更先进的年龄和增加的体重的影响。
为了比较单纯的、假的和外伤后每天的脑外伤, 采用了单因子方差分析方法。在0天 (F = 0.859, p = 0.426) 上没有差异, 所有延迟都低于5秒, 这表明所有的老鼠都符合在研究中继续的标准。在 PID 1, 有一个重要的测试统计为 15.36, p = 1.18e-6。Tukey 的post测试表明了脑外伤和单纯性 (p = 0.000004) 和脑外伤和假 (p = 0.0001) 之间的显著差异。在2天, 组之间存在显著差异 (F = 9.49, p = 0.0002)。后 hoc测试揭示了脑外伤和单纯性 (p = 0.0002) 和脑外伤和假 (p = 0.005) 之间的差异。在3天, 总体测试统计值等于 6.27, p = 0.0025, 表示组之间存在差异。Tukey 的后 hoc测试显示, 脑外伤与单纯的和假的不同 (p = 0.003, p = 0.035, 分别)。
采用单向重复测量方差分析, 探讨治疗组内天数的差异。首先检查每个组的度的假设。内部因素 (天) 不符合度假定为天真或假小组, 因而连续更正, 温室-格里尔被申请了对那些小组。对于假, 在天之间没有区别 (p = 0.066), 为天真和脑外伤有 (p = 0.006, p = 2.89E-7, 分别)。后 hoc比较显示为天真, 差异介于0天和1天之间 (p = 0.003)。为创伤性脑损伤, 区别是在天0和天之间 1, 2 和 3 (p = 9.2e-6, p = 0.0005, p = 0.002, 分别), 并且有区别在天1和天3之间 (p = 0.018)。
在受伤后6月, 在任何一天 (天 0, F = 0.315, p = 0.732;1天, F = 0.336, p = 0.717;2天, F = 0.5, p = 0.61;3天, F = 1.17, p = 0.322;图 4, 右)。当比较每个组内天数之间的差异时, 在脑外伤组 (p = 0.026) 中有显著差异, 日0与1、2和3天不同 (p = 0.026, p = 0.002, p = 0.002)。对于天真或虚假的任何天数 (p = 0.104、 p = 0.063 分别) 没有任何区别。
来自莫里斯水迷宫工作记忆版本的数据可以用不同的方式绘制出来。在这里, 我们演示了3月的结果 (图 5, 左) 和12月 (图 5, 右) 受伤后使用两个折线图来表示时间过程, 并通过方框图来提供数据的总体汇总 (数字 5, 底部)。然后, 我们可以可视化试验1比较和试验2比较独立于每一天, 以及整体的差异, 由于伤害。试验1潜伏期表示参考记忆和试验2潜伏期描述工作记忆。
损伤后3月鼠的数据显示在图 5中, 左侧。对于试用 1 (图 5, 左上角), 当比较天真, 假, 和脑外伤, 只有4天显示的组之间的显著差异 (F = 4.12, p = 0.025), 与后 hoc Tukey 的测试表明, 脑外伤是不同于天真 (p = 0.019)。对于试用版 2 (图 5, 中左), 在1天 (F = 5.93, p = 0.006) 上有显著的差异, 并带有后 hoc分析, 表明与假 (p = 0.005) 不同。在3月 (p = 0.56) 中, 重复测量方差分析未发现损伤组之间的总体差异。这些结果表明, 这些大鼠有小而严重的赤字, 以及工作记忆在3月后的损伤。
在受伤后12月, 比较试验1天真, 假, 和颅脑外伤 (图 5, 右), 重复测量方差分析显示了一个重大的整体影响的伤害 (F = 3.94, p = 0.03)。配对比较显示, 颅脑损伤与单纯性和假 (p = 0.043 和p = 0.006) 有显著差异 (图 5, 右下角)。此外, 通过比较每一天的伤害组, 使用单向方差分析, 在3天 (F = 7.28, p = 0.003) 中检测到显著的差异。后 hoc比较显示, 脑外伤与假 (p = 0.0018) (图 5右上角) 不同。在试验2中, 重复测量方差分析发现, 由于伤害 (F = 3.97, p = 0.029) 的差异很大, 与后 hoc配对比较检测脑外伤和假 (p = 0.017) 之间的差异 (图5, 右下角)。每天的单程方差分析在2和4天发现了显著的差异。在2天 (F = 4.02, p = 0.028), Tukey 的后 hoc测试发现, 脑外伤与假 (p = 0.023) 不同。在4天 (F = 4.12, p = 0.026) 上,后 hoc分析发现了脑外伤和假 (p = 0.025) 之间的区别 (图 5, 中间右)。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56044/56044fig1.jpg"> 图1。水迷宫图.这张图展示了可能的平台位置 (1, 2, 3, 4) 和起始点 (N, S, E, W) 为工作记忆莫里斯水迷宫。老鼠可以从每个起始位置/平台配对中进行两次试验。有一个十五年代间试验间隔和4分钟休息在温暖的房间在两对试验共计四对每每日会议的试验。<a href="//cloudflare.jove.com/files/ftp_upload/56044/56044fig1large.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/56044/56044fig2.jpg"> 图2。neuroscore 测试的结果.所有的老鼠在0天前接受了简单的反射测试任务 (有关训练、测试和评分的详细信息, 请参阅文本)。结果显示为中值 (黑线)、第一个和第三四 (框的边界) 和 10th和 90th分 (误差线)。这个平均值也被红线和外围点显示为黑点。数据被提出为天0基线和损伤后天1-3。对每个时间点的后 hoc t测试的结果显示在图表上: * p < 0.001 与颅脑损伤日 0;^ p < 0.001 与同一天的天真。<a href="//cloudflare.jove.com/files/ftp_upload/56044/56044fig2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56044/56044fig3.jpg"> 图3。梁平衡试验结果.所有的老鼠都经过训练, 在平衡木上保持平衡, 直到他们在六十年代连续三次试验中取得平衡 (关于训练、测试和评分的细节参见文本)。在随后的测试中, 大鼠的得分是从 1-6, 1 表示正常平衡, 6 表示没有试图停留在光束上。结果显示为中值 (黑线)、第一个和第三四 (框的边界) 和 10th和 90th分 (误差线)。这个平均值也被红线和外围点显示为黑点。数据显示0天基线评分, 受伤后天数 1-3 (左), 和6月后受伤 (右)。每个时间点的后 hoc t测试的结果都显示在关系图上。0-3 天: * p < 0.001 vs 天脑外伤 0; ^ p < 0.001 vs 同一天天真;@ p < 0.001 vs 同一天假。6月: * p < 0.001vs 天脑外伤 0; # p < 0.001 vs 天真日 0;& p < 0.001 与假日0。<a href="//cloudflare.jove.com/files/ftp_upload/56044/56044fig3large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/56044/56044fig4.jpg"> 图4。梁式行走试验结果.所有的老鼠都经过训练, 在柱子之间的横梁上穿行, 以避免进入一个安全箱。他们接受了训练, 直到他们在三连续的试验遇见了≤ 5 s 标准 (参见文本关于训练、测试和计分的细节)。基线测试在0天完成, 老鼠随后在受伤后1-3 天进行测试 (左)。在受伤后的6月内, 还有一组老鼠被重新测试 (右)。结果被绘成中值 (黑线)、第一个和第三四 (框的边界) 和 10th和 90th分 (误差线)。这个平均值也被红线和外围点表示为黑点。每个时间点的后 hoc测试的结果显示在关系图上。0-3 天: * p < 0.001 vs 天脑外伤 0; ^ p < 0.001 vs 同一天天真;@ p < 0.001 vs 同一天假;6月: * p < 0.001vs 天脑外伤 0.<a href="//cloudflare.jove.com/files/ftp_upload/56044/56044fig4large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/56044/56044fig5.jpg"> 图5。工作记忆的结果莫里斯水迷宫.结果显示在3月 (左栏) 和12月 (右栏) 的大鼠单独组。上部面板显示了在五测试日的两个试验配对的第一次试验中, 平均潜伏期 (在老鼠找到隐藏平台时所用的时间)。中间面板显示每一天的第二次试验的平均潜伏期。后 hoc分析的结果显示在图表上 (* p < 0.05 与同一天假; ^ p < 0.05 vs 同一天天真)。下部面板总结显示中位数 (黑线)、25th和 75th分 (框边界) 和 10th和 90th分 (误差线) 的结果。这个平均值也被红线和外围点显示为黑点。后 hoc分析的结果显示在关系图上 (*p < 0.05 与同一个试验假, ^ p < 0.05 vs 相同的试验天真)。<a href="//cloudflare.jove.com/files/ftp_upload/56044/56044fig5large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>

Watch this Scientific Journal Video about Detecting Behavioral Deficits in Rats After Traumatic Brain Injury at JoVE.com

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

在这里提出的行为测试的目的是检测脑外伤后大鼠的功能性缺损。四具体的测试表明, 检测行为的缺陷, 以反映对特定脑区的损害, 有时延长到一年后受伤。

颅脑损伤后大鼠行为缺陷的检测

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

detecting-behavioral-deficits-in-rats-after-traumatic-brain-injury

Universidad de Cartagena UDEC

Research

JoVE Journal

Behavior

17.8K 次观看.  University of Texas Medical Branch. 在这里提出的行为测试的目的是检测脑外伤后大鼠的功能性缺损。四具体的测试表明, 检测行为的缺陷, 以反映对特定脑区的损害, 有时延长到一年后受伤。

视频: Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological impairments 1. Two pervasive and disabling symptoms experienced by TBI survivors, memory deficits and a reduction in seizure threshold, are thought to be mediated by TBI-induced hippocampal dysfunction 2,3. In order to demonstrate how altered hippocampal circuit function adversely affects behavior after TBI in mice, we employ lateral fluid percussion injury, a commonly used animal model of TBI that recreates many features of human TBI including neuronal cell loss, gliosis, and ionic perturbation 4-6.
	Here we demonstrate a combinatorial method for investigating TBI-induced hippocampal dysfunction. Our approach incorporates multiple ex vivo physiological techniques together with animal behavior and biochemical analysis, in order to analyze post-TBI changes in the hippocampus. We begin with the experimental injury paradigm along with behavioral analysis to assess cognitive disability following TBI. Next, we feature three distinct ex vivo recording techniques: extracellular field potential recording, visualized whole-cell patch-clamping, and voltage sensitive dye recording. Finally, we demonstrate a method for regionally dissecting subregions of the hippocampus that can be useful for detailed analysis of neurochemical and metabolic alterations post-TBI.
	These methods have been used to examine the alterations in hippocampal circuitry following TBI and to probe the opposing changes in network circuit function that occur in the dentate gyrus and CA1 subregions of the hippocampus (see Figure 1). The ability to analyze the post-TBI changes in each subregion is essential to understanding the underlying mechanisms contributing to TBI-induced behavioral and cognitive deficits. 
	The multi-faceted system outlined here allows investigators to push past characterization of phenomenology induced by a disease state (in this case TBI) and determine the mechanisms responsible for the observed pathology associated with TBI.

A multi-faceted approach to investigating functional changes to hippocampal circuitry is explained. Electrophysiological techniques are described along with the injury protocol, behavioral testing and regional dissection method. The combination of these techniques can be applied in similar fashion for other brain regions and scientific questions.

调查轻度创伤性脑损伤海马电路功能的改变

Traumatic Brain Injury (TBI) afflicts more than 1.7 million people in the United States each year and even mild TBI can lead to persistent neurological ...

科研

神经科学

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

The modified weight-drop technique is an easy, cost-effective procedure used for the induction of mild traumatic brain injury in juvenile rats. This novel technique produces clinically relevant symptomology that will advance the study of mild traumatic brain injury (mTBI) and concussion.

轻度脑外伤的幼年大鼠一种新模式

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor ...

医学

Assessing Dominant-Submissive Behavior in Adult Rats Following Traumatic Brain Injury

Competition over resources such as food, territory, and mates significantly influences relationships within animal species and is mediated through social hierarchies that are often based on dominant-submissive relationships. The dominant-submissive relationship is a normal behavioral pattern among the individuals of a species. Traumatic brain injury is a frequent cause of social interaction impairment and the reorganization of dominant-submissive relationships in animal pairs. This protocol describes submissive behavior in adult male Sprague-Dawley rats after the induction of traumatic brain injury using a fluid-percussion model compared to naive rats through a series of dominant-submissive tests performed between 29 days and 33 days after induction. The dominant-submissive behavior test shows how brain injury can induce submissive behavior in animals competing for food. After traumatic brain injury, the rodents were more submissive, as indicated by them spending less time at the feeder and being less likely to arrive first at the trough compared to the control animals. According to this protocol, submissive behavior develops after traumatic brain injury in adult male rats.

The present protocol describes a rat model of fluid percussion-induced traumatic brain injury followed by a series of behavioral tests to understand the development of dominant and submissive behavior. Using this model of traumatic brain injury in conjunction with specific behavioral tests enables the study of social impairments following brain injury.

评估创伤性脑损伤后成年大鼠的显性顺从行为

Competition over resources such as food, territory, and mates significantly influences relationships within animal species and is mediated through social ...

行为学

Gathering Self-Initiated Rat Behavioral Data to Characterize Post-Stroke Deficits

Behavioral testing in rat models is frequently utilized for diverse purposes, including psychological, biomedical, and behavioral research. Many traditional approaches involve individual, one-on-one testing sessions between a single researcher and each animal in an experiment. This setup can be very time consuming for the researcher, and their presence may impact the behavioral data in unwanted ways. Additionally, traditional caging for rat research imposes a lack of enrichment, exercise, and socialization that would normally be typical for the species, and this context may also skew the results of behavioral data. Overcoming these limitations may be worthwhile for several research applications, including the study of acquired brain injury. Here, an example method is presented for automatically training and testing individual rat behavior in a colony cage without the presence of humans. Radio frequency identification can be utilized to tailor sessions to the individual rat. The validation of this system occurred in the example context of measuring skilled forelimb motor performance before and after stroke. Traditional characteristics of post-stroke behavioral impairments and novel measures enabled by the system are measured, including success rate, various aspects of pull force, bout analysis, initiation rate and patterns, session duration, and circadian patterns. These variables can be collected automatically with few limitations; though the apparatus removes experimental control of exposure, timing and practice, the validation produced reasonable consistency in these variables from animal to animal.

A system for acquiring data from self-initiated individual behavior sessions within a social colony cage setting is presented. The efficacy of this system is demonstrated using an automated skilled reach assessment, enabling the characterization of post-stroke motor impairments, potential behavioral alterations related to motivation, circadian variations, and other innovative dependent variables.

收集自发的大鼠行为数据以表征中风后缺陷

Behavioral testing in rat models is frequently utilized for diverse purposes, including psychological, biomedical, and behavioral research. Many ...

Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes demonstrate the ability to record action potentials from individual or small groups of neurons. Such recorded signals have successfully been used to allow patients to interface with or control&#160;computers, robotic limbs, and their own limbs. However, previous animal studies have shown that a microelectrode implantation in the brain not only damages the surrounding tissue but can also result in functional deficits. Here, we discuss a series of behavioral tests to quantify potential motor impairments following the implantation of intracortical microelectrodes into the motor cortex of a rat. The methods for open field grid, ladder crossing, and grip strength testing provide valuable information regarding the potential complications resulting from a microelectrode implantation. The results of the behavioral testing are correlated with endpoint histology, providing additional information on the pathological outcomes and impacts of this procedure on the adjacent tissue.

We have shown that a microelectrode implantation in the motor cortex of rats causes immediate and lasting motor deficits. The methods proposed herein outline a microelectrode implantation surgery and three rodent behavioral tasks to elucidate potential changes in the fine or gross motor function due to implantation-caused damage to the motor cortex.

大鼠运动皮质微电极植入所致功能缺损的啮齿动物行为检测

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes ...

生物工程

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

The overall goal of this procedure is to obtain quantitative microstructural information of the hippocampus in a rat with mild traumatic brain injury. This is done using an advanced diffusion-weighted magnetic resonance imaging protocol and region-of-interest based analysis of parametric diffusion maps.

轻度创伤性脑损伤大鼠海马学的高级扩散成像

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous ...

A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats

The purpose of this study was to establish and validate an animal brain ischemia model in the recovery and sequela stages. A middle cerebral artery occlusion/reperfusion (MCAO/R) model in male Sprague-Dawley rats was chosen. By changing the rat&#39;s weight (260&#8722;330 g), the thread bolt type (2636/2838/3040/3043) and the brain infarct time (2-3 h), a higher Longa&#39;s score, a larger infarct volume and a greater model success ratio were screened using the Longa&#39;s score and TTC staining. The optimum model condition (300 g, 3040 thread bolt, 3 h brain infarct time) was acquired and used in a 1-90 day observation period after reperfusion via assessment of sensorimotor functions and infarct volume. At these conditions, the bilateral asymmetry test had a significant difference from 1 to 90 days, and the grid-walking test had a significant difference from 1 to 60 days; both differences could be a suitable sensorimotor functional test. Thus, the most appropriate condition of a novel rat model in the recovery and sequela stages of brain ischemia was found: 300 g rats that underwent MCAO with a 3040 thread bolt for a 3 h brain infarct and then reperfused. The appropriate sensorimotor functional tests were a bilateral asymmetry test and a grid-walking test.

The&#160;purpose of this study is to establish and validate an animal model for research in the recovery and sequela stages of brain ischemia by testing brain infarction and sensorimotor function after middle cerebral artery occlusion/reperfusion (MCAO/R) after 1-90 days in rats.

评估大鼠急性中风后脑恢复的临床前模型

The purpose of this study was to establish and validate an animal brain ischemia model in the recovery and sequela stages. A middle cerebral artery ...

A Metric Test for Assessing Spatial Working Memory in Adult Rats Following Traumatic Brain Injury

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of human studies, animal models provide suitable alternatives to test treatment methods, and to study the mechanisms and related complications of the condition. Experimental rodent models have historically been the most widely used due to their accessibility, low cost, reproducibility, and validated approaches. A metric test, which tests the ability to recall the placement of two objects at various distances and angles from one another, is a technique to study impairment in spatial working memory (SWM) after TBI. The significant advantages of metric tasks include the possibility of dynamic observation, low cost, reproducibility, relative ease of implementation, and low stress environment. Here, we present a metric test protocol to measure impairment of SWM in adult rats after TBI. This test provides a feasible way to evaluate physiology and pathophysiology of brain function more effectively.

Traumatic brain injury (TBI) is commonly associated with memory impairment. Here, we present a protocol to assess spatial working memory after TBI via a metric task. A metric test is a useful tool to study spatial working memory impairment after TBI.

创伤性脑损伤后评估成年大鼠空间工作记忆的指标测试

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of ...

Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of closed-head mTBI in the preclinical setting to increase translatability to the clinical population. The awake closed-headed injury (ACHI) model uses a modified controlled cortical impactor to deliver closed-headed injury, inducing clinically relevant behavioral deficits without the need for a craniotomy or the use of an anesthetic.
This technique does not normally induce fatalities, skull fractures, or brain bleeds, and is more consistent with being a mild injury. Indeed, the mild nature of the ACHI procedure makes it ideal for studies investigating repetitive mTBI (r-mTBI). Growing evidence indicates that r-mTBI can result in a cumulative injury that produces behavioral symptoms, neuropathological changes, and neurodegeneration. r-mTBI is common in youths playing sports, and these injuries occur during a period of robust synaptic reorganization and myelination, making the younger population particularly vulnerable to the long-term influences of r-mTBI.
Further, r-mTBI occurs in cases of intimate partner violence, a condition for which there are few objective screening measures. In these experiments, synaptic function was assessed in the hippocampus in juvenile rats that had experienced r-mTBI using the ACHI model. Following the injuries, a tissue slicer was utilized to make hippocampal slices to evaluate bidirectional synaptic plasticity in the hippocampus at either 1 or 7 days following the r-mTBI. Overall, the ACHI model provides researchers with an ecologically valid model to study changes in synaptic plasticity following mTBI and r-mTBI.

Here, it is demonstrated how an awake closed-head injury model can be used for examining the effects of repeated mild traumatic brain injury (r-mTBI) on synaptic plasticity in the hippocampus. The model replicates important features of r-mTBI in patients and is used in conjunction with in vitro electrophysiology.

使用轻度创伤性脑损伤的清醒闭合性头部损伤模型评估突触可塑性的变化

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of ...

在 mTBI 大鼠模型中验证损伤反应和行为评估

Rat Model of Closed-Head Mild Traumatic Injury and its Validation

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful insights, developing a stable and reproducible animal model is essential. In this study, we report a detailed description of a closed-head mTBI model and a representative validation method using Sprague-Dawley rats to verify the modeling effect. The model involves dropping a 550 g mass weight from a height of 100 cm directly onto the head of a rat on a destructible surface, followed by a 180-degree turn. To assess the injury, rats underwent a series of neurobehavioral assessments 10 min post-injury, including time of loss of consciousness, first seeking-behavior time, escape ability, and beam balance ability test. During the acute and subacute stages following the injury, behavioral tests were conducted to assess motor coordination ability (Beam task), anxiety (Open Field test), and learning and memory abilities (Morris Water Maze test). The closed-head mTBI model produced a consistent injury response with minimal mortality and replicated real-life situations. The validation method effectively verified the model development and ensured the stability and consistency of the model.

作者聚焦:推进创伤性脑损伤研究 - 用于准确复制和快速评估的闭头模型 

Here, we present a closed-head mild traumatic brain injury (mTBI) rat model and its validation exhibiting remarkable similarity to human mTBI concerning behavioral manifestations during the acute and subacute stages.

闭合头轻度创伤大鼠模型及其验证

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful ...