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>
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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. 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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. 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The authors declare that they have no competing financial interests.

Utilizzando modelli animali per studiare le malattie umane è rilevante solo se vi è sovrapposizione tra la risposta cellulare e molecolare tra uomo e roditori e che i test comportamentali eseguiti hanno rilevanza diretta per i sintomi umani. Uno dei principali problemi con gli studi sulle malattie pediatriche è che molti ricercatori utilizzano roditori adulti per creare il modello, così come la valutazione del comportamento degli adulti roditore, senza considerare le differenze di sviluppo che possono essere importanti per il processo della malattia. A causa di questi problemi, è importante che la ricerca sull&#39;uso malattia pediatrica non solo la rettificato di sviluppo time-punti appropriata (ad esempio, lo sviluppo del sistema nervoso centrale umano a 28 - 32 settimane è equivalente ad un giorno post-natale 2-7 giorni roditore) 7, ma anche test comportamentali che esamineranno motore del caso, i comportamenti di sviluppo sensoriali o riflessivi. Così, come si sviluppa ogni nuovo modello di malattia neonatale, deve essere rigorosamente testati per assicurare che il cellularee risposte comportamentali forniranno i dati traducibili più adeguati tra roditori e umana. La paralisi cerebrale è un disturbo del motore, che persistono in età adulta. Un problema con molti dei modelli paralisi cerebrale disponibili oggi è la mancanza di ripetibile, test motore normalizzato in grado di correlare con i deficit osservati in pazienti pediatrici. In questo nuovo modello, che unisce ipossia, ischemia e infiammazione in un mouse neonatale, comportamento motorio è stata valutata utilizzando una serie di test specifici per topi neonati. Per ridurre la soggettività e aumentare la segnalazione quantitativa, diverse prove sono state modificate per includere molto specifica, ma facile valutare misure che possono essere standardizzati. Inoltre, le valutazioni anteriori e arti posteriori possono essere eseguiti separatamente, e le differenze sinistra / destra può essere determinato. Questa batteria di test è specifico per topi neonati fino a due settimane di età. Questo modello CP dimostradifficoltà nel camminare (deambulazione, angolo del piede degli arti posteriori), nonché la debolezza specifici degli arti (sospensione di quattro arti, la sospensione degli arti posteriori), e deficit in riflessi di sviluppo (afferrare reflex). Anche se in questo studio solo un timepoint stato esaminato, questi deficit possono essere monitorati nel corso del tempo. Ci sono altre batterie di test che possono essere utilizzati sul neonato, come ad esempio la batteria del Fox di test o di valutazione di 15 tappe dello sviluppo di Heyser. Tuttavia, questi test confrontare il neonato all&#39;adulto, il cui risposte non può essere lo stesso, perché il neonato è ancora in via di sviluppo. La batteria di Fox e test assement di Heyser si basano su informazioni soggettive osservazionale con dicotomico valutazione (sì o no), piuttosto che dati oggettivi (angolo, postura basati sulla forza, ecc). A causa della soggettività di questi test, molti scienziati si sono adattati, aggiunto o rimosso criteri, rendendo così i loro risultati incomparabili agli altri e limiteing l&#39;utilità dei dati in termini di stabilire un deficit di base per una particolare malattia o disturbo. Attraverso la creazione di una serie di test standardizzati a motore che sono qualitative e specificamente progettato per testare i neonati, i risultati dei singoli gruppi di ricerca possono essere preciso e affidabile segnalati e confrontati.

Lo sviluppo di nuovi modelli di infortunio o di malattia pediatrica utilizzando roditori è spesso difficile a causa della sorprendente capacità di entrambi i ratti e topi di recuperare rapidamente da lesioni neurologiche. Pertanto, al fine di convalidare qualsiasi nuovo modello di malattia pediatrica, accuratamente esaminando i cambiamenti cellulari e molecolari devono andare di pari passo con esiti comportamentali. In molti modi, il recupero comportamentale funzionale può essere più importante di cambiamenti cellulari sottostanti in termini di rilevanza terapeutica e traslazionale. Come i ricercatori saperne di più sulla ferita nell&#39;adulto e nel neonato, è chiaro che le loro risposte sono molto diversi e non possono essere estrapolati tra i due. Ad esempio, i topi neonati mostrano diversi livelli di fattore di crescita nervoso, fattore neurotrofico derivato dal cervello, neurotrofina-3 e gliali fattore neurotrofico delle cellule linea di derivazione dopo un trauma del midollo spinale 1,2. Inoltre, i neonati hanno una significativa perdita di barriera emato-encefalica dopo l&#39;ictus 3, demonstrate corticale riassetto neurone dopo periferici lesione del nervo 4, e hanno un astrogliosis ritardato o rallentato in seguito a lesione del midollo spinale e ipossia-ischemia 5,6. Pertanto, è importante che traslazionale ricerca pediatrica utilizzare modelli evolutivamente equivalenti e che tali modelli vengono valutati per entrambi i cambiamenti cellulari / molecolari e test comportamentali adatti alla loro età. Paralisi cerebrale (CP) è un disturbo motorio che colpisce 3: 1000 nati vivi ogni anno (NIH). I bambini con CP presentano una gamma di sintomi e patologie associate, a seconda della gravità della malattia. Difficoltà con il movimento e il coordinamento sono i segni più comuni, insieme a ritardi nel raggiungimento del motore tappe dello sviluppo. Altri segni includono tono muscolare anormale (sia aumentato o diminuito), ridotta capacità motorie, difficoltà a camminare, sbavando eccessiva e la deglutizione, e ritardi del linguaggio (NIH). La causa di fondo di CP si crede di essereuna mancanza di ossigeno e / o il flusso di sangue al cervello durante il periodo di pre o peri-parto, o fino a un anno post-partum. Inoltre, l&#39;infiammazione è ora ritenuta un componente chiave nello sviluppo di CP. La maggioranza dei casi di CP sono associati con il bianco danno la materia intorno ai ventricoli, noto come leucomalacia periventricolare (PVL). Questa caratteristica neurologica suggerisce che l&#39;insulto iniziale che porta al CP si verifica durante il periodo di sviluppo del cervello quando i oligodendrociti sono più vulnerabili agli insulti. Il periodo di crescita rapida degli oligodendrociti in un essere umano, anche il periodo in cui gli oligodendrociti sono i più sensibili al danno, è tra i 24 - 32 settimane di gestazione. Nel roditore, il periodo equivalente è giorni post-natale 2 - 7 7, ed è quando CP è indotta in questo modello. Il modello di topo neonatale di CP che è stato utilizzato per effettuare i test descritti qui combina ipossia e ischemia con l&#39;infiammazione di creare un injury che imita meglio la neurodegenerazione visti in CP umana. Questo modello affronta alcune delle principali carenze riscontrate in altri modelli animali di CP, che mancano di deficit motori distinti che assomiglia pazienti in CP umani, così come distinta danni sostanza bianca. Precedenti studi da un collaboratore utilizzando lo stesso modello hanno dimostrato che l&#39;aggiunta di infiammazione aumenta il danno sostanza bianca, così meglio emulare il PVL osservati nei bambini con CP 8. Sulla base dei dati precedenti, questo documento presenta una serie completa di test del motore neonatali al fine di valutare i cambiamenti nel comportamento del motore, come l&#39;età degli animali.

<table border="0" cellpadding="0" cellspacing="0" width="1354">
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">C57BL/6 mice</td>
			<td style="width:239px;">Charles River Laboratories</td>
			<td style="width:103px;">STRAIN CODE: 027&#160;</td>
			<td style="width:741px;">C57BL/6NCrl is the exact strain we use</td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:271px;">Anesthesia Dish, PYREX&#8482; Crystallizing Dish</td>
			<td style="width:239px;">Corning Life Sciences Glass&#160;</td>
			<td style="width:103px;">3140125</td>
			<td style="width:741px;">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 height="20">
			<td height="20" style="height:20px;width:271px;">Covered lead ring</td>
			<td style="width:239px;">Fisher Scientific</td>
			<td style="width:103px;">S90139C</td>
			<td style="width:741px;">Lead ring for stablizing flasks in a water bath. It is used inside the anesthesia dish.</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Scalpel Blade #11</td>
			<td style="width:239px;">World Precision Instrucments, Inc.</td>
			<td style="width:103px;">500240</td>
			<td style="width:741px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Small Vessel Cauterizer</td>
			<td style="width:239px;">Fine Science Tools</td>
			<td style="width:103px;">18000-00</td>
			<td style="width:741px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Micro Hook</td>
			<td style="width:239px;">Fine Science Tools</td>
			<td style="width:103px;">10064-14</td>
			<td style="width:741px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Vetbond Suture Glue</td>
			<td style="width:239px;">3M</td>
			<td style="width:103px;">1469SB</td>
			<td style="width:741px;">n-butyl cyanoacrylate adhesive</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Lipopolysaccharide</td>
			<td style="width:239px;">Sigma Life Science</td>
			<td style="width:103px;">L4391</td>
			<td style="width:741px;">Lipopolysaccaride from e.coli 0111:B4, gamma irradiated</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:271px;">12x12 inch opaque box</td>
			<td style="width:239px;">Acrylic Display Manufacturing: A division of Piasa Plastics</td>
			<td style="width:103px;">C4022</td>
			<td>Colored Acrylic 5-Sided Cube, 3/16&#34; Colored Acrylic, 12&#34;W x 12&#34;D x 12&#34;H;&#160; http://www.acrylicdisplaymfg.com/html/cubes_19.html</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:271px;">Camera/camcorder</td>
			<td style="width:239px;">JVC</td>
			<td style="width:103px;">GC-PX100BUS</td>
			<td style="width:741px;">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 height="20">
			<td height="20" style="height:20px;width:271px;">Covidien Tendersorb&#8482; Underpads</td>
			<td style="width:239px;">Kendall Healthcare Products Co</td>
			<td style="width:103px;">7174</td>
			<td style="width:741px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">WypAll L40</td>
			<td style="width:239px;">Kimberly-Clark Professional</td>
			<td style="width:103px;">5600</td>
			<td style="width:741px;">Any surface with moderate grip will do</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Surface at 45 degree incline</td>
			<td style="width:239px;"></td>
			<td style="width:103px;"></td>
			<td style="width:741px;">We use a cardboard box.</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Thin wire from a pipe cleaner</td>
			<td style="width:239px;">Creatology</td>
			<td style="width:103px;">M10314420</td>
			<td style="width:741px;">Any pipe cleaner from any craft store will work.</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">50mL conical tube</td>
			<td style="width:239px;">Falcon</td>
			<td style="width:103px;">352070</td>
			<td style="width:741px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Fiberglass Screen Wire</td>
			<td style="width:239px;">New York Wire&#160; www.lowes.com</td>
			<td style="width:103px;">14436</td>
			<td style="width:741px;">Any supplier can be used as long as their screen is 16x16 or 18x16</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:271px;">Razor blade</td>
			<td style="width:239px;">Fisherbrand</td>
			<td style="width:103px;">12-640</td>
			<td style="width:741px;">A wooden stick applicator or wooden part of a cotton-tipped swab will also work.</td>
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			<td height="100" style="height:100px;width:271px;">OPTIX 24-in x 4-ft x 0.22-in Clear Acrylic Sheet to make Clear Acrylic Walkway</td>
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			<td style="width:741px;">Clear acrylic (1/8&#34; 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&#34;x2&#34;; (3) 2&#34;x 18&#34;; (1) 2&#34;x15.5&#34;; (1) 2&#34;x3&#34;. Using clear tape, tape all sides together, with the 15.5&#34; piece on top. Tape the 3&#34; piece to the end of the 15.5&#34; 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 height="20">
			<td height="20" style="height:20px;width:271px;">Protractor</td>
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</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.

I topi sono stati testati da P7 (24 ore dopo l&#39;intervento chirurgico) a P13 (1 settimana dopo l&#39;intervento chirurgico), usando i mouse diverso per ogni time-point in modo che l&#39;apprendimento di una paradigma di test non era una variabile di confondimento. P8 è stato selezionato come risultati rappresentativi, come topi hanno mostrato i maggiori deficit a questo punto di tempo. Transizione da Crawling a piedi è ritardato di CP topi neonati pazienti in CP umani hanno anomalie dell&#39;andatura, che vanno dalla punta di piedi per un&#39;andatura scissored. Dato che questo modello CP display andatura deficit simili agli esseri umani, la deambulazione è stata valutata. I topi sono stati lanciati sulla simmetria andatura e il movimento degli arti-zampa durante una passeggiata retta. A 48 ore dopo l&#39;intervento chirurgico (PND 8), i topi CP avevano meno movimento simmetrico arto e una &quot;strisciante&quot; andatura rispetto alle loro controparti sham (punteggio medio deambulazione: CP 1.083 ±0,6337, n = 12 vs sham 1.639 ± 0,4859, n = 9; p &lt;0.05, Figura 10). In una settimana, sia CP e topi sham sono passati a camminare (dati non riportati). <img alt="Figura 10" src="/files/ftp_upload/53569/53569fig10.jpg" /> Figura 10. CP mouse Pups non Ambulate così come Shams. Topi Sham (barra nera) hanno un punteggio medio di 1.639 ± 0,4859 (n = 9), vale a dire il loro sviluppo ambulatoriale cade tra il movimento degli arti asimmetrica e lento strisciare. topi CP (barra grigia) ricevono un punteggio medio di 1.083 ± 0,6337 (n = 12), il che significa la loro deambulazione è meno sviluppata e tendono ad avere il movimento degli arti asimmetrica. I dati sono espressi come media ± SEM; * È p &lt;0.05. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53569/53569fig10large.jpg" target="_blank">Cliccate qui per vedere una versione più grande di questa figura.</a> HinAngolo del piede dlimb è aumentata in CP Oltre alla deambulazione, degli arti posteriori piede ad angolo è stata valutata. Otto giorni di età cuccioli farsa del mouse a piedi con i loro hindpaws rivolto in avanti, rispetto ai topi HIL, che hanno divaricate hindpaws quando si cammina in linea retta (figura 2; angolo medio: CP 77.48 ± 9,848, n = 9, vs sham 54.54 ± 8,043, n = 11; p &lt;0,0001, Figura 11). Questo aumento dell&#39;angolo correla con instabilità andatura, dal fatto che i cuccioli bisogno di aumentare l&#39;angolo di loro zampe posteriori per stabilizzare la loro andatura e assistere con equilibrio e coordinazione. <img alt="Figura 11" src="/files/ftp_upload/53569/53569fig11.jpg" /> Figura 11. CP mouse Pups Splay loro hindpaws quando si cammina. Topi CP (barre nere) hanno un angolo medio tra i loro arti posteriori di 77.48 ± 8,043 (n = 11), mentre i topi sham (grigio b<html> ars) hanno un angolo medio di 54,54 ± 9,848 (n = 9). I dati sono espressi come media ± SEM; **** È p &lt;0,0001. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53569/53569fig11large.jpg" target="_blank">Cliccate qui per vedere una versione più grande di questa figura.</a> I topi CP Non mostrare deficit quando Righting Surface Il test di superficie di raddrizzamento è stato incluso come alcuni pazienti CP hanno alterato controllo del tronco (Heyrman et al., 2013). Inoltre, il sistema vestibolare è necessario rilevare la necessità di raddrizzamento e ci sono deficit vestibolari in alcuni pazienti CP 23. topi CP non mostrano deficit significativi quando raddrizzamento rispetto ai controlli sham (dati non riportati). I topi CP Eseguire la stessa come Sham in negativo geotassi Testing t &quot;fo: keep-together.within-page =&quot; 1 &quot;&gt; geotassi negativo è usato per testare la coordinazione motoria nei giovani cuccioli I topi sono in discussione da essere posto in discesa su una superficie inclinata ritardo o mancata salita orientare potrebbe indicare deficit.. in coordinazione, equilibrio, o ingresso vestibolare. topi CP non mostrano deficit quando provocati con geotassi negativi rispetto ai topi sham (dati non riportati). Inoltre, i topi CP non hanno mostrato una preferenza per girare verso un lato rispetto ad un altro, quando ri-orientamento . Front-Limb test sospensione è opportuna per topi anziani di 10 giorni pazienti in CP sono diminuiti del tono muscolare e deficit nelle abilità motorie, come afferrare. Per verificare la debolezza di questo modello di topo, abbiamo usato un test di sospensione anteriore degli arti. Inoltre, questo modello utilizza danno ischemico unilaterale e retro-ness potrebbero essere determinati con questo test sospensione. Questo testè meglio per i topi di età superiore ai 10 giorni 15. A 8 giorni, due giorni dopo un trauma, non vi erano differenze significative tra CP e topi sham (dati non riportati). Forza arti posteriori è diminuito nei topi CP pazienti in CP umani hanno spesso bisogno di parentesi graffe o dispositivi di assistenza a piedi a causa della mancanza di controllo del motore e forza. Al fine di confrontare il modello CP roditore per gli esseri umani, la forza degli arti posteriori è stata valutata utilizzando il test di sospensione degli arti posteriori. Quando sospeso dal lato di un tubo conico, topi CP hanno mostrato la debolezza degli arti posteriori, come dimostrato da una diminuzione della appeso punteggio (arti posteriori punteggio appeso: CP 3.468 ± 0,5561, n = 13, vs sham 3,891 ± 0,1329, n = 13; p &lt; 0,05, Figura 12). Nessuna differenza è stata osservata nel tempo di sospensione hindlimb (dati non mostrati). Così, simile a pazienti in CP umani, topi CP dimostrano hindlIMB (gamba) debolezza. <img alt="Figura 12" src="/files/ftp_upload/53569/53569fig12.jpg" /> Figura 12. I topi Sham sono leggermente ma significativamente più forte nelle loro arti posteriori rispetto ai topi CP. In un punteggio impiccagione di 3,891 ± 0,1329 (n = 13), i topi sham (barra nera) mostrano la separazione più degli arti posteriori, e quindi una più forte presa di posizione degli arti posteriori, quando appeso al bordo di un tubo di topi CP (barra grigia) con un voto medio impiccagione di 3.468 ± 0,5561 (n = 13). I dati sono espressi come media ± SEM; * È p &lt;0.05. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53569/53569fig12large.jpg" target="_blank">Cliccate qui per vedere una versione più grande di questa figura.</a> Grip forza è diminuita Following CP Injury Afferrando con tutte e quattro le zampe è importante per un roditoretermini di arrampicata e correre su superfici irregolari. Grip richiede notevole forza sostenuta, invece di destrezza o forza lineare, soprattutto nelle cifre e zampe 24. I topi sono stati tenuti a tenere il loro peso corporeo su uno schermo di rete metallica rovesciata. Topi CP non sono stati in grado di mantenere la loro presa e questi topi è sceso ad angolo significativamente più bassi (quattro arti angolo medio: CP 75,627 ± 24,48, n = 11, vs sham 96.57 ± 10.836, n = 9; p &lt;0.05, figura 13). Questi dati mostrano che vi è un deficit significativo nella forza di presa in topi CP. <img alt="Figura 13" src="/files/ftp_upload/53569/53569fig13.jpg" /> Figura 13. I topi hanno CP Grip più debole rispetto Shams. Topi Sham (barra nera) può afferrare un angolo invertito media di 96.57 ± 10,836 (n = 9). topi CP (barra grigia) possono raggiungere solo un angolo rovesciata di 75,627 ± 24.48 (n = 11). I dati sono espressi come media ± SEM; * È p0; 0.05. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53569/53569fig13large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> I deficit Grasping Reflex sono evidenti nei topi CP Insieme con deficit motorie, movimenti motorie sono anche compromesse nei pazienti CP 25,26. Il riflesso cogliere nell&#39;uomo è presente alla nascita e scompare intorno 5-6 mesi. Tuttavia, i cambiamenti riflesso di presa, quali velocità esagerata o la forza di afferramento, mancata afferrare o il riemergere del riflesso afferrare dopo 6 mesi di età, tutti indicano danni al sistema nervoso. Per confrontare afferrare nel modello CP, i deficit di presa riflessivi sono stati determinati. A 48 ore dopo l&#39;infortunio, topi CP dimostrano una diminuzione nel cogliere il riflesso (zampe medie coltein 48 ore: CP 2.429 ± 0,9376, n = 14, vs sham 3.214 ± 0,8018, n = 14; p &lt;0.05, Figura 14A). C&#39;era una leggera, ma non significativo aumento destra preferenza zampa nelle zampe anteriori (dati non riportati). C&#39;è stata una significativa preferenza zampa destra nelle hindpaws (CP 75,0 ± 42,74, n = 14, vs sham 17.86 ± 54.09, n = 14; p &lt;0.005, Figura 14B). Una settimana dopo l&#39;infortunio, topi CP mostrano deficit di presa (zampe medie colte a 1 settimana: CP 2.75 ± 1.035, n = 8, vs sham 3,80 ± 0,6325, n = 10; p &lt;0.05, Figura 14C), senza preferenza zampa notevole . <img alt="Figura 14" src="/files/ftp_upload/53569/53569fig14.jpg" /> Figura 14. I topi CP hanno deficit afferrare, nella hindpaws, controlaterale alla Cervello Regione feriti. (A) 48 ore dopo un trauma (PND 8), i topi CP (barra grigia) afferrare un bastone con, in media, un minor numero di zampe di farsa animaLS (barra nera). topi (B) CP (barra grigia) mostrano una preferenza per afferrare con la hindpaw destra (controlaterale alla lesione) in contrasto con il hindpaw sinistra (omolaterale al danno). topi Sham (barra nera) Non visualizzare questo diritto preferenza zampa. Preferenza zampa destra è calcolato come ([zampa destra - sinistra zampa] / [zampa destra + zampa sinistra + entrambe le zampe] * 100) (C) Una settimana dopo un trauma, i topi CP (barra grigia) mostrano ancora afferrare deficit rispetto al. Shams (barra nera). I dati sono espressi come media ± SEM; * È p &lt;0.05, ** è p &lt;0.005. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53569/53569fig14large.jpg" target="_blank">Fai clic qui per vedere una versione più grande di questa figura.</a> I topi CP si allontanano dal bordo Durante avversione Cliff Il test scogliera avversione si basa sulla paura intrinseca dei topi a girare away da una ripida scogliera e dirigersi verso la sicurezza. Anche se alcuni pazienti in CP hanno difficoltà vestibolari, così come il controllo del motore ridotta, i topi CP non hanno mostrato alcun deficit in questo test.

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.

Una serie di test a motore in neonatale topo modello di paralisi cerebrale

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

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24.0K Views.  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.

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

Making Sense of Listening: The IMAP Test Battery

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the abilities to extract and use the information encoded in the auditory signal. We refer to these as listening skills (or auditory processing AP). Deficits in these skills are associated with delayed language and literacy development, though the nature of the relevant deficits and their causal connection with these delays is hotly debated.
When a child is referred to a health professional with normal hearing and unexplained difficulties in listening, or associated delays in language or literacy development, they should ideally be assessed with a combination of psychoacoustic (AP) tests, suitable for children and for use in a clinic, together with cognitive tests to measure attention, working memory, IQ, and language skills. Such a detailed examination needs to be relatively short and within the technical capability of any suitably qualified professional. Current tests for the presence of AP deficits tend to be poorly constructed and inadequately validated within the normal population. They have little or no reference to the presenting symptoms of the child, and typically include a linguistic component. Poor performance may thus reflect problems with language rather than with AP. To assist in the assessment of children with listening difficulties, pediatric audiologists need a single, standardized child-appropriate test battery based on the use of language-free stimuli.
We present the IMAP test battery which was developed at the MRC Institute of Hearing Research to supplement tests currently used to investigate cases of suspected AP deficits. IMAP assesses a range of relevant auditory and cognitive skills and takes about one hour to complete. It has been standardized in 1500 normally-hearing children from across the UK, aged 6-11 years. Since its development, it has been successfully used in a number of large scale studies both in the UK and the USA. IMAP provides measures for separating out sensory from cognitive contributions to hearing. It further limits confounds due to procedural effects by presenting tests in a child-friendly game-format. Stimulus-generation, management of test protocols and control of test presentation is mediated by the IHR-STAR software platform. This provides a standardized methodology for a range of applications and ensures replicable procedures across testers. IHR-STAR provides a flexible, user-programmable environment that currently has additional applications for hearing screening, mapping cochlear implant electrodes, and academic research or teaching.

A test battery (IMAP) for performing an in-depth assessment of auditory and cognitive abilities contributing to listening skills is described. It is quick to administer, child-friendly and free from linguistic confounds. Stimulus generation and protocol management are controlled via a software platform (IHR-STAR) to ensure replicable procedures.

Making Sense di Ascolto: La batteria di test IMAP

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the ...

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Mouse Model of Middle Cerebral Artery Occlusion

Stroke is the most common fatal neurological disease in the United States 1. The majority of strokes (88%) result from blockage of blood vessels in the brain (ischemic stroke) 2. Since most ischemic strokes (~80%) occur in the territory of middle cerebral artery (MCA) 3, many animal stroke models that have been developed have focused on this artery. The intraluminal monofilament model of middle cerebral artery occlusion (MCAO) involves the insertion of a surgical filament into the external carotid artery and threading it forward into the internal carotid artery (ICA) until the tip occludes the origin of the MCA, resulting in a cessation of blood flow and subsequent brain infarction in the MCA territory 4. The technique can be used to model permanent or transient occlusion 5. If the suture is removed after a certain interval (30 min, 1 h, or 2 h), reperfusion is achieved (transient MCAO); if the filament is left in place (24 h) the procedure is suitable as a model of permanent MCAO. This technique does not require craniectomy, a neurosurgical procedure to remove a portion of skull, which may affect intracranial pressure and temperature 6. It has become the most frequently used method to mimic permanent and transient focal cerebral ischemia in rats and mice 7,8. To evaluate the extent of cerebral infarction, we stain brain slices with 2,3,5-triphenyltetrazolium chloride (TTC) to identify ischemic brain tissue 9. In this video, we demonstrate the MCAO method and the determination of infarct size by TTC staining.

We demonstrate in the video a method for producing a middle cerebral artery occlusion in adult mice using an intraluminal monofilament. We also show how to evaluate the extent of cerebral infarction by 2,3,5-triphenyltetrazolium chloride (TTC) staining.

Modello murino di Mezzo occlusione dell&#39;arteria cerebrale

Stroke is the most common fatal neurological disease in the United States 1. The majority of strokes (88%) result from blockage of blood vessels in the ...

Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient management strategies. Orthotopic mouse models of oral cancer have been developed to facilitate the study of factors that impact invasion and serve as model system for evaluating anti-tumor therapeutics. In these systems, visualization of disseminated tumor cells within oral cavity tissues has typically been conducted by either conventional histology or with in vivo bioluminescent methods. A primary drawback of these techniques is the inherent inability to accurately visualize and quantify early tumor cell invasion arising from the primary site in three dimensions. Here we describe a protocol that combines an established model for squamous cell carcinoma of the tongue (SCOT) with two-photon imaging to allow multi-vectorial visualization of lingual tumor spread. The OSC-19 head and neck tumor cell line was stably engineered to express the F-actin binding peptide LifeAct fused to the mCherry fluorescent protein (LifeAct-mCherry). Fox1nu/nu mice injected with these cells reliably form tumors that allow the tongue to be visualized by ex-vivo application of two-photon microscopy. This technique allows for the orthotopic visualization of the tumor mass and locally invading cells in excised tongues without disruption of the regional tumor microenvironment. In addition, this system allows for the quantification of tumor cell invasion by calculating distances that invaded cells move from the primary tumor site. Overall this procedure provides an enhanced model system for analyzing factors that contribute to SCOT invasion and therapeutic treatments tailored to prevent local invasion and distant metastatic spread. This method also has the potential to be ultimately combined with other imaging modalities in an in vivo setting.

A comprehensive overview of the techniques involved in generating a mouse model of oral cancer and quantitative monitoring of tumor invasion within the tongue through multi-photon microscopy of labeled cells is presented. This system can serve as a useful platform for the molecular assessment and drug efficacy of anti-invasive compounds.

Multi-fotone Imaging di invasione delle cellule tumorali in un modello di mouse ortotopico di carcinoma orale a cellule squamose

Loco-regional invasion of head and neck cancer is linked to metastatic risk and presents a difficult challenge in designing and implementing patient ...

A Swine Model of Neonatal Asphyxia

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, perfusion deficit, hypoxic-ischemic encephalopathy, pulmonary hypertension, vasculopathic enterocolitis, renal failure and thrombo-embolic complications. Animal models are developed to help us understand the patho-physiology and pharmacology of neonatal asphyxia. In comparison to rodents and newborn lambs, the newborn piglet has been proven to be a valuable model. The newborn piglet has several advantages including similar development as that of 36-38 weeks human fetus with comparable body systems, large body size (&tilde;1.5-2 kg at birth) that allows the instrumentation and monitoring of the animal and controls the confounding variables of hypoxia and hemodynamic derangements.
We here describe an experimental protocol to simulate neonatal asphyxia and allow us to examine the systemic and regional hemodynamic changes during the asphyxiating and reoxygenation process as well as the respective effects of interventions. Further, the model has the advantage of studying multi-organ failure or dysfunction simultaneously and the interaction with various body systems. The experimental model is a non-survival procedure that involves the surgical instrumentation of newborn piglets (1-3 day-old and 1.5-2.5 kg weight, mixed breed) to allow the establishment of mechanical ventilation, vascular (arterial and central venous) access and the placement of catheters and flow probes (Transonic Inc.) for the continuously monitoring of intra-vascular pressure and blood flow across different arteries including main pulmonary, common carotid, superior mesenteric and left renal arteries. Using these surgically instrumented piglets, after stabilization for 30-60 minutes as defined by Z&lt;10% variation in hemodynamic parameters and normal blood gases, we commence an experimental protocol of severe hypoxemia which is induced via normocapnic alveolar hypoxia. The piglet is ventilated with 10-15% oxygen by increasing the inhaled concentration of nitrogen gas for 2h, aiming for arterial oxygen saturations of 30-40%. This degree of hypoxemia will produce clinical asphyxia with severe metabolic acidosis, systemic hypotension and cardiogenic shock with hypoperfusion to vital organs. The hypoxia is followed by reoxygenation with 100% oxygen for 0.5h and then 21% oxygen for 3.5h. Pharmacologic interventions can be introduced in due course and their effects investigated in a blinded, block-randomized fashion.

Large animal models have good translational values in the examination of physiology and pharmacology of neonatal asphyxia. Using newborn piglets, we develop an experimental protocol to simulate neonatal asphyxia which has advantages of studying the systemic and regional hemodynamics, oxygen transport with biochemical and pathologic pathways and correlations.

Un modello di asfissia neonatale suina

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, ...

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health.
Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.
Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult 1,2, because oxygen consumption and delivery reach equilibrium after acute transients 3. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) 4,5.
With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

We combined frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation with diffuse correlation spectroscopy measures of cerebral blood flow index to estimate an index of oxygen metabolism. We tested the utility of this measure as a bedside screening tool to evaluate the health and development of the newborn brain.

Non invasiva di misurazione ottica del metabolismo cerebrale ed emodinamica nei neonati

Perinatal brain injury remains a significant cause of infant mortality  and morbidity, but there is not yet an effective bedside tool that can  accurately ...

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.

Un modello di Piglet neonatale Hypoxic-ischemica Encefalopatia

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

Assessment of Perigenital Sensitivity and Prostatic Mast Cell Activation in a Mouse Model of Neonatal Maternal Separation

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has a lifetime prevalence of 14% and is the most common urological diagnosis for men under the age of 50, yet it is the least understood and studied chronic pelvic pain disorder. A significant subset of patients with chronic pelvic pain report having experienced early life stress or abuse, which can markedly affect the functioning and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Mast cell activation, which has been shown to be increased in both urine and expressed prostatic secretions of CP/CPPS patients, is partially regulated by downstream activation of the HPA axis. Neonatal maternal separation (NMS) has been used for over two decades to study the outcomes of early life stress in rodent models, including changes in the HPA axis and visceral sensitivity. Here we provide a detailed protocol for using NMS as a preclinical model of CP/CPPS in male C57BL/6 mice. We describe the methodology for performing NMS, assessing perigenital mechanical allodynia, and histological evidence of mast cell activation. We also provide evidence that early psychological stress can have long-lasting effects on the male urogenital system in mice.

We are measuring perigenital mechanical sensitivity and mast cell activation in the prostate of male C57BL/6 mice that underwent an early life stress paradigm &#8211; neonatal maternal separation, in order to induce a preclinical model of chronic prostatitis/chronic pelvic pain syndrome.

Valutazione della perigenitale Sensibilità e prostatica Mast attivazione delle cellule in un modello murino di Neonatale separazione materna

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has a lifetime prevalence of 14% and is the most common urological diagnosis for men under 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.

Un neonatale mouse Spinal Cord Injury compressione Modello

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

Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and regeneration, and to define new targets for therapeutics. For decades, models of complete heart regeneration existed in amphibians and fish, but a mammalian counterpart was not available. The recent discovery of a postnatal window during which mice possess regenerative capabilities has led to the establishment of a mammalian model of cardiac regeneration. A surgical model of mammalian cardiac regeneration in the neonatal mouse is presented herein. Briefly, postnatal day 1 (P1) mice are anesthetized by isoflurane and placed on an ice pad to induce hypothermia. After the chest is opened, and the left anterior descending coronary artery (LAD) is visualized, a suture is placed around the LAD to inflict myocardial ischemia in the left ventricle. The surgical procedure takes 10-15 min. Visualizing the coronary artery is crucial for accurate suture placement and reproducibility. Myocardial infarction and cardiac dysfunction are confirmed by triphenyl-tetrazolium chloride (TTC) staining and echocardiography, respectively. Complete regeneration 21 days post myocardial infarction is verified by histology. This protocol can be used to as a tool to elucidate mechanisms of mammalian cardiac regeneration after myocardial infarction.

This protocol describes a highly reproducible model of cardiac regeneration by surgical induction of myocardial infarction in the left ventricle of postnatal day 1 mice. The method involves induction of hypothermic anesthesia and ligation of the left anterior descending coronary artery.

Infarto del miocardio in topi neonati, un modello di rigenerazione cardiaca

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and ...

Transient Middle Cerebral Artery Occlusion Model of Neonatal Stroke in P10 Rats

A number of animal models have been used to study hypoxic-ischemic injury, traumatic injury, global hypoxia, or permanent ischemia in both the immature and mature brain. Stroke occurs commonly in the perinatal period in humans, and transient ischemia-reperfusion is the most common form of stroke in neonates. The reperfusion phase is a critical component of injury progression, which occurs over a period of days to weeks, and of the endogenous response to injury. This postnatal day 10 (p10) rat model of transient middle cerebral artery occlusion (tMCAO) creates a unilateral, non-hemorrhagic focal ischemia-reperfusion injury that can be utilized to study the mechanisms of focal injury and repair in the full-term-equivalent brain. The injury pattern that is produced by tMCAO is consistent and highly reproducible and can be confirmed with MRI or histological analyses. The severity of injury can be manipulated through changes in occlusion time and other methods that will be discussed.

Neonatal stroke is a significant cause of early brain injury requiring a translational model with consistent focal injury patterns and high reproducibility in order to enable study. This study describes the detailed surgical procedure for creating a non-hemorrhagic, unilateral focal ischemia-reperfusion injury in full-term-equivalent rodents.

Transient Medio occlusione dell&#39;arteria cerebrale Modello di Stroke neonatale nei ratti P10

A number of animal models have been used to study hypoxic-ischemic injury, traumatic injury, global hypoxia, or permanent ischemia in both the immature ...