Name: a battery of motor tests in a neonatal mouse model of cerebral palsy
Uploaded: 2016-11-03T12:30:00.000+00:00
Duration: 10 min 2 s
Description: Watch this Scientific Journal Video about A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy at JoVE.com

We would like to thank everyone at Shriners Hospital Pediatric Research Center, in particular Dr. Mickey Seltzer, of whom without his support, this work would not have been funded. In addition, we would like to thank Isha Srivastava, who contributed to early data collection and Amy He, who helped with the figures. This study was funded by Shriners Hospitals for Children. No funding source played a role in experimental design or decision to submit the paper for publication.

<ol>
	<li>Nakamura, M., Bregman, B. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differences+in+neurotrophic+factor+gene+expression+profiles+between+neonate+and+adult+rat+spinal+cord+after+injury.">Differences in neurotrophic factor gene expression profiles between neonate and adult rat spinal cord after injury.</a> Exp Neurol. 169 (2), 407-415 (2001).</li><li>Widenfalk, J., Lundstr&#246;mer, K., Jubran, M., Brene, S., Olson, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurotrophic+factors+and+receptors+in+the+immature+and+adult+spinal+cord+after+mechanical+injury+or+kainic+acid.">Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid.</a> J Neurosci. 21 (10), 3457-3475 (2001).</li><li>Fern&#225;ndez-L&#242;pez, D., Faustino, J., 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=Blood-brain+barrier+permeability+is+increased+after+acute+adult+stroke+but+not+neonatal+stroke+in+the+rat.">Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat.</a> J Neurosci. 32 (28), 9588-9600 (2012).</li><li>Cusick, C. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extensive+cortical+reorganization+following+sciatic+nerve+injury+in+adult+rats+versus+restricted+reorganization+after+neonatal+injury:+implications+for+spatial+and+temporal+limits+on+somatosensory+plasticity.">Extensive cortical reorganization following sciatic nerve injury in adult rats versus restricted reorganization after neonatal injury: implications for spatial and temporal limits on somatosensory plasticity.</a> Prog Brain Res. 108, 379-390 (1996).</li><li>Barrett, C. P., Donati, E. J., Guth, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differences+between+adult+and+neonatal+rats+in+their+astroglial+response+to+spinal+injury.">Differences between adult and neonatal rats in their astroglial response to spinal injury.</a> Exp Neurol. 84 (2), 374-385 (1984).</li><li>Villapol, S., Gelot, A., Renolleau, S., Charriaut-Marlangue, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Astrocyte+Responses+after+Neonatal+Ischemia:+The+Yin+and+the+Yang.">Astrocyte Responses after Neonatal Ischemia: The Yin and the Yang.</a> Neuroscientist. 14 (4), 339-344 (2008).</li><li>Craig, A., Ling Luo, N., 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=Quantitative+analysis+of+perinatal+rodent+oligodendrocyte+lineage+progression+and+its+correlation+with+human.">Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human.</a> Exp Neurol. 181 (2), 231-240 (2003).</li><li>Shen, Y., Liu, X. B., Pleasure, D. E., Deng, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Axon-glia+synapses+are+highly+vulnerable+to+white+matter+injury+in+the+developing+brain.">Axon-glia synapses are highly vulnerable to white matter injury in the developing brain.</a> J Neurosci Res. 90 (1), 105-121 (2012).</li><li>Shen, Y., Plane, J. M., Deng, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+models+of+periventricular+leukomalacia.">Mouse models of periventricular leukomalacia.</a> J Vis Exp. (39), (2010).</li><li>Fox, W. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reflex-ontogeny+and+behavioural+development+of+the+mouse.">Reflex-ontogeny and behavioural development of the mouse.</a> Anim Behav. 13 (2), 234-241 (1965).</li><li>Tremml, P., Lipp, H. P., M&#252;ller, U., Ricceri, L., Wolfer, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurobehavioral+development,+adult+openfield+exploration+and+swimming+navigation+learning+in+mice+with+a+modified+beta-amyloid+precursor+protein+gene.">Neurobehavioral development, adult openfield exploration and swimming navigation learning in mice with a modified beta-amyloid precursor protein gene.</a> Behav Brain Res. 95 (1), 65-76 (1998).</li><li>Wahlsten, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+developmental+time+scale+for+postnatal+changes+in+brain+and+behavior+of+B6D2F2+mice.">A developmental time scale for postnatal changes in brain and behavior of B6D2F2 mice.</a> Brain Res. 72 (2), 251-264 (1974).</li><li>Balasubramaniam, J., Xue, M., Del Bigio, . <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+motor+deficit+following+periventricular+hemorrhage+in+neonatal+rats:+A+potential+model+for+human+cerebral+palsy.">Long-term motor deficit following periventricular hemorrhage in neonatal rats: A potential model for human cerebral palsy.</a> J Cerebr Blood F Met. , (2005).</li><li>Williams, E., Scott, 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=The+Development+of+Social+Behavior+Patterns+in+the+Mouse,+in+Relation+to+Natural+Periods.">The Development of Social Behavior Patterns in the Mouse, in Relation to Natural Periods.</a> Behaviour. 6 (1), 35-65 (1954).</li><li>Heyser, C. J., Crawley, J. Q., 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=Assessment+of+developmental+milestones+in+rodents.">Assessment of developmental milestones in rodents.</a> Current protocols in neuroscience. Chapter 8, (2004).</li><li>Corti, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Grip strength TREAT-NMD: Experimental protocols for SMA animal models. , (2014).</li><li>Corti, S., Nizzardo, M., 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=Neural+stem+cell+transplantation+can+ameliorate+the+phenotype+of+a+mouse+model+of+spinal+muscular+atrophy.">Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy.</a> J Clin Invest. 118 (10), 3316-3330 (2008).</li><li>Grondard, C., Biondi, O., 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=Regular+exercise+prolongs+survival+in+a+type+2+spinal+muscular+atrophy+model+mouse.">Regular exercise prolongs survival in a type 2 spinal muscular atrophy model mouse.</a> J Neurosci. 25 (33), 7615-7622 (2005).</li><li>El-Khodor, B. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+Phenotyping+for+Neonates.">Behavioral Phenotyping for Neonates.</a> Experimental Protocols for SMA animal models. , (2011).</li><li>El-Khodor, B. F., Edgar, N., 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=Identification+of+a+battery+of+tests+for+drug+candidate+evaluation+in+the+SMNDelta7+neonate+model+of+spinal+muscular+atrophy.">Identification of a battery of tests for drug candidate evaluation in the SMNDelta7 neonate model of spinal muscular atrophy.</a> Exp Neurol. 212 (1), 29-43 (2008).</li><li>Venerosi, A., Ricceri, L., Scattoni, M. L., Calamandrei, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prenatal+chlorpyrifos+exposure+alters+motor+behavior+and+ultrasonic+vocalization+in+CD-1+mouse+pups.">Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in CD-1 mouse pups.</a> Environ Health. 8 (12), (2009).</li><li>Hill, J. M., Lim, M. A., Stone, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Developmental+milestones+in+the+newborn+mouse.">Developmental milestones in the newborn mouse.</a> Neuromethods 39: Neuropeptide Techniques. , (2008).</li><li>Yu, Y., Keshner, A. E., Tucker, C. A., Thompson, E. D., Lauer, R. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual+dependence+influences+postural+responses+to+continuous+visual+perturbation+in+adults+with+spastic+cerebral+palsy.">Visual dependence influences postural responses to continuous visual perturbation in adults with spastic cerebral palsy.</a> , (2016).</li><li>Carlson, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+four+limb+hanging+tests+to+monitor+muscle+strength+and+condition+over+time.">The use of four limb hanging tests to monitor muscle strength and condition over time.</a> Experimental Protocols for SMA animal models. , (2011).</li><li>Gordon, A. M., Duff, S. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relation+between+clinical+measures+and+fine+manipulative+control+in+children+with+hemiplegic+cerebral+palsy.">Relation between clinical measures and fine manipulative control in children with hemiplegic cerebral palsy.</a> Dev Med Child Neurol. 41 (9), 586-591 (1999).</li><li>Futagi, Y., Toribe, Y., Suzuki, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+grasp+reflex+and+moro+reflex+in+infants:+hierarchy+of+primitive+reflex+responses.">The grasp reflex and moro reflex in infants: hierarchy of primitive reflex responses.</a> Int J Pediat. , (2012).</li></ol>

The authors declare that they have no competing financial interests.

인간과 설치류 사이에 수행 된 행동 검사는 인간의 증상에 직접 관련이 그 세포 및 분자 응답 사이에 중복이있는 경우 인간의 질병을 연구하는 동물 모델을 사용하면에만 관련이 있습니다. 소아 질환 연구와 주요 이슈 중 하나는 많은 연구자는 질병 과정에 중요 할 수있다 발달 차이를 고려하지 않고, 상기 모델뿐만 아니라 성체 설치류 행동 평가를 만들 성인 쥐를 사용한다. 7 (7 일 설치류 - - 32주 후 산후 2 일에 해당 (28)의 예를 들면, 인간 CNS 개발) 이러한 문제 때문에, 소아 질환의 사용에 대한 연구뿐만 아니라 적절한 조정 발달 시간 포인트가 중요하다 뿐만 아니라 행동 테스트는 적절한 모터, 감각 또는 재귀 발달 행동을 검토 것이다. 각각의 새로운 신생아 질병 모델 개발로 따라서, 엄격하게 휴대 것을 보장하기 위해 테스트해야및 행동 반응은 설치류와 인간 사이의 가장 적절한 번역 데이터를 제공 할 것입니다. 뇌성 마비는 성인으로 지속 모터 질환이다. 오늘날 사용 가능한 뇌성 많은 모델의 한가지 문제점은 소아 환자에서 볼 수 결손과 상관 반복 표준화 모터 테스트의 부족이다. 신생아 마우스에서 저산소증, 허혈 및 염증을 결합한 새로운 모델에서, 모터의 동작은 신생 생쥐의 특정 테스트의 전지를 사용하여 평가 하였다. 정량적보고 주관성을 감소 및 증가시키기 위해 여러 테스트를 표준화 할 수 측정을 평가하는 매우 구체적인 쉬우나 포함하도록 변형되었다. 또한, 전면 및 뒷다리 평가는 별도로 수행 될 수 있고, 왼쪽 / 오른쪽 차이가 결정될 수있다. 시험이 배터리는 나이 2 주까지 신생아 쥐에 대한 구체적인이다. 이 CP 모델을 보여줍니다발달 반사에 (보행, 뒷다리 발 각도) 걷기의 어려움뿐만 아니라 사지 고유의 약점 (사 사지 서스펜션, 뒷다리 서스펜션) 및 적자 (반사를 잡고). 본 연구에서 하나의 평가시기가 검토되었지만, 이러한 결핍은 시간을 추적 할 수있다. 이러한 테스트의 폭스의 배터리 또는 발달 이정표 (15)의 Heyser의 평가와 신생아에서 사용할 수있는 테스트의 다른 배터리가있다. 그러나 이러한 테스트는 그 응답 신생아는 아직 개발되어 있기 때문에 동일하지 않을 수 있습니다 성인에 신생아를 비교합니다. 폭스의 배터리와 Heyser의 Assement 테스트는 오히려 (강도에 따라 각도, 자세 등) 객관적인 데이터보다, 이분법 (예 또는 아니오) 평가와 관찰 주관적인 정보에 의존합니다. 때문에 이러한 테스트의 subjectiveness, 많은 과학자들은 따라서 다른 사람과 한계 비교할 수없는 결과를 만드는 기준을 적용, 추가 또는 삭제했다특정 질병 또는 장애에 대한 기준을 확립 부족의 관점에서 데이터의 유용성을 보내고. 질적 구체적 신생아를 시험하기위한 표준화 된 모터 시험 한 세트를 구축함으로써, 개별 그룹 연구 결과를 정확하고 확실하게보고되고 비교 될 수있다.

소아 부상이나 설치류를 사용하여 질병의 새로운 모델을 개발하는 것은 인해 급속하게 신경 부상에서 회복 모두 쥐와 생쥐의 놀라운 능력을 종종 어렵다. 따라서, 새로운 소아 질병 모델, 철저하게 행동 결과와 함께 손에 손을 이동해야하는 세포 및 분자 변경 검사의 유효성을 검사하기 위해있다. 여러 가지면에서 기능적인 행동 복구는 치료 또는 번역 관련성의 관점에서 기본 세포 변화보다 더 중요 할 수있다. 연구자는 성인 및 신생아 손상에 대한 자세한 내용으로서, 자신의 응답은 매우 상이하고, 둘 사이에 추정 할 수없는 것이 명백하다. 예를 들어, 마우스는 신생아 신경 성장 인자, 뇌 유래 신경영 양인자, 뉴로 트로 핀 -3 및 척수 손상 1,2- 다음 아교 세포주 유래 신경 영양성 인자의 상이한 레벨을 표시. 또한 신생아 뇌졸중 3 D 후 상당한 혈뇌 장벽 누설이말초 신경 손상 사 후 대뇌 피질의 신경 세포의 재 배열을 emonstrate 및 척수 손상 및 저산소증 - 허혈 5,6 다음의 지연 또는 둔화 astrogliosis 있습니다. 따라서 번역 소아 연구가 발달 해당하는 모델을 사용하는 것이 그 모델은 셀룰러 / 분자 변화와 연령에 적합한 행동 검사에 대해 평가하는 것이 중요하다. 1000 출산 매년 (NIH) : 뇌성 마비 (CP)는 3에 영향을 미치는 모터 질환이다. CP 어린이는 질병의 심각도에 따라 증상과 병적 조건의 범위를 나타낸다. 이동 및 조정 어려움 모터 발달 이정표 도달 지연과 함께 가장 흔한 증상이다. 다른 증상은 비정상적인 근육 톤을 (증가 또는 감소 중), 미세 운동 능력, 어려움 산책, 과도한 기뻐 날뛰는과 삼키는 및 음성 지연 (NIH)을 감소 있습니다. CP의 근본 원인으로 여겨진다또는 일년 산후까지 사전 또는 산기 기간 동안 산소 및 / 또는 뇌 혈류량 부족. 또한, 염증 이제 CP의 개발에 중요한 요소가 될 것으로 생각된다. CP 사례의 대부분은 뇌실 주위 백질 연화증 (PVL)로 알려진 심실 주위 백질 손상과 연관된다. 이 신경 학적 특징은 CP로 이어지는 초기 모욕은 희소 돌기 아교 세포가 모욕에 가장 취약한 뇌 발달의 기간 동안 발생하는 것을 의미한다. 32주 임신 - 희소 돌기 아교 세포가 손상에 가장 민감한 인간의 급속한 희소 돌기 아교 세포 성장의 기간도 기간은 24 사이입니다. 설치류에 해당하는 기간은 산후 일 2 - 7 7 및 CP는이 모델에서 유도되는 경우이다. 여기에 설명 된 테스트를 수행하는 데 사용 된 CP의 신생 마우스 모델은 INJ를 만들 염증 저산소 허혈 결합더 나은 모방은 신경 퇴행 인간의 CP에서 본 것을 URY. 이 모델은 인간 환자 CP 유사한 별개의 모터 결손뿐만 아니라 별개의 백질 손상이없는 CP의 다른 동물 모델에서 관찰 된 주요 결점 중 일부를 해결한다. 동일한 모델을 사용하여 공동 작업자 이전 연구 염증 첨가 따라서 더 CP 8에서 보이는 아이들 PVL 에뮬레이션, 백질 손상을 개선하는 것이 증명 하였다. 이전 데이터를 구축,이 논문은 동물의 나이와 같은 모터 행동의 변화를 평가하기 위해 신생아 모터 테스트의 포괄적 인 배터리를 제공한다.

<table><tbody><tr><td></td><td></td><td></td><td></td></tr><tr><td>C57BL/6 mice</td><td>Charles River Laboratories</td><td>STRAIN CODE: 027&amp;nbsp;</td><td>C57BL/6NCrl is the exact strain we use</td></tr><tr><td>Anesthesia Dish, PYREX&amp;trade; Crystallizing Dish</td><td>Corning Life Sciences Glass&amp;nbsp;</td><td>3140125</td><td>Capacity: 25.03 oz. (740ml); Dia. x H: 4.92 x 2.55 in. (125 x 65mm). However, any small round glass container will work. A 2 cup capacity pyrex food storage bowl with flat bottom will also work and is much cheaper (Pyrex model number: 6017399).</td></tr><tr><td>Covered lead ring</td><td>Fisher Scientific</td><td>S90139C</td><td>Lead ring for stablizing flasks in a water bath. It is used inside the anesthesia dish.</td></tr><tr><td>Scalpel Blade #11</td><td>World Precision Instrucments, Inc.</td><td>500240</td><td></td></tr><tr><td>Small Vessel Cauterizer</td><td>Fine Science Tools</td><td>18000-00</td><td></td></tr><tr><td>Micro Hook</td><td>Fine Science Tools</td><td>10064-14</td><td></td></tr><tr><td>Vetbond Suture Glue</td><td>3M</td><td>1469SB</td><td>n-butyl cyanoacrylate adhesive</td></tr><tr><td>Lipopolysaccharide</td><td>Sigma Life Science</td><td>L4391</td><td>Lipopolysaccaride from E.coli 0111:B4, gamma irradiated</td></tr><tr><td>12 x 12 inch opaque box</td><td>Acrylic Display Manufacturing: A division of Piasa Plastics</td><td>C4022</td><td>Colored Acrylic 5-Sided Cube, 3/16&quot; Colored Acrylic, 12&quot;W x 12&quot;D x 12&quot;H;&amp;nbsp; http://www.acrylicdisplaymfg.com/html/cubes_19.html</td></tr><tr><td>Camera/camcorder</td><td>JVC</td><td>GC-PX100BUS</td><td>Any camcorder that works well in low light and can be imported and edited. We use the JVC GC-PX100 Full HD Everio Camcorder.</td></tr><tr><td>Covidien Tendersorb&amp;trade; Underpads</td><td>Kendall Healthcare Products Co</td><td>7174</td><td></td></tr><tr><td>WypAll L40</td><td>Kimberly-Clark Professional</td><td>5600</td><td>Any surface with moderate grip will do</td></tr><tr><td>Surface at 45 degree incline</td><td></td><td></td><td>We use a cardboard box.</td></tr><tr><td>Thin wire from a pipe cleaner</td><td>Creatology</td><td>M10314420</td><td>Any pipe cleaner from any craft store will work.</td></tr><tr><td>50mL conical tube</td><td>Falcon</td><td>352070</td><td></td></tr><tr><td>Fiberglass Screen Wire</td><td>New York Wire&amp;nbsp; www.lowes.com</td><td>14436</td><td>Any supplier can be used as long as their screen is 16 x 16 or 18 x 16</td></tr><tr><td>Razor blade</td><td>Fisherbrand</td><td>12-640</td><td>A wooden stick applicator or wooden part of a cotton-tipped swab will also work.</td></tr><tr><td>OPTIX 24-in x 4-ft x 0.22-in Clear Acrylic Sheet to make Clear Acrylic Walkway</td><td>PLASKOLITE INC</td><td>1AG2196A</td><td>Clear acrylic (1/8&quot; thick) with sides and a top to limit exploration. We bought a sheet of acrylic from a local hardware store and had them cut it to size. (2) 2&quot; x 2&quot;; (3) 2&quot; x 18&quot;; (1) 2&quot; x 15.5&quot;; (1) 2&quot; x 3&quot;. Using clear tape, tape all sides together, with the 15.5&quot; piece on top. Tape the 3&quot; piece to the end of the 15.5&quot; piece to create a flap/entryway for the mice. Alternatively, part or all of the walkway can be glued together, and only taping on the top pieces. This design will allow for the walkway to be opened for easy cleaning.</td></tr><tr><td>Protractor</td><td>Westscott</td><td>ACM14371</td><td></td></tr></tbody></table>

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.

마우스마다 점에 대해 서로 다른 마우스를 사용 P7 P13에 (24 시간 다음 수술) (수술 후 일주)에서 시험 하였다 그래서 테스트 패러다임을 학습하는 것은 혼란 변수가 아니었다. 마우스는이 시점에서 가장 큰 결손을 켰을 때, P8은 대표적인 결과로서 선택 하였다. 걷기에 크롤링에서 전환은 CP 신생아 마우스에서 지연된다 인간의 CP 환자는 발가락 걷기에서 scissored 걸음 걸이에 이르기까지, 걸음 걸이 이상을 가지고있다. 모델 디스플레이는 인간과 비슷한 적자를 보행이 CP로, 보행을 평가 하였다. 마우스는 직선 산책하는 동안 걸음 걸이 대칭 및 사지 발 운동 득점했다. CP 1.083 ± : 48 시간 다음 수술 (PND 8)에서, CP 마우스는 덜 대칭 사지 운동과 가짜 대응에 비해는 &quot;크롤링&quot;보행 (평균 보행 점수를했다가짜 1.639 ± 0.4859 대 0.6337, N = 12, N = 9; P &lt;0.05, 그림 10). 일주하여 CP 및 마우스 모두 가짜 (데이타 미기재) 도보로 전환했다. <img alt="그림 10" src="/files/ftp_upload/53569/53569fig10.jpg" /> 그림 10. CP 마우스 새끼 샴스뿐만 아니라 Ambulate하지 않습니다. 가짜 마우스 (검은 막대) 1.639 ± 0.4859 (N = 9), 그들의 외래 개발을 의미하는 비대칭 사지의 움직임과 느린 크롤링 사이에 폭포의 평균 점수가 있습니다. CP 마우스 (회색 막대)는 자신의 보행을 의미하는 것은 덜 개발하고, 1.083 ± 0.6337 (N = 12)의 평균 점수를 받고 비대칭 사지 운동을하는 경향이있다. 데이터는 평균 ± SEM으로 표현된다; * P &lt;0.05이다. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53569/53569fig10large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> 힌dlimb 발 각도 CP 증가된다 보행 외에도 뒷다리 발 각 평가 하였다. CP 77.48 ± 9.848, N = 9 대 가짜 54.54 ± : 평균 각도를, 8 일간짜리 가짜 마우스 새끼는 hindpaws 직선 (그림 2 걸을 때 hindpaws을 스플레이 한 HIL 마우스에 비해, 앞으로 직면 함께 산책 8.043, N = 11, P &lt;0.0001, 그림 11). 새끼가 자신의 걸음 걸이를 안정시키고 균형과 조정을 지원하기 위해 자신의 뒤쪽 발의 각도를 증가시킬 필요가 있다는 점에서이 증가 각도, 보행 불안정과 상관. <img alt="그림 11" src="/files/ftp_upload/53569/53569fig11.jpg" /> 그림 11. CP 마우스 새끼들까지 잔치 스플레이 자신의 Hindpaws 산책. CP 마우스 (검은 막대), 77.48 ± 8.043 (N = 11)의 자신의 뒷다리 사이의 평균 각도가 가짜 마우스 (회색 B 동안<html> ARS)는 54.54 ± 9.848 (평균 각도가 N = 9). 데이터는 평균 ± SEM으로 표현된다; **** p &lt;0.0001이다. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53569/53569fig11large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> CP 마우스는 적자를 표시하지 않는 경우 표면 바로 잡고 일부 CP 환자 트렁크 제어 장애 것처럼 표면 복원력 시험 (Heyrman 외., 2013)에 포함 하였다. 또한, 시스템은 바로 잡고 전정의 필요성을 검출 할 필요가 일부 환자 CP 23 전정 결손이있다. 허위 대조군과 비교시 바로 잡고 CP 마우스는 현저한 결손을 보이지 않는다 (데이터는 보이지 않음). CP 마우스는 제외 Geotaxis 테스트에서 위장과 동일하게 수행 &quot;FO : 유지-together.within 페이지 =&quot;을 t.. 1 &quot;&gt; 부정적인 geotaxis은 경 사진 표면에 내리막에 직면 장소 인에 의해 마우스에 도전하는 젊은 새끼 모터 조정을 테스트하는 데 사용 적자를 나타낼 수 동양 오르막에 지연 또는 실패한다 (데이터 미도시) 가짜 마우스에 비해 마이너스 geotaxis와 도전 때 조정, 밸런스, 전정 입력한다. CP 마우스가 더 결손을 표시하지 않는다. 또한, CP 마우스 다시 배향 서로 비교 한쪽으로 설정하는 선호를 보이지 않았다 . 전면 사지 서스펜션 테스트는 10 일 이상 마우스에 적합하다 CP 환자는 파악 미세 운동 능력, 근육의 톤과 적자 감소했다. 이 마우스 모델에서 약점을 테스트하기 위해, 우리는 전면 사지 서스펜션 테스트를 사용했다. 또한,이 모델은 일방적 인 허혈 손상 및 양면 - 다움이 정지 테스트를 사용하여 측정 할 수 사용합니다. 이 테스트십일 15 세 이상 마우스에 대한 더 낫다. 팔일 이전에, 부상으로 다음과 같은 두 가지 일, CP와 가짜 쥐 사이에 유의 한 차이가 없었다 (데이터는 도시하지 않음). 뒷다리 힘 CP 마우스에 감소 인간의 CP 환자는 종종 인해 모터 제어와 힘의 부족으로 중괄호 또는 보조 산책 장치가 필요합니다. 인간 설치류 CP 모델과 비교하기 위해, 뒷다리 강도는 뒷다리 현탁액 시험을 사용하여 평가 하였다. CP 3.468 ± 0.5561, N = 13 대 가짜 3.891 ± 0.1329, N = 13, P는 &lt;: 원뿔 튜브의 측면에서 정지 할 때 점수를 걸려에서 감소에 의해 입증 된 바와 같이, CP 마우스는 뒷다리 매달려 점수 (사지 약점을 보였다 0.05,도 12). 차이가 뒷다리 정지 시간에 관찰되지 않았다 (데이터는 보이지 않음). 따라서, CP 인간 환자와 마찬가지로, CP 생쥐 hindl을 보여IMB (다리) 약점. <img alt="그림 12" src="/files/ftp_upload/53569/53569fig12.jpg" /> 그림 12. 위장 마우스는 가짜 마우스 (검은 색 막대) 더 사지 분리, 따라서 강한 뒷다리 자세를 보여 3.891 ± 0.1329의 평균 매달려 점수에서. 약간 있지만 (N = 13) CP 마우스보다 자신의 뒷발에 크게 강화된다 3.468 ± 0.5561 (N = 13)의 평균 매달려 점수와 CP 마우스 (회색 막대)보다 튜브의 가장자리에 매달려 때. 데이터는 평균 ± SEM으로 표현된다; * P &lt;0.05이다. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53569/53569fig12large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> 그립의 강도 다음은 CP 부상 감소 네 발에 파악하는 것은 설치류에서 중요하다등반 및 평평하지 않은 표면에 걸쳐 실행의 측면. 그립 주로 자릿수 오히려 손재주 또는 선형 힘보다 현저한 지속적인 힘이 필요하며 24 발. 마우스를 반전 와이어 메쉬 스크린 상에 자신의 체중을 유지하도록 요구되었다. CP 마우스는 자신의 그립을 유지하지 못한 이들 마우스는 상당히 낮은 각도로 떨어졌다 (사 사지 평균 각도 : CP 75.627 ± 24.48, N = 11 대 가짜 96.57 ± 10.836, N = 9; P &lt;0.05, 그림 13). 이 데이터는 CP 생쥐 악력이 크게 부족이 있다는 것을 나타낸다. <img alt="그림 13" src="/files/ftp_upload/53569/53569fig13.jpg" /> 그림 13. CP 마우스는 샴스보다 약한 그립이 있습니다. 96.57 ± 10.836의 평균 반전 각도로 파악할 수 가짜 마우스 (검은 막대) (N = 9). CP 마우스 (회색 표시 줄) 만 75.627 ± 24.48 (N = 11)의 반전 각도에 도달 할 수 있습니다. 데이터는 평균 ± SEM으로 표현된다; * 페이지입니다0; 0.05. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53569/53569fig13large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> 파지 반사의 적자는 CP 마우스에 명백한 있습니다 총 모터 적자와 함께, 미세 운동의 움직임 또한 CP 환자 25, 26에 손상됩니다. 인간의 파악 반사는 출생시 존재하고 약 5 사라 - 6개월. 그러나, 과장 속도 또는 파지의 강도, 파악 실패, 또는 ​​생후 6 개월 후 파악 반사의 재 출현으로 파악 반사의 변화는 모두 신경계에 손상을 나타냅니다. 공산당 모델에 쥐고 비교하기 위해 재귀 파지 적자가 결정되었다. 손상 후 48 시간에서, CP의 마우스 파지 반사의 감소를 입증 (평균 발을 파악48 시간에서 : CP 2.429 ± 0.9376, N = 14 대 3.214 ± 0.8018 가짜, N = 14; p &lt;0.05,도 14A). 앞발에 오른쪽 발 환경 설정에 약간 있지만 중요하지 증가가 발생했습니다 (데이터는 도시하지 않음). 거기 hindpaws에 상당한 오른쪽 발 선호했다 (CP 75.0 ± 42.74는 N = 14, 가짜 17.86 ± 54.09 대, N = 14, P &lt;0.005, 그림 14B). 더 주목할만한 발 바람직하다; : 일주일 손상 후, CP 마우스는 파악 적자 (그림 14C, P &lt;0.05 CP 2.75 ± 1.035을, N = 8, 가짜 3.80 ± 0.6325 대, N = 10 평균 발 1 주에 파악) 표시 . <img alt="그림 14" src="/files/ftp_upload/53569/53569fig14.jpg" /> 그림 14. CP 마우스는 부상 뇌 지역에 반대쪽 Hindpaws에서 파악하는 적자를 보유하고 있습니다. (A) 48 시간 다음의 부상 (PND 8), CP 마우스 (회색 막대) 평균과 막대기를 파악, 가짜 애니 마보다 적은 발LS (검은 색 막대). (B) CP 마우스 (회색 막대가) 왼쪽 뒷발 (상해 동측)을 사용하는 것이 아니라 (부상 반대측) 오른쪽 뒷발로 파악하기위한 환경 설정을 표시합니다. 가짜 마우스 (검은 색 막대)이 오른쪽 발 환경 설정을 표시하지 않습니다. 오른쪽 발 기본 설정은 다음과 같이 계산된다 ([오른쪽 발 - 발 왼쪽] / [오른쪽 발 + 왼쪽 발 + 모두 발] * 100) (C) 1 주에 다음과 같은 부상, CP 마우스 (회색 막대)에 비해 여전히 적자를 파악 보여줍니다. 가짜 (검은 막대). 데이터는 평균 ± SEM으로 표현된다; * ** p &lt;0.005, P &lt;0.05이다. <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/53569/53569fig14large.jpg" target="_blank">이 그림의 더 큰 버전을 보려면 여기를 클릭하십시오.</a> CP 마우스는 절벽 회피 동안 떨어져 가장자리에서 설정 절벽 회피 시험은 아를 설정하는 쥐의 고유 두려움에 의존안전을 향해 가파른 절벽과 머리에서 y를. 일부 CP 환자 전정 장애,뿐만 아니라 손상된 모터 제어가되지만, CP 마우스는이 시험의 모든 결핍을 보여주지 않았다.

Watch this Scientific Journal Video about A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy at JoVE.com

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

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.

뇌성 마비의 신생아 마우스 모델에서 모터 테스트의 배터리

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-battery-of-motor-tests-in-a-neonatal-mouse-model-of-cerebral-palsy

Universidad San Sebastian

Research

JoVE Journal

Medicine

24.0K 조회수.  Lewiz Katz School of Medicine at Temple University. 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.

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

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

파킨슨 병의 마우스 모델에서 감각 기능의 평가

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

연구

행동분석학

Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore by rearing and touching the walls of the cylinder with their forelimb paws for postural support. Following ischemic injury to the forelimb sensorimotor cortex, rats rely more heavily on their unaffected forelimb paw for postural support resulting in fewer touches with their affected paw which is termed forelimb asymmetry. In contrast, focal ischemic damage in the mouse brain fails to result in comparable consistent deficits in forelimb asymmetry. While forelimb asymmetry deficits are infrequently observed, mice do demonstrate a novel behaviour post stroke termed &#8220;paw-dragging&#8221;. Paw-dragging is the tendency for a mouse to drag its affected paw along the cylinder wall rather than directly push off from the wall when dismounting from a rear to a four-legged stance. We have previously demonstrated that paw-dragging behaviour is highly sensitive to small cortical ischemic injuries to the forelimb motor cortex. Here we provide a detailed protocol for paw-dragging analysis. We define what a paw-drag is and demonstrate how to quantify paw-dragging behaviour. The cylinder test is a simple and inexpensive test to administer and does not require pre-training or food deprivation strategies. In using paw-dragging analysis with the cylinder test, it fills a niche for predicting cortical ischemic injuries such as photothrombosis and Endothelin-1 (ET-1)-induced ischemia &#8211; two models that are ever-increasing in popularity and produce smaller focal injuries than middle cerebral artery occlusion. Finally, measuring paw-dragging behaviour in the cylinder test will allow studies of functional recovery after cortical injury using a wide cohort of transgenic mouse strains where previous forelimb asymmetry analysis has failed to detect consistent deficits.

Classical forelimb asymmetry analysis of the cylinder test is routinely used to assess behavioural deficits in rats following brain injury or stroke; however, it fails to detect consistent deficits in mice. This study demonstrates that quantifying paw-dragging behaviour is a more sensitive analysis of brain injury in mice.

발 - 드래그 : 소설, 마우스 실린더 시험의 민감성 분석

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore ...

Measuring Motor Coordination in Mice

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance2. 
Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available.
The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. 
Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test12 or the Catwalk (Noldus)15 apparatus are generally used to assess motor coordination in rats.

Protocols are presented for two established motor coordination tasks, the accelerating rotarod and horizontal bar, also two tests developed in Oxford recently, the static rods and parallel bars. These tests can detect motor impairments potentially of interest in their own right, as well as being possible variables in tests of other areas of behavior.

마우스에 모터 조정을 측정

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such ...

신경과학

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.

신생아 쥐 새끼들까지 잔치에서 신경 발달 반사 테스트

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

Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the animal&#39;s wellbeing and health. There are numerous behavioral tests that may be applied. We selected a test for general locomotion, the open field test (OFT); a test for muscular strength, the mesh test (MT); and a test for coordination, the rotarod test (RR). Testing can be accomplished on a weekly or monthly basis. As a test for general locomotion, the OFT works by objectively monitoring movement parameters while the mouse is in an open field apparatus. The field is generally a 2&#39; x 2&#39; box, and the movements are recorded through laser sensing or through video capture. The mouse is placed in the center of the open field and allowed to move freely for the test. The MT uses the latency for a mouse to fall off an inverted screen as a measure of muscular strength. A mouse is placed on a screen, which is inverted over a clear box, and is timed for their latency to fall. Three trials are performed, with the best of the three trials scored for that day. A score of 60 s is the maximum time a mouse is left inverted. Mice are given a 5-min rest period between mesh test trials. Lastly, an accelerated protocol on the RR assesses motor coordination and endurance. During a trial, a mouse walks on a rotating rod as it increases in speed from 4 rpm to 40 rpm over 5 min. The trial ends when the mouse touches the magnetized pressure sensor upon falling. Each mouse undergoes three trials, and the best trial is scored for that day. This combined behavioral data allows for the global assessment of mobility, coordination, strength, and movement of the test animals. At least two out of the three behavioral testing measures must show improvement for an animal to qualify as having overall improved motor function.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects of a disease or treatment on an animal's wellbeing. In order to globally assess motor functioning, we selected tests for general locomotion, muscular strength, and coordination: the open field test, the mesh test, and the rotarod test, respectively.

행동의 배터리 테스트 사정 일반 운동, 근육 강도, 그리고 조정 마우스

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the ...

A Neonatal Mouse Spinal Cord Compression Injury Model

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1.

This article describes a method for generating a reproducible spinal cord compression injury (SCI) in the neonatal mouse. The model provides an advantageous platform for studying mechanisms of adaptive plasticity that underlie spontaneous functional recovery.

신생아 마우스 척수 압축 부상 모델

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal ...

의학

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

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 brain injury by studying neurobehavioral functions in these mice compared to non-operated (i.e., normal) mice. During the study, Rice-Vannucci&#39;s method was used to induce neonatal HI brain damage in postnatal day 7-10 (P7-10) mice. The HI operation was performed on the pups by unilateral carotid artery ligation and exposure to hypoxia (8% O2 and 92% N2 for 90 min). One week after the operation, the damaged brains were evaluated with the naked eye through the semi-transparent skull and were categorized into subgroups based on the absence (&#34;no cortical injury&#34; group) or presence (&#34;cortical injury&#34; group) of cortical injury, such as a lesion in the right hemisphere. On week 6, the following neurobehavioral tests were performed to evaluate the cognitive and motor functions: passive avoidance task (PAT), ladder walking test, and grip strength test. These behavioral tests are helpful in determining the effects of neonatal HI brain injury and are used in other mouse models of neurodegenerative diseases. In this study, neonatal HI brain injury mice showed motor deficits that corresponded to right hemisphere damage. The behavioral test results are relevant to the deficits observed in human neonatal HI patients, such as cerebral palsy or neonatal stroke patients. In this study, a mouse model of neonatal HI brain injury was established and showed different degrees of motor deficits and cognitive impairment compared to non-operated mice. This work provides basic information on the HI mouse model. MRI images demonstrate the different phenotypes, separated according to the severity of brain damage by motor and cognitive tests.

We performed unilateral carotid artery occlusion on postnatal day 7-10 CD-1 mouse pups to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of HI brain injury. We studied neurobehavioral functions in these mice compared to non-operated normal mice.

신생아 Hypoxic-허 혈 성 뇌 손상의 마우스 모델에서 Neurobehavioral 평가

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 ...

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.

신생아 Polymicrobial 패 혈 증에 대 한 제어 마우스 모델

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

면역학 및 감염병학

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal neurological deficits and even amnesia. Athletes participating in contact sports are at high risk of exposure to large number of mTBIs. In terms of the level of injury in a sporting athlete, a mTBI is defined as a mild injury that does not cause gross pathological changes, but does cause short-term neurological deficits that are spontaneously resolved. Despite previous attempts to model mTBI in mice and rats, many have reported gross adverse effects including skull fractures, intracerebral bleeding, axonal injury and neuronal cell death. Herein, we describe our highly reproducible animal model of mTBI that reproduces clinically relevant symptoms. This model uses a custom made pneumatic impactor device to deliver a closed-head trauma. This impact is made under precise velocity and deformation parameters, creating a reliable and reproducible model to examine the mechanisms that contribute to effects of single or repetitive concussive mTBI.

Athletes absorb several hundred mild traumatic brain injuries (mTBI)/concussions every year; however, the consequence of these on the brain is poorly understood. Therefore, an animal model of single and repetitive mTBI that consistently replicates clinically relevant symptoms provides the means to advance the study of mTBI and concussion.

단일 및 반복적 인 경미한 외상성 뇌 손상의 마우스 모델

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal ...

MouseWalker를 사용한 척수 손상 마우스의 운동 기능 장애 정량화

Using the MouseWalker to Quantify Locomotor Dysfunction in a Mouse Model of Spinal Cord Injury

The execution of complex and highly coordinated motor programs, such as walking and running, is dependent on the rhythmic activation of spinal and supra-spinal circuits. After a thoracic spinal cord injury, communication with upstream circuits is impaired. This, in turn, leads to a loss of coordination, with limited recovery potential. Hence, to better evaluate the degree of recovery after the administration of drugs or therapies, there is a necessity for new, more detailed, and accurate tools to quantify gait, limb coordination, and other fine aspects of locomotor behavior in animal models of spinal cord injury. Several assays have been developed over the years to quantitatively assess free-walking behavior in rodents; however, they usually lack direct measurements related to stepping gait strategies, footprint patterns, and coordination. To address these shortcomings, an updated version of the MouseWalker, which combines a frustrated total internal reflection (fTIR) walkway with tracking and quantification software, is provided. This open-source system has been adapted to extract several graphical outputs and kinematic parameters, and a set of post-quantification tools can be to analyze the output data provided. This manuscript also demonstrates how this method, allied with already established behavioral tests, quantitatively describes locomotor deficits following spinal cord injury.

저자 스포트라이트: MouseWalker를 사용하여 척수 손상 마우스 모델에서 운동 기능 장애 정량화  

An experimental pipeline to quantitatively describe the locomotor pattern of freely walking mice using the MouseWalker (MW) toolbox is provided, ranging from initial video recordings and tracking to post-quantification analysis. A spinal cord contusion injury model in mice is employed to demonstrate the usefulness of the MW system.