Ce travail est financé par la Commission du New Jersey sur la recherche des lésions cérébrales.

<ol>
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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. 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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>

Aucun conflit d&#39;intérêt déclaré.

La méthode présentée ici LFP modèles de nombreux résultats neuropathalogical et comportementaux de légère à modérée lésions cérébrales traumatiques qui est pourquoi il est devenu un modèle animal largement utilisé de TBI. Il ya plusieurs étapes essentielles à considérer en vue d&#39;accroître la validité et la fiabilité de cette technique. Par exemple, il est important que seuls les animaux dont l&#39;intégrité de la durée n&#39;a pas été compromise lors de la craniectomie être soumis à la LFP et utilisées dans l&#39;étude. Par ailleurs, si la craniectomie est occluse par toute colle ou de ciment tels qu&#39;une partie de la durée sous la craniectomie n&#39;est pas exposée à la force de la pression du fluide, l&#39;animal devrait être éliminé de l&#39;étude. Enfin, si le temps réflexe de redressement ou de taux de mortalité n&#39;est pas dans la fourchette souhaitée, l&#39;animal ne doit pas être inclus dans l&#39;étude. L&#39;intensité de l&#39;impulsion de pression peut être augmentée pour générer des blessures plus graves. Comme le montre la figure 1, la configuration de l&#39;appareil LFP est relativement simple et la reproductibilité de la gravité des blessures est maintenu par la surveillance des atmosphères de pression sur l&#39;oscilloscope. La forme lisse de la courbe sur la trace de l&#39;oscilloscope indique qu&#39;il n&#39;ya pas de bulles d&#39;air dans le fluide qui pourrait interférer avec l&#39;induction de la blessure LFP. Une impulsion de test devraient être livrées avant d&#39;induire des blessures et si la trace oscilloscope ne présentent pas une courbe lisse, des bulles d&#39;air doivent être supprimés. La durée de l&#39;impulsion est d&#39;environ 20 ms ce qui représente le temps d&#39;induction mesurée dans les simulations de crash test. Blessures des impulsions plus courtes sont susceptibles de produire des blessures plus focale. Par conséquent, cette durée de modèles pouls humain TCC. Les changements morphologiques et cellulaires suivantes LFP comprennent les dommages physiques aux tissus ainsi que nombre accru d&#39;astrocytes et les macrophages comme l&#39;a montré dans la figure 2. Il est bien établi que l&#39;un des signes caractéristique de blessure est l&#39;hyperplasie des astrocytes et la formation d&#39;une cicatrice gliale. La cicatrice gliale a été montré pour avoir des effets bénéfiques et nuisibles 24. De même, les macrophages sont connus pour s&#39;accumuler dans les différents tissus après une blessure lors de la phase où le processus de guérison commence 25. Ainsi, l&#39;augmentation du nombre de GFAP et MAC1 cellules positives dans les échantillons de LFP par rapport aux contrôles imposture est révélatrice de l&#39;induction de la blessure. L&#39;absence d&#39;expression de ces marqueurs cellulaires spécifiques dans les contrôles de simulacre indique que les manipulations chirurgicales seuls n&#39;ont pas des conséquences négatives sur la santé des tissus du cerveau et que les changements dans l&#39;expression des protéines sont spécifiques au paradigme des blessures. Les conséquences comportementales de LFP douces illustre la figure 3 comprennent les déficits cognitifs et moteurs. Les résultats MWM indiquent que les souris LFP apprennent finalement la tâche, mais à un rythme plus lent que les souris imposture et qu&#39;ils ne se rappellent pas la tâche aussi bien un jour après la formation. Ainsi, même les souris légèrement blessées sont moins efficaces que les souris au simulacre utilisant des indices externes au processus, consolider, et de stocker des informations spatiales, qui doivent être récupérés lors des essais ultérieurs. Autres hippocampique dépendant des tâches cognitives telles que la réaction de peur conditionnée ont été montré pour être altérée dans des souris soumises à LFP 26. Enfin, le plus court temps de latence à tomber par des souris LFP par rapport aux souris imposture dans le paradigme rotarod jusqu&#39;à 3 semaines après une lésion bénigne est un indicateur de déficits dans vestibulomotor intégré et la fonction sensori-motrices. Une blessure plus modérée de révéler des changements plus frappant dans les fonctions cognitives et motrices comme cela a été démontré par d&#39;autres groupes 27-30. En somme, la LFP est un modèle valable pour TBI humaine parce qu&#39;elle remplit plusieurs des critères attendus. LFP donne la validité de construit en ce sens qu&#39;il recrée le processus étiologique qui induisent TCC chez les humains. Plus précisément, la grandeur de la force et le taux de mortalité est semblable à celle qui se produit dans les sports légers et modérés et les blessures liées voiture avec l&#39;avertissement que les interventions de pré-chirurgicale des blessures sont uniques au modèle animal. LFP présente également la validité apparente de cette récapitule LFP nombreux anatomique, biochimique, les effets neuropathologiques et comportementaux observés dans TBI humaine. Il ya deux changements focale et diffuse détecté après la LFP et la latéralisation de l&#39;impact permet de comparer les dommages morphologiques du côté ipsilatéral à la lésion à celle du côté controlatéral. Une mise en garde est que les effets cognitifs et moteurs peuvent être plus subtiles comme un résultat de blesser un seul hémisphère. Enfin, LFP expositions validité prédictive et la fiabilité de la technique LFP permet l&#39;évaluation de diverses manipulations pharmacologiques et génétiques avant ou après l&#39;induction de dommages 20. Variables physiologiques comme la pression sanguine, le pH du sang et du sanggaz devront être mesurés en présence et en absence d&#39;un médicament de test pour déterminer le mécanisme d&#39;action d&#39;un agent thérapeutique. Toutefois, en raison de la nature complexe des conséquences primaires et secondaires du TCC, c&#39;est une tâche difficile d&#39;identifier une seule intervention qui peuvent atténuer tous les symptômes. Un examen ultérieur de la technique de LFP peut être l&#39;utilisation de micro-fluides percussions qui emploie un microprocesseur, un instrument à entraînement pneumatique pour éliminer le besoin pour l&#39;étalonnage de la force délivrée par le pendule et d&#39;éviter les variables opérationnelles telles que les bulles d&#39;air dans le fluide 15 . Toutefois, l&#39;approche standard de LFP a été prouvée par de nombreux chercheurs d&#39;être une technique fiable et simple d&#39;explorer les mécanismes moléculaires sous-tendant les dommages et la récupération après TBI qui conduira à de meilleures interventions et la thérapeutique.

<ul><li> Instrument de l&#39;alignement pour les souris stéréotaxique (Kopf Instruments) </li><li> De gaz d&#39;anesthésie Souris support de la tête (Kopf Instruments) </li><li> Appareil d&#39;anesthésie avec O 2 flush (Parkland scientifique) </li><li> Appareil d&#39;anesthésie avec O2 flush (Parkland scientifique) </li><li> Buprenorphrine (fournitures pour animaux Webster) </li><li> Actualiser Lacri pommade ophtalmique Lube (Fisher) </li><li> La bupivacaïne / marcaïne (fournitures pour animaux Webster) </li><li> Solution de polyvidone iodée (Fisher) </li><li> 20 g 1 ½ &quot;aiguilles (Becton Dickinson) </li><li> Scalpel lame (# 15) et titulaire (Becton Dickinson) </li><li> Pinces Bulldog (Outils Fine Science) </li><li> Outil de soins dentaires ou d&#39;un grattoir d&#39;os (Science Tools Fine) </li><li> Côté saisir pince Dumont # 6 (Outils Fine Science) </li><li> 3mm de diamètre extérieur trépan (Boutique instrumentation pour la recherche, Université de Pennsylvanie) </li><li> Corde de nylon solide (1,7 mm de diamètre, par exemple, la ligne débroussailleuse) </li><li> Super colle gel </li><li> Loctite colle cyanoacrylate (Loctite 444 Tak Pak) (Henkel Corporation) </li><li> Jet liquide acrylique (Butler Schein) </li><li> Perm Reline / réparation de résine (Butler Schein) </li><li> Stockage oscilloscope TDS 1001B, 40 MHz, 500MS / s (Tektronix) </li><li> Inducteur Trauma Capteur de pression Amplificateur (conception et la fabrication, la Virginia Commonwealth University) </li><li> Dispositif de LFP (conception et la fabrication, la Virginia Commonwealth University) </li><li> Haute pression tubes, 41cm de longueur, le volume de 2ml (Baxter) </li><li> 3M Tissu Vetbond adhésif (Fisher) </li></ul>

lateral fluid percussion: model of traumatic brain injury in mice

Une lésion cérébrale traumatique (LCT) de recherche a atteint l&#39;élan renouvelé en raison de la prise de conscience croissante des blessures à la tête, ce qui résulte de la morbidité et la mortalité. Basé sur la nature de la blessure principale suivante TBI, résultat complexe et hétérogène des conséquences secondaires, qui sont suivis par 1,2 les processus régénératifs. Blessures primaires peut être induite par une contusion directe au cerveau à partir fracture du crâne ou de cisaillement et d&#39;étirement du déplacement des tissus du cerveau provoquant en raison du mouvement 3,4. Les hématomes résultant et des lacérations provoquer une réponse vasculaire 3,5, et les dommages morphologiques et fonctionnelles de la substance blanche conduit à des lésions axonales diffuses 6-8. D&#39;autres changements secondaires fréquemment observées dans le cerveau sont l&#39;œdème et l&#39;augmentation de la pression intracrânienne 9. Après TBI il ya des altérations microscopiques dans les voies biochimiques et physiologiques impliquant la libération de neurotransmetteurs excitotoxique, médiateurs immunitaires et les radicaux d&#39;oxygène 10-12, qui a finalement entraîner à long terme de troubles neurologiques 13,14. Ainsi en choisissant des modèles animaux appropriés de TBI qui présentent similaires événements cellulaires et moléculaires dans TBI humains et de rongeurs est essentielle pour l&#39;étude des mécanismes sous-jacents des blessures et de réparation. Différents modèles expérimentaux de TCC ont été développés pour reproduire les aspects de la TCC observés chez les humains, parmi eux trois modèles spécifiques sont largement adaptées pour les rongeurs: la percussion des fluides, l&#39;impact et le poids corticale goutte / effets d&#39;accélération 1. Le dispositif de percussion fluide produit une blessure par une craniectomie en appliquant une impulsion brève pression sur fluides à l&#39;intactes mère. L&#39;impulsion est créé par un pendule frappant le piston d&#39;un réservoir de fluide. La percussion provoque un déplacement du bref et la déformation du tissu neural 1,15. A l&#39;inverse, l&#39;impact des blessures corticales fournit de l&#39;énergie mécanique à la durée intacts via un pendule rigide sous pression pneumatique 16,17. La masse de chute / l&#39;impact du modèle est caractérisé par la chute d&#39;une tige avec une masse spécifique sur le crâne fermé 18. Parmi les modèles TBI, LFP est le modèle le plus établi et couramment utilisés pour évaluer les lésions cérébrales mixtes focale et diffuse 19. Il est reproductible et est standardisé pour permettre la manipulation des paramètres de blessure. Récapitule LFP lésions observées chez les humains, la rendant ainsi cliniquement pertinentes, et permet l&#39;exploration de nouveaux traitements pour la traduction clinique de 20. Nous décrivons le protocole détaillé pour effectuer la procédure LFP chez la souris. La blessure infligée est légère à modérée, avec des régions du cerveau comme le cortex, l&#39;hippocampe et le corps calleux étant les plus vulnérables. Hippocampique et le moteur des tâches d&#39;apprentissage sont explorés suivantes LFP.

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Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

Fluide latérale percussions (LFP), un modèle établi de blessure traumatique du cerveau chez la souris, est démontrée. LFP répond à trois critères principaux pour les modèles animaux: la pertinence de validité, la fiabilité et la clinique. La procédure, composé de craniotomie chirurgicales, la fixation de la plaque tournante suivie par l&#39;induction d&#39;une blessure, résultant en des blessures focale et diffuse, est décrite.

Percussion Fluide latéral: modèle de lésions cérébrales traumatiques chez la souris

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 vues.  University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School. Fluide latérale percussions (LFP), un modèle établi de blessure traumatique du cerveau chez la souris, est démontrée. LFP répond à trois critères principaux pour les modèles animaux: la pertinence de validité, la fiabilité et la clinique. La procédure, composé de craniotomie chirurgicales, la fixation de la plaque tournante suivie par l'induction d'une blessure, résultant en des blessures focale et diffuse, est décrite.

Vidéo: 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 modèle novateur In Vitro de Blast traumatisme crânien

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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Neurosciences

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.

Effets de neurotraumatologie induite par le souffle sur les rongeurs sous pression du milieu des artères cérébrales

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.

Enquêter sur les altérations dans le microbiote de Caecum après une lésion cérébrale traumatique chez les souris

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.

Modèle murine de l'impact cortical contrôlé pour l'induction des dommages traumatiques de cerveau

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.

Modèle à tête fermée contrôlé électromagnétique de lésion cérébrale traumatique légère chez la souris

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.

Évaluation des changements dans la plasticité synaptique à l’aide d’un modèle éveillé de traumatisme crânien traumatique léger

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.

Entretien d’un dispositif de lésion par percussion de fluide latéral

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

Validation de la réponse aux blessures et des évaluations comportementales dans un modèle de rat TCL

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.

Pleins feux sur l’auteur : Faire progresser la recherche sur les lésions cérébrales traumatiques - Un modèle à tête fermée pour une réplication précise et une évaluation rapide 

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.

Modèle de rat de blessure traumatique légère à tête fermée et sa validation

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