Questo lavoro è finanziato dal New Jersey Commissione sulla ricerca Lesione Cerebrale.

<ol>
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S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+impairment+following+closed+head+injury.">Cognitive impairment following closed head injury.</a> Neurol Clin. 10, 879-893 (1992).</li><li>Levin, H. S., Goldstein, F. C., High, W. M., Eisenberg, H. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Disproportionately+severe+memory+deficit+in+relation+to+normal+intellectual+functioning+after+closed+head+injury.">Disproportionately severe memory deficit in relation to normal intellectual functioning after closed head injury.</a> J Neurol Neurosurg Psychiatry. 51, 1294-1301 (1988).</li><li>Kabadi, S. V., Hilton, G. D., Stoica, B. A., Zapple, D. N., Faden, A. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluid-percussion-induced+traumatic+brain+injury+model+in+rats.">Fluid-percussion-induced traumatic brain injury model in rats.</a> Nat Protoc. 5, 1552-1563 (2010).</li><li>Cherian, L., Robertson, C. S., Contant, C. F., Bryan, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lateral+cortical+impact+injury+in+rats:+cerebrovascular+effects+of+varying+depth+of+cortical+deformation+and+impact+velocity.">Lateral cortical impact injury in rats: cerebrovascular effects of varying depth of cortical deformation and impact velocity.</a> J Neurotrauma. 11, 573-585 (1994).</li><li>Dixon, C. E., Clifton, G. L., Lighthall, J. W., Yaghmai, A. A., Hayes, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+controlled+cortical+impact+model+of+traumatic+brain+injury+in+the+rat.">A controlled cortical impact model of traumatic brain injury in the rat.</a> J Neurosci Methods. 39, 253-262 (1991).</li><li>Flierl, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+closed+head+injury+model+induced+by+a+weight-drop+device.">Mouse closed head injury model induced by a weight-drop device.</a> Nat Protoc. 4, 1328-1337 (2009).</li><li>Lifshitz, J., Chen, J., Xu, Z. C., Xu, X. -. M., Zhang, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chapter+32.">Chapter 32.</a> Animal Models of Acute Neurological Injuries. , 369-384 (2008).</li><li>Thompson, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lateral+fluid+percussion+brain+injury:+a+15-year+review+and+evaluation.">Lateral fluid percussion brain injury: a 15-year review and evaluation.</a> J Neurotrauma. 22, 42-75 (2005).</li><li>Hamm, R. J., Pike, B. R., O'Dell, D. M., Lyeth, B. G., Jenkins, L. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+rotarod+test:+an+evaluation+of+its+effectiveness+in+assessing+motor+deficits+following+traumatic+brain+injury.">The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.</a> J Neurotrauma. 11, 187-196 (1994).</li><li>Scherbel, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+acute+and+chronic+responses+of+tumor+necrosis+factor-deficient+mice+to+experimental+brain+injury.">Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury.</a> Proc Natl Acad Sci. 96, 8721-8726 (1999).</li><li>Morris, R. G., Garrud, P., Rawlins, J. N., O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Place+navigation+impaired+in+rats+with+hippocampal+lesions.">Place navigation impaired in rats with hippocampal lesions.</a> Nature. 297, 681-683 (1982).</li><li>Stichel, C. C., Muller, H. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+CNS+lesion+scar:+new+vistas+on+an+old+regeneration+barrier.">The CNS lesion scar: new vistas on an old regeneration barrier.</a> Cell Tissue Res. 294, 1-9 (1998).</li><li>Brechot, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+macrophage+activation+state+protects+tissue+from+necrosis+during+critical+limb+ischemia+in+thrombospondin-1-deficient+mice.">Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice.</a> PLoS One. 3, e3950-e3950 (2008).</li><li>Lifshitz, J., Witgen, B. M., Grady, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+cognitive+impairment+after+lateral+fluid+percussion+brain+injury+recovers+by+1+month:+evaluation+by+conditioned+fear+response.">Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: evaluation by conditioned fear response.</a> Behav Brain Res. 177, 347-357 (2007).</li><li>Thompson, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+evaluation+of+traumatically+brain-injured+rats+using+serial+testing+in+the+Morris+water+maze.">Cognitive evaluation of traumatically brain-injured rats using serial testing in the Morris water maze.</a> Restor Neurol Neurosci. 24, 109-114 (2006).</li><li>Doll, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharyngeal+selective+brain+cooling+improves+neurofunctional+and+neurocognitive+outcome+after+fluid+percussion+brain+injury+in+rats.">Pharyngeal selective brain cooling improves neurofunctional and neurocognitive outcome after fluid percussion brain injury in rats.</a> Journal of neurotrauma. 26, 235-242 (2009).</li><li>Fujimoto, S. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+and+cognitive+function+evaluation+following+experimental+traumatic+brain+injury.">Motor and cognitive function evaluation following experimental traumatic brain injury.</a> Neuroscience and biobehavioral reviews. 28, 365-378 (2004).</li><li>Carbonell, W. S., Maris, D. O., McCall, T., Grady, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adaptation+of+the+fluid+percussion+injury+model+to+the+mouse.">Adaptation of the fluid percussion injury model to the mouse.</a> Journal of neurotrauma. 15, 217-229 (1998).</li></ol>

Nessun conflitto di interessi dichiarati.

Il metodo LFP qui presentati molti modelli degli esiti neuropathalogical e comportamentali di lieve a moderata lesione traumatica cerebrale è per questo che è diventato un modello animale ampiamente utilizzato di trauma cranico. Ci sono diversi punti critici da considerare al fine di aumentare la validità e l&#39;affidabilità di questa tecnica. Per esempio, è importante che solo gli animali in cui l&#39;integrità della dura non è stata compromessa durante il craniectomia essere sottoposto a LFP e usati nello studio. Inoltre, se il craniectomia è occlusa da qualsiasi colla o cemento in modo tale che una parte della dura sotto il craniectomia non è esposto alla forza della pressione del fluido, l&#39;animale deve essere eliminato dallo studio. Infine, se il tempo riflesso di raddrizzamento o tasso di mortalità non è compreso nell&#39;intervallo desiderato, l&#39;animale non devono essere inclusi nello studio. L&#39;intensità della pulsazione pressione può essere aumentata fino a generare le lesioni più gravi. Come mostrato nella Figura 1, la configurazione del dispositivo LFP è relativamente semplice e la riproducibilità del grado di lesione è mantenuta attraverso il monitoraggio delle atmosfere di pressione sul oscilloscopio. La forma morbida della curva sulla traccia oscilloscopio indica che non vi siano bolle d&#39;aria nel liquido che potrebbe interferire con l&#39;induzione della lesione LFP. Un impulso di prova deve essere consegnato prima di indurre lesioni e se la traccia dell&#39;oscilloscopio non presenta una curva dolce, le bolle d&#39;aria devono essere rimosse. La durata dell&#39;impulso è di circa 20 msec, che rappresenta il tempo di induzione misurato in simulazioni di crash test. Lesioni di brevi impulsi sono in grado di produrre lesioni più focali. Pertanto, questa durata di modelli impulso umano trauma cranico. I cambiamenti morfologici e cellulari seguente LFP comprendono danni fisici al tessuto così come aumento del numero di astrociti e macrofagi, come dimostrato nella Figura 2. E &#39;ben noto che uno dei segni di lesione caratteristica è l&#39;iperplasia degli astrociti e la formazione di una cicatrice gliale. La cicatrice gliale ha dimostrato di avere sia effetti benefici e dannosi 24. Allo stesso modo, i macrofagi si accumulano in vari tessuti durante l&#39;infortunio seguente fase in cui il processo di guarigione inizia 25. Così l&#39;aumento del numero di GFAP e MAC1 cellule positive nei campioni LFP relativa ai controlli farsa è indicativo della induzione di lesioni. La mancanza di espressione di tali marcatori cellulari specifici controlli farsa indica che le manipolazioni chirurgiche da soli non hanno conseguenze negative sulla salute del tessuto cerebrale e che i cambiamenti nell&#39;espressione delle proteine ​​sono specifici per il paradigma lesioni. Le conseguenze comportamentali della LFP mite illustrato in Figura 3 sono deficit cognitivi e motori. I risultati MWM indicano che i topi LFP finalmente imparare il compito, ma ad un ritmo più lento rispetto ai topi sham e non mi ricordo il compito e un giorno dopo l&#39;allenamento. Così, anche i topi leggermente feriti sono meno efficienti rispetto ai topi sham a utilizzando i riferimenti esterni al processo, consolidare e conservare l&#39;informazione territoriale, che deve essere recuperato durante le prove successive. Altri compiti cognitivi ippocampo-dipendenti, come risposta alla paura condizionata hanno dimostrato di essere ridotta nei topi sottoposti a LFP 26. Infine, la latenza più breve per cadere dai topi LFP rispetto a topi farsa nel paradigma rotarod fino a 3 settimane dopo la lieve lesione è un indicatore di deficit in vestibulomotor integrato e funzione senso-motoria. Una lesione più moderato avrebbe rivelato i cambiamenti più sorprendenti delle funzioni cognitive e motorie, come è stato dimostrato da altri gruppi 27-30. In sintesi, la LFP è un modello valido per trauma cranico umano perché soddisfa molti dei criteri previsti. LFP fornisce validità di costrutto, in quanto ricrea i processi eziologici che inducono TBI negli esseri umani. In particolare, l&#39;intensità della forza e tasso di mortalità è simile a quello che avviene negli sport lieve e moderata e lesioni legate auto con l&#39;avvertenza che gli interventi chirurgici prima dell&#39;incidente sono unici al modello animale. LFP anche mostre validità faccia che ricapitola LFP molte delle caratteristiche anatomiche, biochimiche, gli effetti neuropatologici e comportamentali osservati in TBI umano. Ci sono sia i cambiamenti focali e diffuse rilevato dopo LFP e la lateralizzazione degli effetti permette di confrontare il danno morfologico sul lato ipsilaterale alla lesione a quella sul lato controlaterale. Un avvertimento è che gli effetti cognitivi e motori possono essere più sottili a causa del ferimento di un solo emisfero. Infine, LFP mostra validità predittiva e l&#39;affidabilità della tecnica LFP consente la valutazione delle varie manipolazioni farmacologiche e genetiche prima o dopo l&#39;induzione di lesioni 20. Variabili fisiologiche come la pressione sanguigna, del pH del sangue e il sanguegas dovrà essere misurata in presenza e in assenza di un farmaco di prova per determinare il meccanismo d&#39;azione di un agente terapeutico. Tuttavia, a causa della complessa natura delle conseguenze primarie e secondarie di TBI, è un compito difficile identificare un singolo intervento in grado di attenuare tutti i sintomi. Una considerazione futuro per la tecnica LFP può essere l&#39;uso di micro-liquido a percussione che si avvale di un microprocessore, strumento ad azionamento pneumatico per eliminare la necessità di calibrare la forza espresso dal pendolo e per evitare variabili operative, come bolle d&#39;aria nel liquido 15 . Tuttavia, l&#39;approccio LFP standard è stato dimostrato da molti ricercatori ad essere una tecnica affidabile e semplice per esplorare i meccanismi molecolari alla base del danno e di recupero dopo TBI che porterà a una migliore interventi e terapie.

<ul><li> Allineamento dello strumento stereotassico per topi (Strumenti Kopf) </li><li> Topo gas testa titolare anestesia (Strumenti Kopf) </li><li> Macchina per anestesia con O 2 a filo (Parkland scientifico) </li><li> Macchina per anestesia con O2 (Parkland scientifico) </li><li> Buprenorphrine (Alimentazione Animale Webster) </li><li> Aggiorna Lacri Lube unguento occhio (Fisher) </li><li> Bupivacaina / Marcaine (Alimentazione Animale Webster) </li><li> Povidone-iodio soluzione (Fisher) </li><li> 20 g 1 ½ &quot;aghi (Becton Dickinson) </li><li> Bisturi lama (# 15) e il supporto (Becton Dickinson) </li><li> Morsetti Bulldog (Strumenti Scienza Fine) </li><li> Strumento dentale o raschietto osseo (Strumenti Scienza Fine) </li><li> Lato cogliere forcipe Dumont # 6 (Strumenti di scienze arti) </li><li> 3 millimetri di diametro esterno trapano (Negozio Strumentazione Research, University of Pennsylvania) </li><li> Cavo di nylon solido (1,7 mm di diametro, ad esempio, erbaccia linea trimmer) </li><li> Super colla gel </li><li> Loctite collante cianoacrilato (Loctite 444 Tak Pak) (Henkel Corporation) </li><li> Getto di liquido acrilico (Butler Schein) </li><li> Perm Reline / riparazione Resina (Butler Schein) </li><li> Stoccaggio Oscilloscopio TDS 1001B, 40 mHz, 500MS / s (Tektronix) </li><li> Trauma Induttore Trasduttore Amplificatore di pressione (progettazione e produzione personalizzati, Virginia Commonwealth University) </li><li> LFP dispositivo (progettazione e produzione personalizzati, Virginia Commonwealth University) </li><li> Tubi ad alta pressione, 41 centimetri di lunghezza, 2 ml di volume (Baxter) </li><li> 3M Vetbond tessuto adesivo (Fisher) </li></ul>

lateral fluid percussion: model of traumatic brain injury in mice

Lesioni traumatiche cerebrali (TBI), la ricerca ha raggiunto slancio rinnovato a causa della crescente consapevolezza di lesioni alla testa, che si traducono in morbilità e mortalità. In base alla natura del danno primario in seguito al trauma cranico, complessi ed eterogenei risultato secondario conseguenze, che sono seguiti da 1,2 processi rigenerativi. Lesione primaria può essere indotta da una contusione diretta al cervello da frattura del cranio o da taglio e stiramento del tessuto che causa lo spostamento del cervello dovute al movimento 3,4. La risultante ematomi e lacerazioni provocare una risposta vascolare 3,5, e il danno morfologico e funzionale della sostanza bianca porta al danno assonale diffuso 6-8. Ulteriori cambiamenti secondari comunemente osservati nel cervello sono edema e aumento della pressione intracranica 9. A seguito di trauma cranico non ci sono alterazioni microscopiche vie biochimiche e fisiologiche che comportano il rilascio di neurotrasmettitori eccitotossico, mediatori immunitari e radicali di ossigeno 10-12, che alla fine provocano disabilità neurologica a lungo termine 13,14. Così la scelta di modelli animali appropriati TBI che presentano simili eventi cellulari e molecolari in TBI umani e roditori è fondamentale per lo studio dei meccanismi alla base della lesione e di riparazione. Vari modelli sperimentali di trauma cranico sono stati sviluppati per riprodurre gli aspetti del trauma cranico osservati negli esseri umani, tra cui tre modelli specifici sono ampiamente adattato per roditori: percussioni fluido, impatto corticale e calo di peso / impatto accelerazione 1. Il dispositivo percussioni fluido produce una ferita attraverso una craniectomia applicando un breve impulso di pressione del fluido al intatto dura. L&#39;impulso è stato creato da un pendolo colpisce il pistone di un serbatoio di liquido. La percussione produce spostamenti brevi e deformazioni del tessuto neurale 1,15. Al contrario, lesioni corticali impatto fornisce energia meccanica al intatta durata attraverso un pendolo rigido sotto pressione pneumatici 16,17. La caduta / impatto modello peso è caratterizzato dalla caduta di una canna con un peso specifico sul cranio chiuso 18. Tra i modelli TBI, LFP è il modello più affermati e comunemente usato per valutare miste danno cerebrale focale e diffuso 19. È riproducibile e standardizzato per consentire la manipolazione dei parametri di lesioni. Ricapitola LFP lesioni osservate negli esseri umani, rendendo così lo clinicamente rilevanti, e permette l&#39;esplorazione di nuove terapie per la traduzione clinica 20. Noi descriviamo il protocollo dettagliato per eseguire procedura LFP nei topi. Il danno inflitto è da lieve a moderata, con le regioni cerebrali come corteccia, ippocampo e del corpo calloso è più vulnerabile. Compiti di apprendimento ippocampale ed il motore sono esplorate le seguenti LFP.

Watch this Scientific Journal Video about Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice at JoVE.com

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Laterale fluido percussioni (LFP), un modello stabilito di lesioni cerebrali traumatiche nei topi, è dimostrato. LFP soddisfa tre criteri principali per i modelli animali: rilevanza validità, l&#39;affidabilità e la clinica. La procedura, che consiste di craniotomia chirurgica, la fissazione del mozzo seguita da induzione di lesioni, con conseguente lesioni focali e diffuse, è descritto.

Fluido laterale Percussioni: Modello delle lesioni cerebrali traumatiche nei topi

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and ...

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40.3K Views.  University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. Laterale fluido percussioni (LFP), un modello stabilito di lesioni cerebrali traumatiche nei topi, è dimostrato. LFP soddisfa tre criteri principali per i modelli animali: rilevanza validità, l'affidabilità e la clinica. La procedura, che consiste di craniotomia chirurgica, la fissazione del mozzo seguita da induzione di lesioni, con conseguente lesioni focali e diffuse, è descritto.

Video: Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

A Novel In Vitro Model of Blast Traumatic Brain Injury

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.

A Novel In Vitro Model of Blast Traumatic Brain Injury

This paper describes a novel model of primary blast traumatic brain injury. A compressed-air driven shock tube is used to expose in vitro mouse hippocampal slice cultures to a single shock wave. This is a simple and rapid protocol generating a reproducible brain tissue injury with a high throughput.

Un modello di romanzo In Vitro di ferita di cervello traumatica di scoppio

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the ...

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Neuroscienze

Effects of Blast-induced Neurotrauma on Pressurized Rodent Middle Cerebral Arteries

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral vascular effects. Impact (i.e., non-blast) traumatic brain injury (TBI) is known to decrease pressure autoregulation in the cerebral vasculature in both humans and experimental animals. The hypothesis that blast-induced traumatic brain injury (bTBI), like impact TBI, results in impaired cerebral vascular reactivity was tested by measuring myogenic dilatory responses to reduced intravascular pressure in rodent middle cerebral arterial (MCA) segments from rats subjected to mild bTBI using an Advanced Blast Simulator (ABS) shock tube. Adult, male Sprague-Dawley rats were anesthetized, intubated, ventilated and prepared for Sham bTBI (identical manipulation and anesthesia except for blast injury) or mild bTBI. Rats were randomly assigned to receive Sham bTBI or mild bTBI followed by sacrifice 30 or 60 min post-injury. Immediately after bTBI, righting reflex (RR) suppression times were assessed, euthanasia at the time points post-injury was completed, the brain was harvested and the individual MCA segments were collected, mounted and pressurized. As the intraluminal pressure perfused through the arterial segments was reduced in 20 mmHg increments from 100 to 20 mmHg, MCA diameters were measured and recorded. With decreasing intraluminal pressure, MCA diameters steadily increased significantly above baseline in the Sham bTBI groups while MCA dilator responses were significantly reduced (p &#60; 0.05) in both bTBI groups as evidenced by the impaired, smaller MCA diameters recorded for the bTBI groups. In addition, RR suppression in the bTBI groups was significantly (p &#60; 0.05) higher than in the Sham bTBI groups. MCA&#39;s collected from the Sham bTBI groups exhibited typical vasodilatory properties to decreases in intraluminal pressure while MCA&#39;s collected following bTBI exhibited significantly impaired myogenic vasodilatory responses to reduced pressure that persisted for at least 60 min after bTBI.

Here, we present a protocol to describe methods for ex vivo vascular reactivity determination following a primary blast traumatic brain injury (bTBI) using isolated, pressurized, rodent middle cerebral arterial (MCA) segments. bTBI induction is accomplished using a shock tube, also known as an Advanced Blast Simulator (ABS) device.

Effetti del Neurotrauma indotta da Blast il roditore pressurizzato Middle arterie cerebrali

Though there have been studies on the histopathological and behavioral effects of blast exposure, fewer have been dedicated to blast&#39;s cerebral ...

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also demonstrate that traumatic brain injuries cause changes to the gut microbiota. However, mechanisms underlying the bidirectional regulation of the brain-gut axis remain unknown. Currently, few models exist for studying the changes in gut microbiota after traumatic brain injury. Therefore, the presented study combines protocols for inducing traumatic brain injury using a lateral fluid percussion device and analysis of caecum samples following injury for investigating alterations in the gut microbiome. Alterations of the gut microbiota composition after traumatic brain injury are determined using 16S-rDNA sequencing. This protocol provides an effective method for studying the relationships between enteric microorganisms and traumatic brain injury.

Presented here is a protocol to induce diffuse traumatic brain injury using a lateral fluid percussion device followed by the collection of the caecum content for gut microbiome analysis.

Indagare sulle alterazioni nel caecum Microbiota dopo una lesione cerebrale traumatica nei topi

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also ...

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the United States. In fact, TBI is a contributing factor to over a third of all injury-related mortality. Nonetheless, the cellular and molecular mechanisms underlying the pathophysiology of TBI are poorly understood. Thus, preclinical models of TBI capable of replicating the injury mechanisms pertinent to TBI in human patients are a critical research need. The controlled cortical impact (CCI) model of TBI utilizes a mechanical device to directly impact the exposed cortex. While no model can full recapitulate the disparate injury patterns and heterogeneous nature of TBI in human patients, CCI is capable of inducing a wide range of clinically applicable TBI. Furthermore, CCI is easily standardized allowing investigators to compare results across experiments as well as across investigative groups. The following protocol is a detailed description of applying a severe CCI with a commercially available impacting device in a murine model of TBI.

Here we describe a protocol for the induction of murine traumatic brain injury via an open-head controlled cortical impact.

Modello Murine di impatto corticale controllato per l'induzione di lesioni cerebrali traumatiche

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the ...

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and understanding the mechanisms of how a TBI alters brain function. The availability of multiple animal models of TBI is necessary to model the different aspects and severities of TBI seen in people. This manuscript describes the use of a midline closed head injury (CHI) to develop a mouse model of mild TBI. The model is considered mild because it does not produce structural brain lesions based on neuroimaging or gross neuronal loss. However, a single impact creates enough pathology that cognitive impairment is measurable at least 1 month after injury. A step-by-step protocol to induce a CHI in mice using a stereotaxically guided electromagnetic impactor is defined in the paper. The benefits of the mild midline CHI model include the reproducibility of the injury-induced changes with low mortality. The model has been temporally characterized up to 1 year after the injury for neuroimaging, neurochemical, neuropathological, and behavioral changes. The model is complementary to open skull models of controlled cortical impact using the same impactor device. Thus, labs can model both mild diffuse TBI and focal moderate-to-severe TBI with the same impactor.

The protocol describes mild traumatic brain injury in a mouse model. In particular, a step-by-step protocol to induce a mild midline closed head injury and the characterization of the animal model is fully explained.

Modello elettromagnetico controllato a testa chiusa di lieve lesione cerebrale traumatica nei topi

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...

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

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

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

Valutazione dei cambiamenti nella plasticità sinaptica utilizzando un modello di trauma cranico chiuso sveglio di lieve lesione cerebrale traumatica

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

Maintenance of a Lateral Fluid Percussion Injury Device

Traumatic brain injury (TBI) accounts for roughly 2.5 million emergency room visits and hospitalizations annually and is a leading cause of death and disability in children and young adults. TBI is caused by a sudden force applied to the head and, to better understand human TBI and its underlying mechanisms, experimental injury models are necessary. Lateral fluid percussion injury (LFPI) is a commonly used injury model due to similarities in the pathological changes found in human TBI compared to LFPI, including hemorrhages, vascular disruption, neurological deficits, and neuron loss. LFPI employs a pendulum and a fluid-filled cylinder, the latter having a moveable piston at one end, and a Luer lock connection to stiff, fluid-filled tubing at the other end. Preparation of the animal involves performing a craniectomy and attaching a Luer hub over the site. The next day, the tubing from the injury device is connected to the Luer hub on the animal's skull and the pendulum is raised to a specified height and released. The impact of the pendulum with the piston generates a pressure pulse which is transmitted to the intact dura mater of the animal via the tubing and produces the experimental TBI. Proper care and maintenance are essential for the LFPI device to function reliably, as the character and severity of the injury can vary greatly depending on the condition of the device. Here, we demonstrate how to properly clean, fill, and assemble the LFPI device, and ensure that it is adequately maintained for optimal results.

Proper care and maintenance are essential for a lateral fluid percussion injury (LFPI) device to function reliably. Here, we demonstrate how to properly clean, fill, and assemble an LFPI device, and ensure that it is adequately maintained for optimal results.

Manutenzione di un dispositivo per lesioni a percussione a fluido laterale

Traumatic brain injury (TBI) accounts for roughly 2.5 million emergency room visits and hospitalizations annually and is a leading cause of death and ...

Convalida della risposta alle lesioni e delle valutazioni comportamentali in un modello di ratto mTBI

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

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

Autore in primo piano: Avanzamento della ricerca sulle lesioni cerebrali traumatiche - Un modello a testa chiusa per una replicazione accurata e una valutazione rapida 

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

Modello di ratto di lesione traumatica lieve a testa chiusa e sua convalida

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